6 July 2018 No. 3912

Scripscrip.pharmaintelligence.informa.com Pharma intelligence | informa Texas would continue to be a key location for the group. It is too early to put a specific valuation on Alcon but the figure being ban- died around is $20-25bn, way below what originally paid, though it should be noted that the Basel-headquartered giant will retain Alcon’s ophthalmology pharma- ceuticals business. The latter unit had 2017 sales of $4.6bn and currently has in the pipeline the po- tential blockbuster . The drug is in development for neovascular age-re- lated macular degeneration and diabetic macular edema. Analysts have responded positively to the spin-off plan, which Novartis expects to be tax neutral. Deutsche Bank issued a note saying that “the split makes sense to a com- bination that made little sense,” adding that “the decoupling puts an end to what was an uncomfortable marriage of two good busi- Novartis Sees The Light And Plumps nesses that, in our view, had limited reason in being together except in a quest for di- versification and earnings bridging through For Alcon Spin-Off patent expiries.” KEVIN GROGAN [email protected] The broker added that stockholders would essentially receive shares in both ot on the heels of divesting its stake vision care (such as contact lenses) have companies “and the deal should allow them in the GlaxoSmithKline PLC con- struggled to grow and it was only from the to better realise the sum of Novartis’ parts Hsumer joint venture, Novartis AG is second half of last year, following heavy in- while allowing greater strategic flexibility to spin off its eye care unit Alcon and focus vestment by its parent, that the Alcon busi- for both management teams.” The analysts on becoming “a leading com- ness began its turnaround. went on to say that “given there was little pany,” in the words of CEO Vas Narasimhan. Narasimhan said in a statement that “Al- overlap between the business functions The Swiss major has completed a stra- con has returned to a position of strength and the carve-out of shared admin services tegic review that examined all options for and it is time to give the business more is largely done, we see only modest addi- Alcon ranging from retention, sale or spin- flexibility to pursue its own growth strat- tional earnings disruption.” off and has now plumped for the latter. The egy as the world’s leading eye care devices PharmaVitae analyst Oliver Spray told board intends to seek shareholder approval company.” When the spin-off is completed, Scrip the decision to spin off Alcon followed for the spin-off at Novartis’ annual general it will create a new -based com- the strategic pathway set out by Narasim- meeting in February next year. pany with more than 20,000 employees and han when he became CEO earlier this year Since splashing out $52bn to buy Alcon around $7bn in sales (2017 figures). “which seeks to focus on cutting-edge ther- apies for oncology and rare diseases.” It will from Nestle SA back in 2011, the group’s Alcon is going to be listed on both the allow Novartis “to focus on the increasingly fit within Novartis has been problematic. Swiss and the New York stock exchanges Its two main sub-divisions of surgical and and Novartis stressed that Fort Worth in CONTINUED ON PAGE 5

BROUGHT TO YOU BY THE EDITORS OF PHARMASIA NEWS, START-UP AND SCRIP INTELLIGENCE

Approval Firsts Private Equity Digs In End Of The Road? Dermira and Array celebrate PE interest apparent in Recordati FDA panel throws doubt on market debuts (p12-13) and Sanofi sales (p4-5) abuse-deterrent opioids (p10-11) IN THIS ISSUE

from the editor [email protected]

With Novartis having decided finally to sell Alcon, ques- light on the burden of in workplaces by put- tions arise again about the future of Sandoz. CEO Vas ting numbers of the productivity cost of the disease. Narasimhan acknowledges that the generics business Still, this kind of data doesn’t get the best reception faces price erosion in the US and his team is working in traditional health technology assessments. If pharma out how to keep it competitive (see cover story). As our is frequently frustrated in getting healthcare payers to story on the 2017 rankings of the world’s top generics acknowledge the broader value to society of their medi- firms on p9 shows, it is not the only one struggling in cine, then it makes sense to take the message where the the US. costs of not treating the disease are felt more acutely. In Meanwhile, Novartis’ branded pharma business is an Novartis/’s migraine case, this means engaging enthusiastic innovator in value negotiation. It and part- with employers by offering workplace programs that ner Amgen recently presented a migraine study at the help cut the number of days people take off work. American Headache Society’s annual meeting which It’s not stated explicitly, but getting employers on side provides a concrete example of how pharma companies may well help Novartis and Amgen sell more of their could gain a better reception for their value proposi- new migraine drug Aimovig. Which should help offset tion. In short, Novartis backed a patient study that shed its competitive price.

LEADERSHIP ADVERTISING DESIGN Phil Jarvis, Mike Ward, Christopher Keeling Paul Wilkinson Karen Coleman DESIGN SUPERVISOR SUBSCRIPTIONS Gayle Rembold Furbert Scrip Dan Simmons, Ewan Ritchie, Shinbo Hidenaga

EDITORS IN CHIEF John Davis EDITORIAL OFFICE Ian Haydock (Asia) Kevin Grogan Christchurch Court Eleanor Malone (Europe) Ian Schofield 10-15 Newgate Street Denise Peterson (US) Vibha Sharma London, EC1A 7AZ Joanne Shorthouse CUSTOMER SERVICES Sten Stovall EXECUTIVE EDITORS US Toll-Free: +1 888 670 8900 COMMERCIAL US Toll: +1 908 547 2200 Alexandra Shimmings (Europe) US UK & Europe: +44 (20) 337 73737 Mary Jo Laffler (US) Michael Cipriano Australia: +61 2 8705 6907 Derrick Gingery POLICY AND REGULATORY Japan: +81 3 6273 4260 Joseph Haas Maureen Kenny (Europe) Email: clientservices@ Emily Hayes Nielsen Hobbs (US) pharma.informa.com Mandy Jackson ASIA Cathy Kelly Jessica Merrill TO SUBSCRIBE, VISIT Anju Ghangurde scrip.pharmaintelligence.informa.com Jung Won Shin Brenda Sandburg TO ADVERTISE, CONTACT Brian Yang Bridget Silverman Sue Sutter [email protected]

EUROPE All stock images in this publication Neena Brizmohun courtesy of www.shutterstock.com Francesca Bruce unless otherwise stated

Scrip is published by Informa UK Limited. ©Informa UK Ltd 2018: All rights reserved. ISSN 0143 7690.

2 | Scrip | 6 July 2018 © Informa UK Ltd 2018 AbbVie To Take Off? AstraZeneca’s Oncology Promises Generics Firms Rankings

20 16 20 9

exclusive online content inside: Aquinox, Astellas Mull Options As Rosiptor Fails COVER / Novartis Sees The Light And Plumps For Alcon Spin-Off https://bit.ly/2KIt5fv 4 Recordati Founding Family Sells €3bn Stake Astellas’ late-stage bet on Aquinox’s urology drug now looks highly unlikely to pay off following the molecule’s “definitive” failure in a Phase III trial, which is also forcing the originator to 5 Sanofi Finalizes Zentiva Sale consider its business and R&D options. 6 Roivant Cuts Jobs, Reallocates Staff Roche’s IMpassion130 Is First Positive Phase III Immunotherapy Study In Triple Negative Breast Cancer 7 Pursues ‘Market First’ Playbook, Partners Lupin https://bit.ly/2zgNUh5 Phase III IMpassion130 study showed Tecentriq plus Abraxane 8 Ups Samsung Bioepis Stake In $700m Bet significantly reduced the risk of disease worsening or death in On Biosimilars people with metastatic triple negative breast cancer. 9 Teva Retains Top Slot As Industry Faces US Pushback Lilly’s Taltz Gets Closer To A Level Playing Field With Novartis’ Cosentyx 9 Akebia And Keryx To Merge https://bit.ly/2tUkMGY Lilly reported positive results for Taltz in a second Phase III study 10 PTI’s Remoxy: Negative FDA Panel Review May Be The End in ankylosing spondylitis and plans to file for FDA approval this Of Abuse-Deterrent Opioid’s Road year, which would give the IL-17A inhibitor a label similar to its rival Cosentyx, for which Novartis is working hard to build, 12 Array Raring To Go With First Approval: Mektovi/Braftovi maintain and grow market share. 13 Dermira Wins First FDA Approval, For Qbrexza Celgene Notches A Needed Win As Acceleron- Partnered Luspatercept Succeeds In MDS 14 GW’s Epidiolex Approval Encouraging For Pharma-Grade https://bit.ly/2tVsEY6 Cannabinoid Pipeline Celgene delivers positive top-line Phase III results for a key pipeline drug as luspatercept reduces the need for blood 15 Cablivi CHMP Backing Helps Validate Sanofi’s €3.9bn transfusions in patients with myelodysplastic syndromes. Ablynx Purchase Partner Acceleron’s stock soars ahead of a detailed data presentation later this year. 16 AbbVie To Take Flight From Galapagos As Deal Watch: Amazon Moves Into Rx Services With PELICAN Flounders? Acquisition Of PillPack 18 Novo Nordisk Touts First-Line Potential For Oral https://bit.ly/2IPHHIb Celgene makes play into RNA-expression correction via 20 AstraZeneca Looks To Deliver On Its Promises In Oncology neuroscience partnership and equity investment with Skyhawk. Novartis’ Sandoz agreed to commercialize Adamis’ Symjepi, a competitor to EpiPen, in the US. 22 Pipeline Watch

Finance Watch: Is The IPO Boom Making Anyone 23 Appointments Nervous Yet? https://bit.ly/2KIJmkN Public Company Edition: Is the IPO bubble getting ready to burst? It’s anybody’s guess, but biopharma companies are forging ahead, having launched 11 first-time offerings during the past week and a half. Also, Heron leads recent follow-on @PharmaScrip /scripintelligence offerings with a $200m stock sale to fund what may soon be its third commercial product. /scripintelligence /scripintelligence

scrip.pharmaintelligence.informa.com 6 July 2018 | Scrip | 3 COMPANIES

Recordati Founding Family Sells €3bn Stake ELEANOR MALONE [email protected]

he Recordati family has sold the holding company that owns CVC invests across a range of sectors, and is already active in health- the majority stake in the Italian pharma firm that bears its care with investments in medical providers. It also completed the T name to a consortium of private equity funds led by CVC. purchase of the women’s health business of Teva Pharmaceutical The latter is paying €3.03bn for FIMEI SpA, which owns 51.8% of Industries Ltd. in Feb. 2018, forming London-based Theramex. the company. The value of the deal is almost 18% below the closing Private equity (PE) firms are showing increasing interest in the price of Recordati Industria Chimica & Farmaceutica SPA’s shares life sciences space, with several investments in outsourced clinical on the Milan stock market prior to the announcement. However, services businesses and less frequently pharma businesses them- the share price had been pushed up in recent weeks by rumors of selves. Martin Gouldstone, partner at corporate advisory firm Results a pending buyout valued at up to €9bn, and general stock market Healthcare, flagged up at a recent event focused on private equity turbulence in Italy. activity in the healthcare/biotech/medtech space the factors that are CEO Andrea Recordati has invested alongside the private equity driving deals, including the large amounts of capital PE has built up. partners, and will retain his position at the firm, as will incumbent He noted that the scarcity value of suitable investment opportuni- managing director and chief financial officer Fritz Squindo. ties in the space, new market entrants in PE and competition from CVC said it would be looking to expanding Recordati’s rare disease “strategics” (ie, other companies in the sector looking to consolidate) business, helped by its own “expertise and global healthcare net- were driving a boom in PE investment in life sciences. work” to “build a global leader in the industry.” Gouldstone’s fellow partner Kevin Bottomley underscored that for Recordati reported first-quarter revenue growth of 7.2% to his clients, PE can prove to be the “best buyers, who will invest in the €366.5m on May 8, and net income growth of 10.3% to €86.6m. It business going forward.” Gouldstone noted that these days, “PE can reiterated a forecast of 2018 sales of €1.35-1.37bn and net income of enable management to retain some control and grow the business.” €310-315m, up from €1.29bn and €289m respectively in 2017. EBIT- He doesn’t see PE activity in the health space declining for some DA was €455m in 2017. In recent years the company has looked to time because firms have raised “significant funds” and are “expanding diversify away from a focus on primary care into the potentially more geographically, trying to capture opportunity.” lucrative orphan drug and specialty care space. Another private equity source said that their firm was investing in However, it suffered a setback recently when partner Erytech the healthcare space with an interest in “commercial risk rather than Pharma SA announced it was pulling its European marketing autho- development risk.” They highlighted as attractive targets for PE old rization application for Graspa (eryaspase) for acute lymphoblastic drugs with potential for future commercial growth to be optimized, leukemia because of the rapid pace of improvements in treatment and companies with two or three products in a specialty pharma options for the disease, which was already a small market opportu- niche looking to expand their portfolio. nity. The product, which described in a May 9 note as Sanofi only last week finalized the sale of its generics business Recordati’s “most significant late-stage R&D asset,” had been expect- Zentiva BV to PE group Advent, for €1.9bn. ed to win approval in Europe in the fourth quarter. Last year, German pharma Stada Arzneimittel AG was sold to PE buyers Bain Capital and Cinven for about €5.4bn. STOCK EXCHANGE LISTING EXPECTED TO STAY And contract research organization Parexel International Once the FIMEI acquisition has closed, the CVC Fund VII-led consor- Corp. was bought by Pamplona Capital Management in 2017’s other tium will make a tender offer to the remaining minority shareholders, biggest PE healthcare buyout, worth $5bn including debt. as required by Italian law, at €28.00 per share in cash. This is the im- The Recordati/CVC deal was valued at 13.3 X EBITDA, giving it the plied value of the shares under the holding company buy-out, which highest multiple of the recent specialty pharma PE buy-outs. Zentiva would give Recordati a 100% equity value of €5.86bn. and Stada were around 12.5-13 X EBITDA. The investors however expect Recordati to remain listed on the According to Tommy Erdei, joint global head of pharma and life Italian stock exchange. Its shares only briefly fell below €28.00 in late sciences at Jefferies, which acted as financial adviser to the Recor- March and otherwise have traded higher than that since February dati family on the agreement, the increasing participation of PE in 2017, peaking at €40.60 in November 2017 and closing at €34.06 on pharma deal-making reflects the changing dynamics in the specialty June 29, 2018, the last trading day before the deal was announced. pharma subsector: where once there were strategic firms like Vale- The shares opened down 17.4% at €28.12 after the deal was an- ant Pharmaceuticals International Inc., Teva, Mylan NV and Meda nounced on July 2. very actively pursuing significant M&A tactics, “those strategics are The €3.03bn will include a €2.3bn cash payment and €750m in currently more internally focused, after a spree of deals allowing subordinated long-term debt securities to the Recordati family. Oth- these PE opportunities,” and PE is now less likely to be “trumped” by er investors in the consortium include PSP Investments (the Cana- such companies. dian public sector pension investment manager) and StepStone. He said that as funds got bigger and found it challenging to find Andrea Recordati took over as CEO of the firm, which was founded large enough opportunities to put their equity to work, the “very in 1926, following the death of his step-brother Giovanni Recordati natural buy and build strategy” that works better in pharma than in in 2016. Giovanni’s brother Alberto Recordati is current chairman but many other sectors made it attractive. it is likely CVC will nominate a successor once the transaction closes. Published online 2 July 2018

4 | Scrip | 6 July 2018 © Informa UK Ltd 2018 HEADLINE NEWS/COMPANIES

CONTINUED FROM COVER competitive area of digital technologies which companies like Roche are already us- Sanofi Finalizes Zentiva Sale ing to augment their cancer therapies,” he KEVIN GROGAN [email protected] said, adding that the group was also increas- ing its exposure to gene and cell therapies lmost a decade after the purchase of ing M&A. Sanofi sees consumer healthcare “in an attempt to stake a leadership position Zentiva BV, Sanofi has now finished as core, with the Paris-headquartered big in this growing market.” Anegotiations with the private equity pharma exchanging its animal health busi- In January, Novartis gained European firm Advent International for the €1.9bn sale ness for Boehringer Ingelheim GMBH’s rights to Spark Therapeutics Inc.’s gene of its European generics business, as the consumer health portfolio last year while therapy Luxturna (voretigene neparvovec) French drugmaker continues to reshape its 2018 has already seen the company splash in Europe, and then in April spent $8.7bn on operations and focus on its newer purchases out €16bn on the hemophilia specialist Bio- Bioverativ Inc. and Ablynx NV. verativ and the nanobody platform Belgian the gene therapy biotech AveXis Inc.. At the Sanofi and Advent have now signed a firm Ablynx. beginning of this year, it also completed the share purchase agreement for the sale of Selling Zentiva adds €1.9bn to Sanofi’s war- $3.9bn acquisition of French oncology spe- Zentiva, having announced April 17 that chest but observers will probably have to wait cialist Advanced Accelerator Applications. they had entered into exclusive talks. In a until July 31 when the company reveals its statement, the companies said that the second-quarter financials for clues as to what $5BN SHARE BUYBACK, signing marked “a critical step on the way the money will be spent on. As to what those SANDOZ SAFE FOR NOW to the closing of the deal,” and the transfer figures will look like, analysts at Deutsche Bank The focus on innovative pharma drove No- was anticipated during the fourth quarter recently issued an investor note saying that vartis’ decision in March to sell its stake in of 2018. “we expect 2Q to be another tough quarter in a consumer healthcare joint venture with Sanofi bought Zentiva for €1.8bn in 2009, a turnaround year,” and claiming that the sec- GSK. That deal brought in $13bn and pro- a year that also saw the firm acquire Medley, ond quarter “is a risk event that needs to pass ceeds from that transaction will be used to Brazil’s largest generics manufacturers and before investors could become increasingly fund a share repurchase program of up to Laboratorios Kendrick, one of Mexico’s lead- comfortable with Sanofi’s then-likely positive $5bn to be executed by the end of 2019. ing generics companies. Although only get- earnings momentum.” Narasimhan said the share buyback “is ting a bit more than it paid for Zentiva, the The broker is forecasting sales of €8.3bn. fully aligned with our strategic capital allo- Czech-headquartered business has made Currency “will be a clear negative” but a full cation priorities, reflects our strict financial solid contributions to Sanofi’s coffers, with quarter of Bioverativ sales, from Eloctate (re- discipline and our confidence in future top- sales last year coming in at around €760m. combinant Factor VIII) for hemophilia A and line growth and margin expansion.” Advent is getting its hands on a company Alprolix (recombinant Factor IX) for hemo- The Alcon spin-off plans and the exit which claims on its website to reach over 40 philia B, “will be a tailwind.” from consumer health have again led some million patients in 25 European countries, Next week will also see the official arrival observers to wonder whether the next di- “operating throughout a large marketplace of John Reed, former global head of pharma vestment by Novartis could be the gener- with attractive levels of both short- and Research & Early Development (pRED) at ics business Sandoz, which has struggled mid-term growth outlook.” Zentiva says that Roche. who will join Sanofi as the head of in US markets in recent months. Spray told it “stands apart with the expertise and agil- global R&D effective July 1, succeeding the Scrip that the PharmaVitae team very much ity to tailor customer-centric solutions in the company’s long-time research chief Elias doubted such a move would take place, say- three European generics market archetypes Zerhouni. Reed actually joined Sanofi on ing “we believe that Novartis will opt instead (, physician and tender/wholesal- April 30 to help ensure a smooth transition to follow the industry-wide trend of focusing er)” and its “flexible manufacturing facilities and it will be interesting to see which areas on products that are insulated from pricing in Prague and Bucharest work with partners he focuses on. Some observers believe that pressure and towards more complex and ex- to produce and distribute more than 350 Sanofi may look to strengthen in oncology, pensive alternatives.” He added that the suc- million packs each year.” a field it has fallen behind in of late, although cess of Sandoz would also hinge on strong Announcing plans to sell in April, Sanofi it has high hopes for cemiplimab, its Re- launches of drugs in its biosimilar program, CEO Olivier Brandicourt described Zentiva generon Pharmaceuticals Inc.-partnered which currently consists of eight products. as “a robust business with a highly talented anti-PD-1 candidate which has been filed On a conference call, Narasimhan said workforce and we believe it has demon- on both sides of the Atlantic for cutaneous that Sandoz was a core business, noting that strated its potential for growth.” However, a squamous cell carcinoma (CSCC). it was the number two generics company comprehensive review of strategic options It seems that Sanofi’s fondness for ge- in the world, and arguably number one in has revealed that a European generics busi- nerics will continue to dwindle but private biosimilars. However, he acknowledged the ness is not part of the turnaround Brandi- equity groups like Advent see value in the price erosion problems the unit was facing court has been directing since taking over sector. The Zentiva deal comes a year after in the US and said Novartis was evaluating the helm in February 2015. the German generics and OTC company, how to optimize Sandoz and ensure that it Charged with tackling the challenge of Stada Arzneimittel AG, was sold to two such stayed competitive. dealing with the decline of its diabetes fran- companies, Bain and Cinven, for €5.4bn. Published online 30 June 2018 chise, the CEO has not been shy in embrac- Published online 28 June 2018 scrip.pharmaintelligence.informa.com 6 July 2018 | Scrip | 5 COMPANIES

Roivant Cuts Jobs, Reallocates Staff MANDY JACKSON [email protected]

oivant Sciences GMBH’s big star Head of Special Projects Benjamin Zimmer preclinical assets is notable, since Roivant has Axovant Sciences Ltd. failed the first will be president of Roivant Health. The unit focused since its launch in 2014 on acquiring Rbig test of the parent company’s risk- will focus on new biopharma companies clinical drug candidates that have been de- reducing strategy, but a reorganization an- targeting emerging markets, such as the prioritized by big pharma and other estab- nounced on June 26 is meant to strengthen previously launched Sinovant Sciences lished firms. The strategy change gives Roi- and launch other Roivant subsidiaries, with Ltd., and subsidiaries with technology vant an opportunity to license more assets different programs pushed into the spotlight. aimed at improving drug development and at lower costs, since the owners of preclini- The organizational changes were an- commercialization, such as the Zimmer-cre- cal development programs and technology nounced just two weeks before the first- ated company Datavant Sciences. platforms won’t have invested as much of ever Roivant Pipeline Day scheduled for July Newly created Altavant, which is focused their own capital as big pharma partners put 10 where the parent company will show- on “next-generation drug development,” will into discontinued clinical-stage assets. case its clinical programs and subsidiaries. advance RVT-1201 for pulmonary arterial Roivant’s investors may appreciate such The reorganization will split Roivant into hypertension (PAH) and other indications. frugal spending, since the company so far has two business units focused separately on Roivant declined to say where the drug was made big bets without generating sizeable company creation and emerging markets, licensed from, how it works and what stage returns. Barely a month and a half after Roivant spin out a new subsidiary – or Vant – called of development it’s in, but said that it plans raised $1.1bn in private equity to fund new Altavant Sciences, shift certain Roivant to share more information during its Pipe- company formation in August, Axovant an- employees to its various Vants, and cut over- line Day next month. nounced the Phase III failure of intepirdine in all headcount by less than 10%. Altavant is led by CEO William Symonds, Alzheimer’s, which cut the neurology-focused Roivant was designed to centralize ad- who has been with Roivant since 2014, subsidiary’s value by 74% in September. ministrative and other costs for subsid- serving most recently as chief develop- Axovant discontinued development of iaries created to rapidly advance specific ment officer. Symonds previously oversaw intepirdine following the failed Phase IIb drug development programs. If an asset development of hepatitis C blockbusters HEADWAY study in dementia with Lewy succeeded, rewards would flow back to Sovaldi (sofosbuvir) and Harvoni (ledipasvir/ bodies in January. Then Axovant lost its re- the parent, but if it failed the subsidiary sofosbuvir) at Pharmasset Inc. and Gilead cently hired, high-profile CEO – Medivation would take most of the hit. But job cuts Sciences Inc. Inc. founder and former CEO David Hung – after the Phase III failure of intepirdine in and hinted at additional job cuts in February. Alzheimer’s disease last year apparently IN-LICENSING FOCUS NOW weren’t limited to Axovant, since Roi- Roivant founder and CEO Vivek Ramaswamy NEXT PHASE III MILESTONES vant’s reorganization will put 67 people said in the announcement about the com- With intepirdine’s failure, the most advanced out of work. pany’s reorganization that he is “excited to drug candidates in Roivant’s portfolio are elevate several of Roivant’s talented leaders” being developed by Myovant, Enzyvant and TWO NEW BUSINESS UNITS and noted that going forward the company Urovant – and possibly Altavant if RVT-1201 Roivant Chief Business Officer Myukh will not focus exclusively on in-licensing is in Phase III. Sukhatme is now president of the new busi- drug candidates already in the clinic. Enzyvant licensed global rights to RVT- ness unit Roivant Pharma, which will focus “Going forward, we will expand the scope 802, a Phase III tissue-based therapy for the on biopharmaceutical company creation in of our focus to include the advancement of rare congenital immunodeficiency disease new therapeutic areas. Sukhatme already potentially transformative assets into clini- complete DiGeorge syndrome (cDGS) from oversees Roivant’s in-licensing activities, but cal development, even if they are at earlier Duke University early last year. Enzyvant also will lead company formation around as- stages of development than much of our intends to submit a biologic license appli- sets that don’t fit into existing subsidiaries. pipeline to date,” Ramaswamy said. cation (BLA) based on the Duke-generated Vants to date include neurology-focused Roivant framed its reorganization as one Phase III data to the US FDA during the first Axovant, women’s health firm Myovant that allows the company to accelerate new half of 2018 – a milestone that may be an- Sciences Ltd., dermatology specialist Der- company formation and pursue earlier- nounced at Roivant’s Pipeline Day on July 10. mavant Sciences Ltd., the rare disease firm stage science. However, the changes also Also in Phase III, Myovant is Roivant’s only Enzyvant Sciences Ltd., urology drug de- will move some of the parent company’s other company besides Axovant that is veloper Urovant Sciences Ltd., RNA-based employees into existing subsidiaries “to fur- publicly traded. However, Ramaswamy has therapeutics joint venture Genevant Scienc- ther the advancement of their pipelines and said that Roivant does not intend to pursue es Ltd., and Metavant Sciences Ltd. with an ensure greater organizational autonomy.” any other initial public offerings for its sub- interest in cardiometabolic diseases. Roivant said this led to a reduction in head- sidiaries, because it wants the firms to focus Two other existing Vants appear to be- count of less than 10%; a spokesman con- on drug development, not the responsibili- long under Roivant’s other newly created firmed that 67 employees lost their jobs. ties that come with being a public compa- business unit, Roivant Health. Roivant’s The company’s decision to now consider ny. Even so, with a closing price of $24.05

6 | Scrip | 6 July 2018 © Informa UK Ltd 2018 COMPANIES

per share on June 26, Myovant’s stock is receptor antagonist for women with uterine based on positive Phase IIb results gener- trading near its one-year high of $25.54. fibroids or endometriosis. ated by Merck. Those data give vibegron a The company’s stock is rising due to op- AbbVie’s elagolix may get there first, since 66% likelihood of FDA approval – 4% above timism for its lead drug candidate relugolix, it is under FDA review for endometriosis average – according to Biomedtracker. which was bolstered by Phase III data from and in Phase III for uterine fibroids. However, Also, Sinovant acquired rights in China Takeda Pharmaceutical Co. Ltd. in Japa- both products may have competition from and a few other Asian territories at the nese women with uterine fibroids in Octo- PLC’s selective estrogen receptor end of March for Nabriva Therapeutics ber. Myovant is expected to report results modulator (SERM) Esmya (ulipristal), which PLC’s anti-infective lefamulin after the from its international Phase III studies for the FDA is reviewing for the treatment of successful completion of Nabriva’s first relugolix in uterine fibroids and endome- uterine fibroids, though safety concerns Phase III international study for the drug. triosis in 2019. pushed back an approval decision. There were safety concerns in a second Roivant founded Myovant in 2016 when Further behind Myovant within Roivant’s Phase III trial that also was deemed a suc- it licensed rights to relugolix from Takeda portfolio, Urovant launched a year ago when cess, but Nabriva intends to seek FDA outside of Japan and certain Asian coun- Roivant licensed the oral beta-3-adener- approval based on both studies. Roivant tries. Now, Myovant is in a race with AbbVie gic agonist vibegron for overactive blad- may update Sinovant’s plans for lefamulin Inc. to win the first FDA approval for an oral der (OAB) from Merck & Co. Inc. The com- in China on July 10. gonadotropin-releasing hormone (GnRH) pany initiated a Phase III OAB study in March Published online 26 June 2018 Mylan Pursues ‘Market First’ Playbook, Partners Lupin ANJU GHANGURDE [email protected]

ylan NV is leap-frogging plans for ucts alongside existing alliances. Mylan initial caution with biosimilars to translate into biosimilar etanercept in certain president Rajiv Malik said the deal with Lupin relatively slow uptake of biosimilar etanercept, Mkey markets via an alliance with was yet another positive step to bring key bi- with use limited primarily to new patients. Lupin, along the lines of similar efforts for osimilars like etanercept to patients around “In the long term, growing confidence biosimilar adalimumab earlier this year. the world “as quickly as possible”. Biocon in biosimilars driven by increasing familiar- The US firm has inked a deal to commer- Ltd.’s etanercept is in the preclinical stage, a ity and post-marketing data, in conjunction cialize Lupin Ltd.’s biosimilar version to Am- May 2018 company presentation indicated. with further expected decreases in the cost gen Inc./ Inc.’s Enbrel (etanercept) in In April this year, Mylan acquired com- of biosimilar etanercept, will lead to greater Europe, Australia, New Zealand, Latin Ameri- mercial rights in Europe to Fujifilm Kyowa erosion of Enbrel’s patient share to biosimi- ca, Africa and most markets throughout Asia. Kirin Biologics Co. Ltd.’s biosimilar adalim- lar etanercept,” Datamonitor Healthcare said Lupin will receive an upfront payment of umab, with an eye on early market entry; it in a recent report. The report forecasts En- $15m and is entitled to potential commer- also has an ongoing program for biosimilar brel will lose up to 55% of its patient share cial milestones together with an equal share adalimumab with partner Biocon. to biosimilar etanercept in Europe. in net profits of the product. Mylan president Rajiv Malik at the time Meanwhile, Biocon said that it would Lupin’s CEO, Vinita Gupta, said that Mylan maintained that “nothing is wrong with “benefit” from the opportunity to “acceler- was “well-positioned” to commercialize the the Biocon partnership” but the market ate commercialization” of etanercept under firm’s etanercept biosimilar given its signifi- comes first. Mylan’s latest deal with Lupin. cant expertise and global infrastructure. “And when we realize that we will not be “Biocon clarifies that it retains its eco- The deal with Mylan marks Lupin’s second in time for Europe for market formation with nomic interest in this arrangement vis-à-vis alliance on the trot for the biosimilar etaner- our biosimilar to Humira, we had to make Mylan in accordance with its existing collab- cept, developed under a JV with Yoshindo. the call in favour of the FKB product. We are oration agreement,” the company informed Lupin recently firmed up a deal with Nichi- very happy and that we could find an op- the Bombay Stock Exchange June 28. It had Iko Pharmaceutical Co. Ltd. for its distribu- portunity to be in the market at the time of maintained a similar position at the time of tion, promotion and sale in Japan. the market formation,” Malik said at the in- Mylan’s deal with FKB for adalimumab. Lupin’s etanercept filing in Japan follows a vestor meet April 11. Biocon, however, also has entered into successful Phase III study that included more In the case of biosimilar etanercept, Bene- an alliance with Sandoz for developing than 500 patients with RA in 11 countries; pali (Biogen/Merck & Co/Samsung Bio- and commercializing the next-generation the partners will launch the product there epis) has already been launched in certain of biosimilars. following approval from the Pharmaceuti- EU markets; Sandoz International GMBH’s It’s not immediately clear if Mylan could cals and Medical Devices Agency (PMDA). biosimilar etanercept Erelzi was approved by be Lupin’s logical partner for the US too for Mylan’s latest alliance suggests that get- the EMA in June 2017. Enbrel reported global entanercept. ting the market timing right is a priority for sales of about $11.6bn for the 12 months end- Lupin anticipates a US filing for etaner- the US firm’s overall biosimilar play and it ed December 2017. In Europe, Informa’s Data- cept in Q4 FY20. won’t shy away from deal-making for prod- monitor Healthcare expects rheumatologists’ Published online 29 June 2018

scrip.pharmaintelligence.informa.com 6 July 2018 | Scrip | 7 BIOSIMILARS

Biogen Ups Samsung Bioepis Stake In $700m Bet On Biosimilars JUNG WON SHIN [email protected]

iogen Inc. has exercised an option to purchase additional It is unclear how or how much Biogen’s increased stake may affect shares in Samsung Bioepis Co. Ltd., a joint venture estab- the authorities’ probe. Some local media have speculated it is likely Blished in 2012 by Samsung BioLogics and the US firm, in a to work in favor of Samsung BioLogics, while others say that the in- move that will raise its stake to nearly 50% and allow Biogen to jointly vestigation will focus more on whether Samsung has appropriately run the biosimilars venture. reflected the JV in its accounting rather than whether Biogen will ex- Under the terms of the original joint venture agreement, Biogen ercise its option or not. will pay Samsung BioLogics about $700m for the option shares, in- Samsung BioLogics shares gained 2.1% on the main Kospi market creasing Biogen’s ownership in Samsung Bioepis from about 5.4% to on June 29 on the expected hefty cash inflow from Biogen, a transac- about 49.9%. The completion of the share purchase remains subject tion set to lower Samsung BioLogics’s debt-to-equity ratio to 35.2% to certain regulatory conditions but is expected to close in the sec- from 88.6%, the Korean company said. ond half of 2018. The exact share purchase price will depend on the timing of the clos- ACCOUNTING PRACTICES UNDER SCRUTINY ing and foreign currency exchange rates at that time, Biogen said in a South Korea’s Securities and Futures Commission, which is under statement. The US company has been responsible for commercializing the Financial Services Commission, has repeatedly held meetings to Samsung Bioepis’s anti-TNF biosimilar product candidates in Europe. determine if Samsung BioLogics has violated accounting standards “We are very pleased with the progress made to date at Samsung related to the reflection of Samsung Bioepis in its books. The FSC is Bioepis and believe exercising this option is an opportunity to create expected to unveil the results of its review in July. meaningful value for our shareholders,” said Biogen CEO Michel Vounat- In May, financial authorities reportedly concluded that Samsung sos. “This option allows us to increase our ownership share in a leading BioLogics violated accounting standards when it changed in 2015 its biosimilar company at what we believe are attractive terms. We look accounting related to Samsung Bioepis. Samsung BioLogics had been forward to building an important relationship with Samsung BioLogics.” reflecting Samsung Bioepis as a subsidiary in its consolidated financial The move wasn’t a complete surprise given that during its first statements, but changed it to affiliated company status in 2015. quarter 2018 earnings call, Biogen said it planned to exercise an op- As a result, Samsung BioLogics reflected the value of its stake in tion to increase its equity stake in the JV in the belief this would be an Samsung Bioepis to market value from book value, which resulted attractive value creation opportunity. in hefty one-off investment income. Samsung BioLogics said it had “Biogen’s option to increase its stake in the Samsung Bioepis joint made the change in accordance with IFRS requirements, and that venture was set to expire in mid-2018, so I’m not surprised Biogen this had been confirmed as adequate by external auditors. made a decision about the investment,” said Datamonitor Healthcare Local media have recently reported that the commission is now analyst Amanda Miklus. checking Samsung BioLogics’ books from 2012, when it first estab- But what is surprising is that only a month ago, Vounatsos made lished Samsung Bioepis as a joint venture with Biogen. comments at a Bernstein Strategic Decisions Conference indicating his company might not even continue with the joint venture, saying STRONGER BIOGEN REPRESENTATION “Biogen’s agenda is not to remain in a JV for the long run and would With the exercise of the option, Biogen will jointly run Samsung Bio- instead focus on its neuroscience assets,” the analyst noted. epis with Samsung BioLogics and have an equal number of seats However, the $700m investment Biogen is making to significantly on the JV’s board. Samsung BioLogics expects the transaction to be up its stake in Samsung Bioepis says quite the opposite. “I think this completed within three months. has been a successful collaboration for both Biogen and Samsung Since the joint venture was established, Biogen has been pro- BioLogics, with Bioepis launching several biosimilars and some in the viding its biologics development technology and know-how, pipeline. Now Biogen will be more heavily involved than before in helping to turn Samsung Bioepis into a leading biosimilars player decision-making and development I imagine,” Miklus said. globally, generating the highest number of products in its pipe- line referencing global top 10 drugs within just six years, Samsung IMPACT ON ACCOUNTING PROBE? BioLogics noted. Biogen’s stronger commitment to the joint venture is poised to help Samsung BioLogics CEO Tae Han Kim vowed to cooperate with Bio- further beef up Samsung Bioepis’s presence and leadership in the gen to further boost Samsung’s biosimilar business in global markets. global biosimilars market. However, in South Korea, the focus is more Samsung BioLogics announced in May that the company had on how the option could affect ongoing accounting issues at Sam- received approval from the US FDA for the manufacture of three sung BioLogics. Biogen’s call option exercise has been at the center of commercial biologic drug substances at its second plant within 26 an accounting controversy involving Samsung BioLogics – a leading months of the facility becoming GMP-ready in 2016. biopharma contract development and manufacturing organization Published online 2 July 2018 in South Korea – and the country’s financial authorities. From the editors of PharmAsia News.

8 | Scrip | 6 July 2018 © Informa UK Ltd 2018 GENERICS

Teva Retains Top Slot As Industry Akebia And Keryx To Merge Faces US Pushback In a transaction that “makes so MIKE WARD [email protected] much sense” according to CEO John Butler, two Boston-area biotechs has seen the Israeli giant cutting headcount focused on kidney disease – Butler’s and announce the closure of 10 production clinical-stage Akebia Therapeutics plants. Teva retained pole position after in- Inc. and Keryx Biopharmaceuticals corporating ’s Anda distribution busi- Inc. with struggling Auryxia already ness from the end of 2016. In the US, spe- on the market – will merge in a deal cifically, Teva has announced plans to drop they say will establish a leader in about 80% of its portfolio, moving them to their market segment. other suppliers, while looking to push price increases on its remaining 20%. In the first Complementary Franchise quarter, Teva’s North American generics The two companies announced the sales plummeted 23%. planned all-stock merger June 28, a Year on year, there was little change in transaction expected to close by the end the positions of the top ten companies, of 2018 that will leave Keryx sharehold- only Lupin Ltd. slipped out of the top ers owning 50.6% of the combined tier, down one place in 11th. With the top entity and Akebia shareholders 49.4%. seven companies retaining the same posi- Operating under the Akebia name, the espite increasing desire by payers to tions between 2016 and 2017, Valeant, up new firm will be led by Akebia’s existing curb drug costs by switching to less eight places on the 2016 ranking, was the CEO Butler, with Keryx getting the Dexpensive generics and biosimilars, top climber in at eighth place. Privately right to appoint the chairman of the most of the world’s leading companies in held Stada Arzneimittel AG, like seventh- board. The other eight seats on the the space struggled during fiscal 2017. Ac- ranked Fresenius Kabi AG, benefited from board will be split evenly between the cording to the latest rankings by Generics Bul- doing as much business in Europe as it two companies. letin, a sister publication of Scrip, companies does in the US and saw it rise one place to While the deal requires shareholder operating in the US generics and biosimilars ninth in the table. With its intention to make approval to be finalized, it has good market have struggled to maintain sales and more acquisitions in Europe and the MENA momentum. Both boards of direc- operating margins owing to an increase in region, as well as plans to invest $100m in tors gave unanimous approval, Akebia competitive products and consolidation biosimilars in the next three years, it is likely Chairman Muneer Satter agreed to among customers. the company might continue its rise in the contribute his 5.3% ownership stake in Indeed, the US headwinds are a major charts. Endo was the biggest faller in the top that company to the merger, and Bau- driver for Teva Pharmaceutical Industries 10 slipping three places to tenth. post Group LLC, which owns roughly Ltd.’s renewed focus on profitability which Published online 29 June 2018 21.4% of Keryx, has agreed to convert its outstanding convertible notes into 2017 Rankings For Generics Firms by Revenues ($m) Keryx common stock before closing and entered into a voting agreement to 2017 GENERICS/ 2016 GENERICS/ YOY back the merger. COMPANY 2017 RANK OTC/ BIOSIMILARS OTC/ BIOSIMILARS CHANGE In an interview, Butler said the com- REVENUES ($M) REVENUES ($M) (SM) pany’s strategy would revolve around optimizing the revenue potential of Teva 1 - No change 11,504 11,214 290 Auryxia (ferric citrate), a phosphate Mylan 2 - No change 11,060 10,967 93 binder approved by the US FDA in Sandoz 3 - No change 9,544 9,625 -81 2014 to treat hyperphosphatemia in Pfizer Essential chronic kidney disease (CKD) patients 4 - No change 6,204 6,337 -133 Health on dialysis. Last November, the drug 5 - No change 4,891 5,201 -310 added a second indication for treat- Sun 6 - No change 3,726 4,336 -610 ing iron-deficiency anemia in CKD patients not on dialysis. This drug and Fresenius Kabi 7 - No change 3,175 2,751 424 Akebia’s Phase III vadadustat would Valeant 8 - Up 8 places 2,686 1,544 1,142 create a complementary franchise, Stada 9 - Up 1 place 2,642 2,253 389 CEO Butler asserted. Endo 10 - Down 3 places 2,281 2,565 -284 [email protected], 28 June 2018

scrip.pharmaintelligence.informa.com 6 July 2018 | Scrip | 9 REGULATORY

PTI’s Remoxy: Negative FDA Panel Review May Be The End Of Abuse-Deterrent Opioid’s Road SUE SUTTER [email protected]

ain Therapeutics Inc. is standing on the verge of a regulatory an appeal through the agency’s dispute resolution process seems dead-end for Remoxy (oxycodone extended-release) following unlikely to provide much relief. Pa US FDA advisory committee’s negative review June 26, and The FDA is not likely to exercise its regulatory flexibility for a drug the company’s CEO warns that the “changing goalposts” might deter targeting a common condition (pain) and for which numerous other future development in the abuse-deterrent opioid space. long-acting opioids are available, including some that the agency al- The committee’s 14-3 vote against approval suggests the long- ready has determined satisfy its preapproval requirements for dem- acting opioid formulated with abuse-deterrent properties is headed onstrating abuse deterrence. for its fourth complete response letter in a 10-year regulatory saga. In addition, PTI would be hard-pressed to overcome the compari- Most members of the agency’s anesthetic/analgesic drug prod- sons made by FDA reviewers and advisory committee members of ucts and risk management/drug safety panels concluded that Pain Remoxy’s intravenous abuse potential to that of Opana, given the Therapeutics (PTI) had established Remoxy’s ability to deter intrana- latter’s safety issues and regulatory history. sal abuse. Endo removed Opana from the market after the FDA concluded However, they were troubled by the safety and public health im- the product’s reformulation led to a shift in the route of abuse from plications of the product’s intravenous abuse potential – concerns intranasal to intravenous, which in turn led to needle-sharing, trans- that the FDA reviewers and the panel equated to those that led to mission of bloodborn infections such as HIV and hepatitis C, and the withdrawal of Endo Pharmaceuticals Inc.’s Opana ER (oxymor- other serious adverse events. (Also see “Opana ER Withdrawal Adds phone extended-release). Weight To Endo’s Ongoing Revenue Decline” - Scrip, 7 Jul, 2017.) Panelists were also worried about the ability to partially defeat the In the FDA’s June 2017 announcement that it had asked Endo to Remoxy capsule’s extended-release properties by chewing it. withdraw the product, then-newly installed Commissioner Scott Gottlieb highlighted the regulatory action as part of the tough ap- proach the agency would take under his leadership to addressing ‘A sponsor would have to be the opioid crisis. Even if the FDA were to relent and approve Remoxy – a decision pretty naive, if not stupid, to that no doubt would unleash a fury of criticism from lawmakers and develop an abuse-deterrent opioid public health advocates – the drug likely would be saddled with neg- ative labeling on oral abuse-deterrence studies, further dimming its from scratch today because the commercial prospects in the eyes of any potential marketing partner.

goalposts keep changing’ 10-YEAR PURSUIT OF APPROVAL Remoxy has had a long, difficult regulatory journey in the US that has coincided with the growing opioid epidemic and an evolution in ‘IT’S OVER’ preapproval requirements as the FDA has focused increased atten- When asked by Scrip about prospects for Remoxy’s continued de- tion on the potential unintended consequences and adverse pub- velopment if PTI receives a complete response letter by the Aug. 7 lic health impacts from the approval of new opioid products, even user fee goal date, Chairman and CEO Remi Barbier said “it’s over,” those with properties aimed at deterring abuse. not because the company is giving up on the data, but “because the The drug has been the subject of three complete response let- goalposts keep changing.” ters since its initial submission in June 2008. The most recent letter In an interview, Barbier said the shifting preapproval regulatory in September 2016 cited the need for a human intranasal abuse li- requirements that PTI has experienced in trying to bring an abuse- ability study and additional laboratory-based in vitro manipulation deterrent opioid formulation to market will dissuade other sponsors and extraction studies. from entering this space. The current NDA seeks abuse-deterrent labeling by the intrave- “A sponsor would have to be pretty naive, if not stupid, to develop nous, intranasal and smoking routes of abuse. However, as other an abuse-deterrent opioid from scratch today because the goalposts sponsors in this space have learned, gaining such labeling is no guar- keep changing,” he said. antee for commercial success. (Also see “Abuse-Deterrent Opioids: He asserted the company did not receive the “fair and neutral” ad- Where Are They Now?” - Scrip, 20 Mar, 2018.) visory committee hearing to which it was entitled. The panel meet- A total of nine long-acting opioids and one immediate-release prod- ing “was all over” as soon as the FDA pronounced Remoxy and Opana uct have been approved with abuse-deterrent labeling as described in in the same sentence, Barbier said. the FDA’s April 2015 final guidance. This list includes two single-ingre- The CEO declined to comment on what recourse the company dient, extended-release oxycodone products: LP’s might seek if it receives another complete response letter. However, OxyContin and Collegium Pharmaceutical Inc.’s Xtampza ER.

10 | Scrip | 6 July 2018 © Informa UK Ltd 2018 REGULATORY

OxyContin holds the lion’s share of the abuse-deterrent formu- EXTRACTION DATA DEAL A FATAL BLOW lation (ADF) opioid market, accounting for nearly 88% (or 3.4m) What might have been the fatal blow for the Remoxy NDA were data of the 3.8m ADF prescriptions dispensed in 2017. Yet even Oxy- from in vitro extraction studies conducted by the FDA and presented Contin’s market-leading share represents only about 20% of the at the meeting. 17.5m total prescriptions for extended-release/long-acting opi- These study results were not included in the publicly released oids dispensed in 2017, according to outpatient retail pharmacy briefing document because the agency received them only a few data cited by the FDA in its briefing document for the Remoxy days before the meeting, the FDA told Scrip. “We did not share the advisory committee meeting. actual data with the company before the meeting, but did let them Several formulations approved with ADF labeling have never know that we would be presenting data from our lab that was differ- launched. On May 2, the new drug application (NDA) for one of ent than their data,” the agency said. those, Pfizer Inc.’s Troxyca ER (oxycodone/naltrexone extended- PTI’s in vitro studies suggested that oxycodone is more difficult to release), was withdrawn at the sponsor’s request. “We made the extract from Remoxy than from OxyContin and Xtampza ER, and that decision not to introduce another oxycodone as there are the product’s thick, sticky viscosity makes it difficult to draw up into a several abuse-deterrent oxycodone treatment options available to syringe for injection purposes. patients,” Pfizer told Scrip, though it said it remains committed to in- However, studies performed by the FDA showed that 72% of the novation in treating chronic pain. oxycodone content could be extracted from Remoxy using a partic- Pfizer, which markets an ADF formulation in Embeda (morphine/ ular method, solvent, volume and time, and a “slightly more involved naltrexone extended-release), once owned the rights to Remoxy process” involving pretreatment resulted in extraction of up to 83% through the big pharma’s acquisition of Inc. of oxycodone, Wiltrout said. However, it returned those rights to Pain Therapeutics in 2014. “The take-home message is that fairly basic manipulation and Remoxy is PTI’s lead pipeline product, and the negative advisory extraction methods generated a high yield of oxycodone suit- committee review had an outsized impact on the company’s valuation. able for injection,” Wiltrout said. “Moreover, these manipulation Trading in the company’s stock was halted on the day of the advisory and extraction methods are presumed to be readily available in committee meeting, but the stock lost 71% of its value the following the community.” day, closing at $2.44 on June 27, down from the June 25 close of $8.53. “Implications of the FDA lab findings are clear,” Wiltrout said. “Oxy- Remoxy incorporates Durect Corp.’s Oradur technology, and the codone suitable for I.V. use can be extracted from Remoxy ER. The company would be owed milestone payments upon approval. Du- amount of extracted oxycodone and the extraction volume may lead rect stock closed at $1.70 on June 27, down 11% from its June 25 close. to sharing among I.V. drug users. Given what happened with Opana ER, other important public health consequences are to be expected.” THUMBS UP FOR NASAL DETERRENCE, BUT Wiltrout also said that PTI had not sufficiently studied the safety of CONCERNS ABOUT CHEWING Remoxy’s excipients when the product is manipulated for purposes of At the advisory committee meeting, Division of Anesthesia, Anal- gesia and Addiction Products (DAAAP) Medical Officer Lisa Wiltrout extracting oxycodone for intravenous use. She noted that Opana I.V. said that PTI’s intranasal human abuse liability study data provided drug users experienced thrombotic microangiopathy, which investiga- in the most recent submission met the current standards for abuse- tions showed was due to injection of an excipient in Endo’s formulation. deterrent labeling. The regulator’s drawing of parallels between Remoxy and Opana Pharmacokinetic results demonstrated that intranasal administra- resonated for several advisory committee members. tion of Remoxy may result in significantly lower plasma oxycodone “I do have concerns this this will be manipulated and is able concentrations compared to intranasal administration of crushed to be extracted, and you could see similar HIV and HCV transmis- immediate-release oxycodone. Remoxy was associated with statis- sions, because we know that if it can be extracted people are go- tically significantly lower scores than immediate-release oxycodone ing to do that,” said Jon Zibbell, senior public health scientist at on visual analog scales that measured drug effect liking, drug high, RTI International. desire to take the drug again, and overall drug liking, and it was The panel’s consumer representative, Suzanne Robotti, executive shown to be more difficult to administer intranasally than immedi- director of DES Action USA, noted she sat on the March 2017 advi- ate-release oxycodone powder, the FDA said. sory committee review of the postmarketing experience with Opa- However, Wiltrout appeared to foreclose the path to a smoking na. “That’s a terrible unforeseen outcome” that should be prevented abuse-deterrence claim. “Based on our analysis of available epide- from happening again, she said. miological and in vitro data, we do not consider smoking a relevant route of abuse for oxycodone,” she said. FDA STATEMENT ‘BORDERS ON SLANDEROUS’ In the current application, PTI did not request deterrence labeling For PTI, the FDA’s comparison of Remoxy to Opana was both surpris- language by the oral route of abuse, even though the formulation – ing and unjustified. “We had not seen their extraction data,” Barbier consisting of a sticky gel – is intended to deter such abuse. said of the FDA’s studies. “Remoxy is very difficult to extract.” He noted Some panelists suggested that if approved, the FDA should in- also that the FDA showed no data on extraction rates of comparator clude in Remoxy labeling negative results of studies aimed at dem- drugs using the same methods. onstrating the formulation’s oral abuse-deterrent effects. In a human Opana “was a dangerous drug,” Barbier told Scrip. “For the FDA to oral abuse liability study, chewing Remoxy resulted in much higher compare Remoxy and Opana in the same breath in the same sentence peak serum concentrations, and greater drug liking effects, than during a public hearing, in my opinion, borders on slanderous.” swallowing the drug intact as intended, the agency said. Published online 28 June 2018 scrip.pharmaintelligence.informa.com 6 July 2018 | Scrip | 11 APPROVALS

Array Raring To Go With First Approval: Mektovi/Braftovi EMILY HAYES [email protected]

he US FDA approved Array Bio- Array is hoping to gain share by offering states that overall survival data were not pharma Inc.’s MEK inhibitor Mek- eligible commercial patients a zero copay mature at the time of analysis. T tovi (binimetinib) and BRAF inhibitor deal for the drug and supporting patients The company noted that in the study me- Braftovi (encorafenib) for combination treat- and physicians, to make getting therapy as dian overall survival was 33.6 months for the ment of metastatic melanoma on June 27. easy as possible. combination versus 16.9 months for those This marks Array Biopharma’s transition into taking Zelboraf monotherapy. a commercial enterprise, and the company HOW TO COMPETE Array reported that the combination was has been preparing to launch immediately. Array likely will find that the melanoma generally well tolerated in COLUMBUS, with Prior to approval, it had already put 60 market is a bit daunting, as the other tar- including rash, pyrexia and se- customer facing team members in place, geted BRAF/MEK inhibitors have a long rous retinopathy. Labeling notes that adverse including representatives working with lead. Roche’s Zelboraf was approved in 2011 events caused dose interruptions in 30% of prescribers and payers and medical science followed by Cotellic in 2015, while Novartis’ patients on the combo, dose reductions in liaisons working with thought leaders. This combination was approved in 2013. 14% and permanent discontinuation in 5%. is about the same size as a large pharma Novartis has reported strong sales for its This is the first oral combination in the would have in place, CEO Ron Squarer told combo, up by 29% to $873m in 2017. indication to offer median overall survival Scrip in an interview. Roche didn’t break out sales of Zelboraf greater than 30 months, Squarer said. “We are matching what is common,” the and Cotellic in its 2017 report. Although exec said. Zelboraf was the first approved BRAF inhibi- HEAVY COMPETITION The combo, cleared just before the June tor, Novartis was first to market with a BRAF/ Array says it is not concerned about the 30 user fee date, is indicated to treat patients MEK combination and adding a MEK inhibi- entry of Novartis’ BRAF/MEK combo into with unresectable or metastatic melanoma tor substantially improves the BRAF agents’ adjuvant melanoma. Many patients are not with either a BRAFV600E or BRAFV600K mu- adverse event profile. diagnosed until they are metastatic and tation, as determined by an FDA-approved retreatment with BRAF/MEK combination diagnostic test. Braftovi is not indicated for TAKING COMPETITION IN STRIDE would still be possible. Furthermore, Squar- wild-type BRAF melanoma. Array said Mek- Array acknowledges the competition but er believes that a PD-1 inhibitor is going to tovi/Braftovi is now available through select believes it has a few things on its side aside be preferred in the adjuvant setting over US specialty . from the patient assistance plan, including a BRAF/MEK combination due to a better Array negotiated rights to both drugs in the data supporting the filing. Backing the safety profile. 2015 from Novartis AG, which at the time NDA was the Phase III COLUMBUS study in “That is our assumption and that is what was gaining the BRAF and MEK inhibitors Ta- 577 patients with BRAF-mutant melanoma. we have consistently what we have heard finlar (dabrafenib) and Mekinist (trametinib), The first part of the trial was designed to from thought leaders,” Squarer said. respectively, from GlaxoSmithKline PLC. evaluate what binimetinib was contributing: There are still only two modalities in mel- The combination is partnered with Pierre 577 patients were randomized to encorafenib anoma – IO and BRAF/MEK – and the vast Fabre Group in Europe and emerging mar- at 450 mg with binimetinib at 45 mg, en- majority of patients will get both, he said. kets. Filings in Europe, Australia and Switzer- corafenib monotherapy (300 mg) or vemu- Meanwhile, the company is developing land are under review. rafenib at 960 mg. In Part 2, the company the BRAF/MEK combination in combination Array also is in talks with the FDA regard- compared progression-free survival in pa- with checkpoint inhibitors in the larger indi- ing accelerated approval of the combina- tients treated with binimetinib at 45 mg twice cation of colorectal cancer. tion – for use with Lilly’s anti-EGFR Erbitux daily with encorafenib 300 mg daily to an arm The Phase III BEACON study is evaluating () – in a subset of colorectal can- treated with encorafenib at 300 mg daily. binimetinib/encorafenib and Eli Lilly & Co.’s cer based on interim PFS and response rate The study met its primary endpoint, with Erbitux (erlotinib) in BRAF mutant metastatic data from the Phase III BEACON study, which encorafenib/binimetinib demonstrating su- CRC (BEACON CRC). Data for 30 patients in is due to report at the end of the year. Jef- perior PFS over vemurafenib (14.9 months a lead-in part of BEACON were presented at feries analyst Eun Yang has estimated a sales vs. 7.3 months, p<0.0001). But a second- the European Society of Medical Oncology opportunity of $1bn, as colorectal cancer is ary endpoint evaluating the encorafenib/ gastrointestinal cancer meeting in Barcelona a much larger patient population. binimetinib combination compared to en- on June 23. Median progresion-free survival Between Novartis’ Tafinlar/Mekinist duo corafenib alone was missed, as the combi- was eight months for the triplet and the and Roche’s Zelboraf (vemurafenib) and Co- nation was numerically but not statistically confirmed objective response rate was 48% tellic (cobimetinib), breaking into the BRAK/ superior to encorafenib alone (median PFS overall and 62% in those who had only one MEK segment of the metastatic melanoma of 14.9 month versus 9.6 months (p=0.051)), prior line of therapy, the company reported. marker will be tough, especially as the mela- raising questions about what binimetinib Median overall survival had not yet been noma market is now dominated by immu- was contributing. Labeling does not report reached. no-oncology. the encorafenib alone comparison, and Published online 28 June 2018

12 | Scrip | 6 July 2018 © Informa UK Ltd 2018 APPROVALS

Dermira Wins First FDA Approval, For Qbrexza MANDY JACKSON [email protected]

ermira Inc. claimed an important victory when it won US a May 24 investor day presentation that “we expect it will be about FDA approval for Qbrexza (glycopyrronium) – a topical an- five years to six years for us to achieve peak sales with glycopyrro- Dticholinergic delivered by a cloth wipe – on June 29 for the nium tosylate. The market opportunity is significant, but the invest- treatment of primary axillary hyperhidrosis (excessive underarm ment required to build awareness and activate the patients is not sweating) in patients aged 9 and older. trivial, so we do expect a slow initial build, though a significant op- The agency’s decision marks the company’s first-ever drug ap- portunity in the long-term.” proval and it provided the Menlo Park, Calif., company with a needed The company already has made significant investments in direct- win after highly anticipated Phase III clinical trials for its now-discon- to-consumer advertising to create patient awareness of this new tinued drug candidate DRM01 failed in March. Dermira intends to treatment option, since only about 15% of individuals with excessive make once-daily Qbrexza available for prescription in October with underarm sweating are seeking treatment, even though it’s estimat- high hopes for growing an underserved market and winning reim- ed that about 50% have talked to their doctor about their condition. bursement for the novel product. Dermira brought in a patient and doctors to speak with investors Hyperhidrosis is a 15m patient market in the US, including 10m during its presentation in May to illustrate the severity of hyperhidro- people with axillary, or underarm, hyperhidrosis. Aluminum salts, sis and the need for new treatment options. i.e. the prescription antiperspirant Drysol, and Allergan PLC’s Botox Patient Timothy Lawrence, for instance, talked about changing (onabotulinumtoxinA) are the two main prescription therapies, but clothes multiple times per day and sweating through three layers Dermira estimates that only 800,000 patients are receiving those or of clothing – an undershirt, dress shirt and suit coat – during the other treatments for the condition. course of a single business meeting. Yet, he said the psychological Qbrexza inhibits the interaction between acetylcholine and the and emotional impacts of excessive sweating were more severe than cholinergic receptors that activate sweat glands. Dermira may also the physical symptoms of hyperhidrosis. purse development of the drug in palmar hyperhidrosis or excessive Dermira Chief Commercial Officer Lori Lyons-Williams worked on sweating of the hands. the hyperhidrosis launch for Botox and said during the company’s in- Patients have been seeking new therapies for hyperhidrosis and vestor day presentation that she drew three lessons from that experi- not just for excessive sweating on the hands and underarms. Avail- ence that apply to her thinking about Qbrexza: 1) the disease has a able therapies can be expensive, since many payers won’t cover the meaningful impact on patients’ lives, 2) there were not – and 15 years costs of Botox or microwave thermolysis, and those treatments can later, still are not – great treatments options for this disease, and 3) a be burdensome; Botox requires up to 100 injections per treatment. treatment that does work is life-changing for these patients. Dermira CEO Tom Wiggans said in the company’s statement about Lyons-Williams noted that the Dermira product has a good chance the approval that “our goal was to develop an approach that went of becoming a significant product, because “the fact that it’s novel beyond masking a person’s excessive underarm sweating and instead and topically delivered and can cut sweat in half … I think is really focused on treating the condition in a clinically meaningful way.” something that, at least according to our testing with patients, is The FDA considered the company’s two successful Phase III clinical something that’s going to resonate quite well.” trials, known as ATMOS-1 and ATMOS-2, in deciding whether to ap- prove Qbrexza. The primary endpoints in both studies were the abso- GOOD PRESCRIBER, PAYER RESPONSE ANTICIPATED lute change from baseline in sweat production and the proportion of She noted low patient and prescriber satisfaction with available patients with at least a four-point improvement from baseline in sweat- therapies, and said 50% of doctors surveyed by the company would ing severity as measured by the Axillary Sweating Daily Diary (ASDD), prescribe Qbrexza as a first-line therapy after over-the-counter anti- Dermira’s proprietary patient-reported outcome (PRO) instrument. perspirants. The other 50% said they’d try prescription-strength alu- Dry mouth, dry skin, dry eyes, dry throat, dry nose, urinary hesi- minum chloride-based antiperspirants first. tancy and constipation were among the drug’s most common side Fortunately, Lyons-Williams said, payers are interested in novel effects, which wasn’t surprising based on the known side effects for therapies for hyperhidrosis and have indicated a willingness to pay systemic anticholinergic agents. Labeling recommends that Qbrexza for the product. They already cover Botox and have said that Dermi- is not prescribed to patients taking other anticholinergic drugs. ra’s data in patients as young as nine years old is differentiating. That’s good news for Dermira, which has no imminent competition in this MODEST SALES EXPECTED INITIALLY space, since there are no late-stage drugs, devices or procedures in Since the drug isn’t launching until October, Evercore ISI analyst development for this disease. Umer Raffat estimated in a June 29 note that Qbrexza will gen- Compounded versions of topical creams or ointments containing erate $30m in 2019 sales, rising to $68m in 2020 and $118m in glycopyrronium sometimes are prescribed, but those products have 2021. Raffat forecast $200m in peak annual sales. That would make not been consistent, according to dermatologist Dee Anna Glaser, Dermira’s product the market leader in hyperhidrosis, since annual professor and interim Chair of Dermatology at Saint Louis University Botox sales in this indication have plateaued at about $70m as Al- School of Medicine, during Dermira’s investor presentation. lergan has de-emphasized its marketing efforts in hyperhidrosis. “I think the issue is that each time I write a prescription, I get some- Dermira Chief Financial Officer Andrew Guggenhime said during thing different.” Published online 2 July 2018

scrip.pharmaintelligence.informa.com 6 July 2018 | Scrip | 13 APPROVALS

GW’s Epidiolex Approval Encouraging For Pharma- Grade Cannabinoid Pipeline EMILY HAYES [email protected]

S FDA approval of GW Pharmaceuticals PLC’ marijuana approximately $6,500. (Also see “Eisai’s Banzel gets US approval and plant-derived product Epidiolex in rare epilepsy disorders sets complete response letter for epilepsy” - Scrip, 18 Nov, 2008.) Ua regulatory precedent and is encouraging for the large pipe- The market factors will allow GW to maximize the commercial op- line of cannabinoid candidates in development for various disorders. portunity, Yip told Scrip, and noted that Datamonitor is projecting The agency cleared Epidiolex (cannabidiol, or CBD) oral solu- sales of $822m in 2025. tion on June 25 for the treatment of Lennox-Gastaut syndrome Although there is nothing else approved for Dravet Syndrome, (LGS) and Dravet syndrome (DS), noting that this is “the first FDA- Epidiolex does have a competitor on the near horizon. Zogenix Inc.’s approved drug that contains a purified drug substance derived oral serotonin reuptake inhibitor ZX008 (low-dose fenfluramine) has from marijuana.” In addition to setting a precedent in that the drug shown impressive effects in reducing the number of monthly sei- is the first plant-derived cannabinoid to win approval, the decision zures for patients with this condition. (Also see “Stellar Zogenix Phase is also ground-breaking because Epidiolex is the first approved for III Epilepsy Data Lift ZX008’s Competitive Position” - Scrip, 29 Sep, 2017.) Dravet syndrome. A filing is expected in the second half. Importantly, Epidiolex does not include tetrahydrocannabinol (THC), which is associated with the psychoactive effects of mari- A TURNING POINT FOR CANNABINOIDS juana. Synthetic versions of THC that have been approved by FDA The development space for cannabinoids has been challenging. include AbbVie Inc.’s Marinol (dronabinol) and Mylan NV’s Cesamet Initially, they were developed for obesity. Sanofi withdrew an NDA (nabilone). GW Pharma markets Sativex (nabiximols) buccal spray, for Zimulti (rimonabant) in 2007 and took the drug off the market in which includes CBD and THC and is derived from cannabis plants, 2008 in Europe due to the risk of psychiatric side effects. Since then, outside the US for spasticity associated with multiple sclerosis. the field has shifted to development in what is considered more seri- FDA Commissioner Scott Gottlieb stressed in a statement about ous conditions, like severe forms of epilepsy. the Epidiolex news that this is not a broad approval for marijuana. GW sees its plant-based approach as offering advantages over oth- “This is the approval of one specific CBD for a specific er drugs in the pipeline, which largely consists of synthetic candidates. use. And it was based on well-controlled clinical trials evaluating the The company aims to provide a standardized, entirely pure formula- use of this compound in the treatment of a specific condition,” Got- tion, with no other parts of marijuana aside from CBD, or impurities. tlieb said. Stephen Schultz, GW’s vice president of investor relations, said in Epidiolex currently has Schedule I status with the US Drug Enforce- an interview that the company has refined the science over 20 years ment Agency, which would severely limit access, but the company of working in the space and is able to grow plants with a specific believes that it will likely be rescheduled to a very unrestricted level cannabinoid profile. Generation after generation, the plants are ex- – Schedule IV or V. actly the same, which is what patients and physicians expect from The rescheduling of Epidiolex, ensuring wide access, would be an a medicine, he said. The cannabinoid pipeline includes at least 27 encouraging development for GW in terms of its own further devel- drugs in clinical development, according to Informa’s Pharma Intel- opment and the cannabinoid pipeline generally, noted Datamonitor ligence Biomedtracker database. Healthcare analyst Stephanie Yip. In addition to Epidiolex in tuberculosis sclerosis complex, the late- GW Pharma also has Epidiolex in Phase III for tuberous sclerosis stage compounds include Insys Therapeutics Inc.’s synthetic for- complex and Phase II/III for infantile spasms. mulation of cannabidiol, which is in Phase III for seizure disorders and infantile spasms. Other drugs are in clinical development for a range COMMERCIAL TEAM READY, PRICING STILL IN of conditions, including acute pain, graft-versus-host disease, sclero- THE WORKS derma, schizophrenia and substance use disorder. The company already has a commercial team in place to market the There also are 49 pipeline products in preclinical development drug for its initial indications in the US, with 70 reps geared up to that target the cannabinoid type 1 receptor and these are being reach 4,000 to 5,000 specialist epilepsy prescribers. The patient popu- tested in 47 different indications spanning neurology, psychiatry, on- lations are small – 8,000 people have Dravet Syndrome and 35,000 cology, metabolic diseases, respiratory disease, endocrine and infec- have Lennox-Gastaut syndrome. tious disease, according to Biomedtracker. GW has not set a price yet for Epidiolex, but Yip notes that there “This reflects the excitement surrounding the potential for medical is no other FDA-approved option for Dravet syndrome so there is marijuana as companies are willing to invest in testing these prod- high unmet need in a niche space and this is a first-in-class drug, so ucts for a wide array of diseases, as they perceive the commercial it could be priced at a premium. Yip points out that Eisai Co. Ltd.’s opportunity for this new ,” Datamonitor’s Yip said. Banzel (rufinamide), which is FDA-approved for Lennox-Gastaut Syn- Over time as clinical data roll in, the field may become more tar- drome, commands an annual price of about $20,000, whereas the geted at particular conditions. average annual price across other key branded is Published online 29 June 2018

14 | Scrip | 6 July 2018 © Informa UK Ltd 2018 CHMP MEETING

Cablivi CHMP Backing Helps Validate Sanofi’s €3.9bn Ablynx Purchase STEN STOVALL [email protected]

he logic behind Sanofi’s purchase Cablivi be prescribed and supervised by of Ablynx NV this year has had an physicians experienced in the treatment T important validation from the Eu- of management of patients with throm- ropean Medicines Agency’s Committee for botic microangiopathies. Medicinal Products for Human Use (CHMP) Detailed recommendations for the use of which has recommended approval of Cablivi the product will be described in the sum- () in Europe for treating adults ‘Cablivi significantly mary of product characteristics, which will experiencing an episode of acquired throm- be published in the European public assess- botic thrombocytopenic purpura (aTTP), a curtails costly ment report (EPAR) and made available in all rare blood-clotting disorder. plasma exchange, official European Union languages after the Cablivi was developed by Ablynx, now a marketing authorization has been granted Sanofi company. It is a first-in-class anti-von a risky procedure, by the European Commission. Willebrand factor (vWF) Nanobody for the Analysts at Jefferies in a note said Ca- treatment of aTTP. reduces the risk blivi “significantly curtails costly plasma ex- Marketing approval by the European of exacerbations, change, a risky procedure, reduces the risk Commission for Cablivi is now expected of exacerbations, and protects organ dam- around the end of August or early Septem- and protects organ age, providing a window for physicians to ber. It has orphan drug status in both the EU resolve the underlying disease acquired TTP.” and US. Sanofi expects to launch the drug damage’ in the US next year as a treatment for aTTP. ABLYNX REWARDED LOYAL Analysts at Berenberg said Cablivi “for ac- SHAREHOLDERS quired TTP, has proven efficacy and should Ablynx’s investors have already been hugely be widely adopted. Depending on price, rewarded, although they needed patience this should easily become a €500m-plus after its initial IPO on Euronext Brussels in product. We forecast sales approaching 2007 as Cablivi was developed. €600m by 2025.” But in September 2017, positive Phase Sanofi’s internal projections are more III results for aTTP catalyzed a rerating for optimistic. A presentation made by Ablynx Ablynx stock from around €12 per share, at JP Morgan in January estimated annual and in January 2018, Novo Nordisk AS bid market potential for Cablivi being €1.2bn, €28/share (plus €0.50 in CVRs) for the com- aided by patent protection up to 2035. pany, which the board rejected. (Also see Acquired thrombotic thrombocytopenic “Novo Outbid As Sanofi Agrees €3.9bn Ablynx purpura is a life-threatening disorder with Acquisition” - Scrip, 29 Jan, 2018.) Just weeks a sudden onset caused by impaired activ- later, Sanofi announced that it would acquire ity of the ADAMTS13 enzyme, resulting in a Ablynx at €45/share, a staggering 112% pre- severe low platelet count (thrombocytope- mium to its undisturbed price. Sanofi on nia) and micro-clot formation in small blood June 19 completed its acquisition of Ablynx vessels throughout the body that cause for a total consideration of around €3.9bn. thrombotic complications and widespread reduced the number of patients experienc- The acquired Belgium-based division of organ damage. ing major thromboembolic events, as com- Sanofi develops Nanobodies, proprietary Cablivi’s EU marketing authorization ap- pared to placebo. therapeutic proteins based on single-do- plication includes data from the Phase II Cablivi will be made available to patients main antibody fragments, which combine TITAN study in patients with aTTP which by Sanofi Genzyme, Sanofi’s specialty care conventional antibody drugs with some demonstrated a statistically significant and business, and will be part of the unit’s new of the features of small-molecule drugs. clinically meaningful benefit of Cablivi treat- rare blood disorders franchise that will launch Ablynx has more than 45 proprietary and ment in reducing the time to platelet count in 2019 and which will also include Biovera- partnered programs in development in normalization and reducing recurrences tiv’s treatments for hemophilia A and B. various therapeutic areas including inflam- while on drug treatment. Results of post- The CHMP said Cablivi will be avail- mation, haematology, immuno-oncology, hoc analyses of the Phase II TITAN study fur- able as a 10 mg powder and solvent for oncology and respiratory disease. ther demonstrated that Cablivi dramatically solution for injection. It is proposed that Published online 30 June 2018 scrip.pharmaintelligence.informa.com 6 July 2018 | Scrip | 15 RESEARCH & DEVELOPMENT

AbbVie To Take Flight From Galapagos As PELICAN Flounders? ALEX SHIMMINGS [email protected]

he first Phase II data for Galapagos The two firms have long been playing CF patients which it hopes will reveal a po- NV’s novel C2 corrector for cystic fi- catch-up to Vertex in this field. They signed tential synergistic effect of GLPG2737 on top T brosis, GLPG2737, may have hit the a potential $405m deal back in 2013 with of its own dual combination compounds. primary endpoint in the PELICAN study but the explicit aim of developing a superior This triple combination comprises potentia- its efficacy can’t hold a candle to rival Ver- treatment to Vertex’s CFTR potentiator iva- tor GLPG2451, C1 corrector GLPG2222, and tex Pharmaceuticals Inc.’s investigational caftor (Kalydeco), the first disease modifying C2 corrector GLPG2737, and initial data for products, raising the likelihood of partner therapy for CF. the lower doses being tested are expected AbbVie taking off. in the third quarter. The trial tested GLPG273, a corrector ‘Clearly this is another Credit Suisse analysts said the PELICAN molecule that helps the cystic fibrosis trans- data raised significant concerns about membrane conductance regulator (CFTR) Galapagos/AbbVie FALCON and the competitiveness of the protein to move to the cell surface, added partnership that is now entire CF franchise. to Orkambi(lumacaftor + ivacaftor), Vertex’s Moreover, a second collaboration with combination of a corrector and a potentia- frayed, and we believe it will AbbVie now lies under a cloud following its tor (ivacaftor, a molecule that helps chloride likely need to be terminated previous decision to drop the JAK inhibitor flow through the CFTR protein channel), but filgotinib in 2015 (it was soon picked up by the top-line results were mixed. in the near future’ Inc.). “Clearly this is an- Compared with placebo, the product other Galapagos/AbbVie partnership that significantly reduced sweat chloride from is now frayed, and we believe it will likely baseline by a mean 19.6 mmol/L (p=0.02) need to be terminated in the near future,” in 22 adult CF patients who were homozy- But they have since found themselves left Credit Suisse analysts said in a June 29 re- gous for the Class II F508del mutation and well in Vertex’s wake as it sped ahead with search note. on stable treatment with Orkambi. development of a range of new therapies. The analysts do note a glimmer of hope But there was only a positive trend in Vertex launched Orkambi in 2015, for the for the CF franchise based on the fact that ppFEV1 change, a secondary endpoint. treatment of CF in patients aged 12 years Galapagos has another triple combination The mean absolute change from baseline and older with two copies of the F508del (‘3067 + 2222 + 3221) that does not involve in ppFEV1 for the GLPG2737 treatment arm mutation. And earlier this year in the US, 2737. But then again, they added, “Without versus placebo through day 28 was 3.4% Vertex launched its third disease-modifying the CF franchise and AbbVie collaboration (p=0.08). Further details are still to be pre- therapy Symdeko, containing its next-gen- one could argue Galapagos is now a cleaner sented. eration CFTR corrector-potentiator combi- story for a potential takeout, especially for This 3.4% increase in ppFEV1 falls short nation, tezacaftor/ivacaftor, for people aged a company like Gilead that is already part- of the +5% threshold that is generally 12 and older who have two copies of the nered with Galapagos on filgotinib.” deemed the minimum needed for an ef- F508del mutation in the CFTR gene or who Analysts at Jefferies said AbbVie’s decision fective drug. It falls still further short of have at least one mutation that is respon- on the second triple combination came “as the 7.8% to 13.8% improvements seen for sive to tezacaftor/ivacaftor. a surprise, as this has been viewed as the Vertex’s own candidates (VX-659 and VX- Vertex is now pressing ahead with po- preferred triple since potentiator ‘2451 has a long metabolite half-life.” But they feel that 445) when added to its newer dual com- tential triple therapy combinations of its the news could help reset expectation on bination of tezacaftor/izacaftor (Symdeko) investigational CFTR corrector therapies the program that they feel may have been in similarly homozygous patients or the added to the tezacaftor/ivacaftor backbone. overdone. “We highlight the ‘1972 osteoar- difficult-to-treat F508del/minimal func- It recently chose two – VX-659 and VX-445 thritis (OA) and ‘1690 idiopathic pulmonary tion mutations. Corresponding changes – to take into Phase III trials. Triple therapies fibrosis programmes, which we believe are in sweat chloride for these drugs were are expected to bring treatment options to under-recognized despite better econom- -31mmol/L to -54.3mmol/L. more patients expanding what is predicted ics for Galapagos.” On the back of the data, AbbVie has de- to become a multibillion-dollar market. Published online 30 June 2018 cided not to proceed with a second triple combination consisting of the same cor- SALVAGE OPERATION Click here to read “AbbVie rector components combined with poten- In the meantime, Galapagos is left to salvage Calico Extend Their tiator GLPG3067 and Galapagos said it was what it can from its CF program. The compa- Collaboration On Aging”: reviewing the future of the CF collaboration ny has already begun dosing in the FALCON https://bit.ly/2lTXCMG with AbbVie. trial, looking at higher doses of GLPG2737 in

16 | Scrip | 6 July 2018 © Informa UK Ltd 2018 HEADLINE NEWS

Scrip Awards 2018

Book your table The 14th Annual Scrip Awards

2018 www.scripawards.com

28 November 2018 | The Hilton on Park Lane, London, UK

Entry and General Enquiries: Natalie Cornwell Tel: +44 (0) 7827 993 776 | Email: [email protected]

Sponsorship and Table Booking Enquiries: Christopher Keeling Tel: +44 (0) 20 3377 3183 | Email: [email protected]

Sponsored by Headline Sponsor

scrip.pharmaintelligence.informa.com 6 July 2018 | Scrip | 17

JN1238 Scrip Awards 2018 Book your Table Advert A4.indd 1 2018/07/02 18:37 RESEARCH & DEVELOPMENT

Novo Nordisk Touts First-Line Potential For Oral Semaglutide EMILY HAYES [email protected]

ovo Nordisk AS believes the dataset for its oral GLP-1 recep- the magnitude of the A1C results for both methods in the PIONEER tor agonist semaglutide support the investigational drug’s data reported so far, except for PIONEER 1, due to the placebo com- Npotential to one day unseat the generic mainstay parator. Looking at weight loss, there was generally a lesser effect in as a first-line pill for type 2 diabetes. PIONEER 1 and other trials for the ITT method vs. the on-treatment The American Diabetes Association (ADA) annual meeting, held analysis, Biomedtracker said. June 22-26 in Orlando, was like a coming out party for Novo’s oral In PIONEER 1, the placebo group did surprisingly well in terms of semaglutide. weight loss, but those on oral semaglutide continued to lose weight, Just days before the meeting, the company announced topline which is a unique feature of the molecule, Thomsen said during the results from the pivotal PIONEER 4 study showing that the drug out- ADA investor briefing. performed its successful once-daily GLP-1 injectable Victoza (liraglu- “These data really just tell us the story that we have an extremely tide) – a major coup. efficacious first-line agent,” Thomsen said. During a June 24 investor briefing, the company said that it thinks As to whether the drug could displace metformin for first-line oral semaglutide is well-placed to become a first-line oral GLP-1 ago- use, Thomsen noted that there has been debate on this topic and nist based on data from the first pivotal trial PIONEER 1, which was pointed out the limitations of metformin. Metformin cannot be detailed at the ADA meeting, and celebrated the early commercial used in renally impaired patients, for example, and there is a need success of the subcutaneous weekly injectable formulation Ozempic. for more substantiation of cardiovascular/mortality benefits in the Ozempic (semaglutide) was approved by the US FDA at the end company’s view. of 2017, having bested Eli Lilly & Co.’s once-weekly GLP-1 Trulicity Oral semaglutide clearly would cost more than generic metformin. () in terms of blood sugar lowering and weight loss in the However, the exec said he can work with the “price versus the vol- SUSTAIN-7 study. ume elements of the franchise,” and so it is “not unrealistic in the fu- Mads Krogsgaard Thomsen, executive VP and chief science officer ture oral semaglutide could be considered a highly realistic first-line at Novo Nordisk, told the investor briefing there is much for the com- treatment option in big parts of the world.” That is why the company pany to be excited about, but he is most excited about the PIONEER did studies from cradle to grave with PIONEER 1 to 10, he explained. data rolling in for oral semaglutide. Stephen Gough, chief medical officer, acknowledged that “there’s Novo notes that its PIONEER program covers the entire treatment a massive comfort factor with metformin because it’s been around a cascade, with studies in a variety of settings, including as monothera- long time,” but added that the company has to think ahead about the py and as an add-on to and in patients with renal impairment advantages of the newer drugs that could exceed metformin. (see graphic). All of the studies will read out this year, with the final “It’s not going to change overnight, but I think there will be a move release in the fourth quarter. to displace [metformin]. And I think at some point, it will happen. I Thomsen noted that PIONEER 1, which tested oral semaglutide as hope it will happen,” Gough said. a monotherapy in treatment-naïve patients, supports this “cradle to However, current ADA guidelines indicate that metformin mono- grave” approach. therapy is the first treatment for type 2 diabetes unless there are con- Novo had reported positive top-line data from PIONEER 1 in Febru- traindications, and that metformin is “effective, safe and inexpensive ary, but the way it released the data left a lot of questions. and may reduce risk of cardiovascular events and death.” For approval and labeling purposes, the FDA generally prefers clin- ical trial data from an intent-to-treat (ITT) population of all comers in PIONEER 4 MAKES A SPLASH a trial, not the number who adhered to treatment. But Novo Nordisk A key goal for Novo Nordisk has been to develop a tablet with the reported only minimal data for the intent-to-treat population while same efficacy as its injectable GLP-1 Victoza, to expand the class’ offering more details for those who adhered to therapy and did not reach into a broader patient population. Primary care doctors are re- need rescue medication. The on-treatment population data is what luctant to prescribe injectables, Ted Hobbs, Novo’s North American clinicians and payers traditionally used to compare products. chief medical officer for diabetes, explained to Scrip in an interview. Oral semaglutide met the statistical definition for blood sugar low- That goal was achieved in the PIONEER 4 study, which compared ering (hemoglobin A1c, or HbA1c) at three doses using the FDA’s oral semaglutide to Victoza. Results were announced in a topline re- preferred ITT method, and met the weight loss goal at the highest lease on June 20, along with positive data from PIONEER 7, which dose tested (14 mg). And with the on-treatment approach, all three tested oral semaglutide against Merck & Co. Inc.’s DPP-4 inhibitor doses achieved significant blood sugar lowering vs. placebo, but Januvia (sitagliptin). only patients on the highest dose achieved significant weight loss. The results from PIONEER 4 looked strong in both the intent-to- At the ADA meeting, the company reported the detailed results for treat and the on-treatment analyses. both methods in the 703-patient study. Biomedtracker analysts note “This data is important, as it positions oral [semaglutide] as at least that in general for the high dose, there was not much difference in as good as the market leading injectable GLP-1. The result should

18 | Scrip | 6 July 2018 © Informa UK Ltd 2018 RESEARCH & DEVELOPMENT

PIONEER 1 Analysis: Oral Semaglutide vs. Placebo ANALYSIS SEMAGLUTIDE 3 MG VS. PLACEBO SEMAGLUTIDE 7 MG VS. PLACEBO SEMAGLUTIDE 14 MG VS. PLACEBO Difference in HbA1c at week 26, ITT 0.6%, p<0.001 0.9%, p<0.001 1.1%, p<0.001 Difference in HbA1c, on-treatment 0.7%, p<0.001 1.2% p<0.001 1.4%, p<0.001 Difference in weight loss at week 26, ITT 0.1 kg 0.9 kg 2.3 kg, p<0.001 Difference in weight loss at week 26, 0.2kg 1 kg, p<0.05 2.6 kg, p<0.001 on-treatment Source: Biomedtracker, Novo Nordisk grace Novo with pricing flexibility above that of current orals and up At the ADA meeting, Novo Nordisk presented a post hoc analysis to that of injectables, depending on Novo’s chosen price vs volume from the SUSTAIN-7 study, showing that Ozempic provided greater approach,” Deutsche Bank analyst Tim Race said in a June 20 note. weight reductions compared to Trulicity across levels of body mass “We continue to believe oral-[semaglutide] has the potential to index. Since launching in the US a few months ago, the company is become a >$5bn blockbuster product and should allow Novo to in the “fortunate position” of having more than 50% coverage in com- grow in the higher margin GLP-1 diabetes segment for the coming mercial and Medicare plans, Thomsen said. Globally, the company years,” Race added. still expects sales of at least DKK1bn ($157m) or more this year and Evercore ISI analyst Umer Raffat said in a June 20 note that PIO- says that the GLP-1 market growth is healthy in the US – above 20%. NEER 4 is “critical for commercial positioning” and that the outcome is Ozempic now has over 10% of new-to-brand scripts. likely as good as the company could have hoped for. In a June 21 note, Societe Generale analyst Florent Cespedes After proving to be as good if not better than Victoza on blood warned of the risk of oral semaglutide cannibalizing Victoza, which sugar lowering and weight loss, oral semaglutide is a very compel- accounts for 20% of company sales. However, Hobbs told Scrip that ling offering, Raffat said. he doesn’t see oral semaglutide competing with either Victoza or Ozempic, rather a new market will open up for people who need the WANTED: CV OUTCOMES DATA robust A1c lowering and weight loss possible with a GLP-1 agonist When it comes to competing with other oral drugs, semaglutide and haven’t had access to it. needs to be tolerable and also demonstrate a cardiovascular benefit, “We really believe that there are a lot of type 2 patients out there as SGLT2 inhibitors have proven an outcomes benefit. that could benefit from GLP-1 and are not getting it. We want to Nausea has been the main side effect of concern with semaglu- expand that number of patients who can achieve the benefits,” tide relative to oral classes. Novo noted during its call that the rates Hobbs said. of nausea in pivotal trials reported so far ranged from 16% to 21%, Meanwhile, Lilly is moving forward with higher dosing of Trulicity which is on par or lower than other GLP-1 agonists on the market. in a bid to boost blood sugar and weight loss. The drug is currently Outcomes data are coming soon. The PIONEER 6 cardiovascular approved at doses of .75 mg and 1.5 mg. outcomes study comparing oral semaglutide against placebo in The company presented Phase II data at the ADA meeting for two 3,176 patients is due to report this year, along with the rest of the higher doses: 3 mg and 4.5 mg. In the trial, three doses – 1.5 mg, 3 mg PIONEER program. and 4.5mg – were tested against placebo over 18 weeks. Ozempic demonstrated a 26% reduction in major adverse car- “We believe that investigation of additional doses for Trulicity can diovascular events in the SUSTAIN-6 study, but the company said at provide an important choice for patients,” Brad Woodward, senior the time the data were released that it would need a larger, longer medical director at Lilly Diabetes, said in an interview. outcomes study post-approval in order to get a claim for a cardiovas- Commenting on the Phase II data, Biomedtracker analysts said that cular benefit. while higher doses of Trulicity were associated with numerically great- The company now says that if PIONEER 6 is positive, the data along er reductions in A1c and body weight compared with the 1.5 mg with SUSTAIN-6 may be enough to support a cardiovascular claim dose, it is not quite clear yet whether their profile will match Ozempic. for both products. Novo also said that following discussions with the “On tolerability, the 3 mg dose had nausea and vomiting that were FDA, it no longer plans to run a large outcomes study of Ozempic. close to 1.5 mg, the 4.5 mg dose had rates of nausea that were appre- Instead it will run a large outcomes study of oral semaglutide and ciably higher (30.3% compared to 22.2%), with only a slight numeri- the results could support a claim for both products. This study will cal increase in vomiting,” Biomedtracker analysts commented. start enrolling in 2019. Lilly’s Phase III AWARD-11 study is evaluating the higher doses on a much larger scale, and the company aims to share results with regu- IMPACT ON LILLY’S TRULICITY latory authorities next year. If oral semaglutide was the only key launch for Novo, the pivotal data “Overall, it is probably worthwhile for the company to have started reports would matter a lot to Lilly’s competing Trulicity – but that’s a Phase III trial with higher doses to narrow the gap with semaglutide not the case, Evercore ISI’s Raffat said. somewhat, but injectable semaglutide may retain a moderate ad- Instead, Novo is very focused on the weekly Ozempic, and that works vantage,” Biomedtracker analysts said. in Lilly’s favor because it forces Novo into segmenting the market into There will also be increased competition from oral semaglutide, daily use with oral semaglutide vs. weekly with Ozempic and Lilly has a they added. market position in that weekly GLP-1 segment, the analyst said. Published online 30 June 2018 scrip.pharmaintelligence.informa.com 6 July 2018 | Scrip | 19 RESEARCH & DEVELOPMENT

AstraZeneca Looks To Deliver On Its Promises In Oncology JESSICA MERRILL [email protected]

straZeneca PLC has a budding on- cology portfolio that includes four Anew medicines launched since 2015 and more on the way. The company is fo- cused on competing against market-lead- ing PD-1/L1s in lung cancer, expanding the PARP inhibitor Lynparza (olaparib) beyond women’s cancer, building out a new hema- tology franchise and figuring out what com- binations of drugs will provide the most du- rable benefits in the future. The UK drug maker has a heritage in oncology and was ahead of its time with the launch of the targeted cancer drug Iressa (gefitinib) in 2003 – though it took time to clarify the drug’s role. But Astra- Zeneca has been better known for selling primary care blockbusters like Crestor and Tagrisso (osimertinib), the first-generation as VP for specialty care for AstraZeneca in Nexium, both now generic, and Symbi- EGFR inhibitor Iressa, and a portfolio of older the US, which included oncology at the cort for asthma. Increased investment in legacy products, mainly hormone therapies time. He joined AstraZeneca from Soriot’s oncology has been a priority under the like Faslodex,Zoladex and Casodex. alma mater. Roche in 2014, where Fredrick- leadership of CEO Pascal Soriot, and that Tagrisso still has plenty of room to grow, son managed oncology in Spain. In his cur- is starting to deliver a changing portfolio having received FDA approval for frontline rent role, he is accountable for AstraZeneca’s mix. (Also see “AstraZeneca Under Soriot: non-small cell lung cancer (NSCLC) in pa- commercial performance in the top eight Progress Report” - Scrip, 14 Jul, 2017.) tients with an EGFR mutation in April. (Also markets: the US, Japan, China and top five Oncology remains the company’s small- see “Keeping Track: A Fresh Wave Of Approv- European countries. est business unit behind cardiovascular/ als” - Pink Sheet, 22 Apr, 2018.) The legacy Fredrickson sees the four marketed growth metabolic and respiratory disease, but it products help to buffer the cancer portfolio, drivers as the foundation to build AstraZen- is the fastest growing. Oncology gener- accounting for more than half of sales, but eca into an oncology powerhouse. “We have ated sales of $4.02bn in 2017, representing the pressure is on AstraZeneca to build new the life cycle programs, [and] we can now be- growth of 19% and accounting for 20% big-ticket brands. None of the company’s gin to build around them to turn them into of the company’s consolidated revenues. cancer drugs crossed the blockbuster rev- significant, important franchises,” he said. “I Sales of respiratory drugs declined 1% and enue threshold in 2017. can see line of sight into being a top three CV/metabolic, the largest business, de- oncology player based on those assets.” clined 10%. BLOCKBUSTERS IN THE MAKING The expansion in oncology is a big initia- The approval of AstraZeneca’s first-in- Exec VP and Global Head-Oncology Busi- tive and Fredrickson said his top priority is class PARP inhibitor Lynparza (olaparib) ness Unit Dave Fredrickson has an ambition delivering commercial success. “The way in January 2015 was the firm’s first oncol- to change that, however. “The commer- that we are building out our field force, ogy approval in 15 years, but it is close cial engine is really starting to deliver in an our market access, our medical affairs, all of to delivering on its promise to have five important way across our four marketed that is focused with an eye towards what is novel oncology approvals by 2020, with brands. I believe that with Lynparza, Tagrisso, needed to maximize for oncology,” he said. the subsequent approvals of its PD-L1 Imfinizi and Calquence, each of those has But the company’s ambition to become inhibitor Imfinizi (durvalumab) and BTK an opportunity to be a blockbuster brand, a top oncology player will face real com- inhibitor Calquence (acalabrutinib). An- if not a multi-blockbuster,” he said during an mercial challenges. For starters, AstraZeneca other drug, a first-in-class anti-CD22 im- interview at the American Society of Clinical shares profits on one of the most promis- munotoxin moxetumomab could soon Oncology meeting in early June. ing growth drivers in its portfolio, Lynparza, be on the market for hairy cell leukemia. Fredrickson was tapped to lead the com- with Merck & Co. Inc. under a 2017 col- In addition to the three newer drugs, the mercial oncology group in October 2017, laboration. AstraZeneca accepted a $1bn oncology portfolio also includes the top- moving over from president of AstraZeneca upfront payment in exchange while also seller, the third-generation EGFR inhibitor K.K. in Japan and having previously served granting Merck shared rights to the MEK in-

20 | Scrip | 6 July 2018 © Informa UK Ltd 2018 RESEARCH & DEVELOPMENT

hibitor selumetinib. (Also see “A Whopper Of “We are the only PD-1/L1 in the Stage tumor sequencing work to better target po- A Deal: AZ Hands Half Of Lynparza To Merck” III setting, so today what we compete tential combinations to different patients. - Scrip, 27 Jul, 2017.) against is active surveillance, which is The company is evaluating new opportu- When it comes to Imfinizi, the company nothing,” he said. “That’s not to make it nities in IO, for example, around the innate was fifth to market and is facing fierce sound easy, because we have a big edu- immune system and the tumor-associated competition from the other PD-1/L1 inhibi- cational gap in front of us … but in Stage macrophages in the tumor microenviron- tors, especially in the biggest commercial III we have at least a two-year head start ment that can inhibit tumor-infiltrating lym- market, NSCLC: Merck’s Keytruda (pem- over any of the competitors.” phocytes to attack and kill tumors. brolizumab), Bristol-Myers Squibb Co.’s AstraZeneca also hopes to add an indica- But it is also digging in other areas as well, Opdivo (nivolumab) and Roche’s Tecentriq tion for advanced NSCLC as well, though it she said, pointing to DNA damage repair, (atezolizumab), as well as Pfizer Inc./Merck has faced setbacks with an IO/IO combina- where the company has had success with KGAA’s Bavencio (avelumab). tion it hoped would give it a leg up versus Lynparza. AstraZeneca has strategically kept AstraZeneca has embraced a come-from- the competition. Earlier this year, the initial a focus on small molecule cancer drugs, and behind strategy, forgoing the lead indica- results of the ARCTIC study failed to show a thinks it has an industry-leading portfolio in tions for the class to prioritize development PFS or survival benefit in advanced NSCLC DNA damage response. in untapped indications. (Also see “AstraZen- patients treated with a combination of Im- “IO is a paradigm-changing, massive eca’s Imfinzi Scores First Early Lung Cancer finzi and AZ’s CTLA-4 inhibitor tremelimum- event in cancer that we are still riding the Approval” - , 16 Feb, 2018.) ab. (Also see “ARCTIC Chill Descends On As- wave of, but it is not the only thing that is But the immuno-oncology (IO) playing traZeneca’s Imfinzi/Treme Combo In NSCLC” important,” Galbraith said. “You don’t hatch field is rough, and as AZ and BMS have seen - Scrip, 24 Apr, 2018.) all your eggs just in that one basket, and I some clinical setbacks, Merck is solidifying Another study testing the combination think we are different in that respect.” its lead. (Also see “Merck’s Keytruda Enjoys in metastatic NSCLC, MYSTIC, disappointed She highlighted several early-stage on- Clean Sweep In Lung Cancer, At Bristol’s Ex- when it failed to show a benefit on PFS last cology candidates that are being studied pense” - Scrip, 17 Apr, 2018.) It was the big year, but the study is continuing, with over- in combination with Imfinzi, including the headliner at ASCO with the release of new all survival data anticipated in the second small molecule adenosine A2A receptor data on Keytruda in lung cancer showing half of the year. The trial is evaluating Imfinzi antagonist AZD4635, the anti-CD73 an- the drug resulted in benefits in patients as monotherapy as well. (Also see “MYSTIC tibody oleclumab and anti-NKG2A anti- as monotherapy and in combination with Misses: Devastation For AstraZeneca As Im- body monalizumab. chemotherapy, regardless of PD-L1 muta- finzi Fails PFS Endpoint In NSCLC” - Scrip, 27 tion burden. (Also see “Merck’s Keytruda Jul, 2017.) Another Phase III study, POSEI- LEADING THE WAY IN PARP Monotherapy May Get Stuck With Small Role DON, is evaluating Imfinzi with and without AstraZeneca and partner Merck have big ex- In First-line Lung Cancer” - Scrip, 4 Jun, 2018.) tremelimumab plus chemotherapy, with pansion plans for Lynparza, which was the data expected in 2019. first PARP inhibitor approved by the FDA and IMFINZI: WINNING IN STAGE III The combination setback AstraZeneca is now the leading PARP inhibitor of three on AND FUTURE EXPANSION has faced is not so different from what oth- the market in terms of sales. It’s also the only Imfinizi scored an FDA approval for Stage ers in the industry have faced in the last year, PARP inhibitor approved in breast cancer as III NSCLC in patients whose disease has as disappointing data has read out from IO/ well as ovarian cancer, following the FDA not progressed on concurrent chemo- IO combination trials across the spectrum. approval in January in BRCA-positive breast therapy in February based on positive One of the big themes at ASCO this year cancer. (Also see “Lynparza Gets First Mover progression-free survival data, and up- was how industry has absorbed those dis- Advantage In BRCA-Positive Breast Cancer” - dated data from the PACIFIC trial released appointments; IO combinations with target- Scrip, 15 Jan, 2018.) in May also showed an improvement in ed therapies and chemotherapy impressed, “I think we have the best-in-class PARP overall survival. (Also see “PACIFIC Pays Off and companies continue to look for the inhibitor, so that’s one of the things that’s Again For AZ With Imfinzi Lung Cancer OS next potential combinations. (Also see most exciting, and we have the deepest Success” - Scrip, 25 May, 2018.) “ASCO 2018: Optimism As Industry Resets And and broadest development program,” Gal- The approval is a win for AstraZeneca, as Looks To What Is Next” - Scrip, 4 Jun, 2018.) braith said. The companies are looking to- the company is the only PD-1/L1 inhibitor Fredrickson said the company is working ward prostate cancer next, and announced approved for Stage III NSCLC. The challenge to improve how it evaluates combinations positive data from a Phase II study testing Lynparza in combination with is that three other checkpoint inhibitors early on before moving into large Phase III Johnson & Johnson’s Zytiga (abi- have been approved for Stage IV NSCLC that studies like it did with Imfinzi/tremelim- raterone) versus abiraterone alone, show- has spread, which encompasses a broader umab. “Instead of picking one combination ing improvements in PFS for the first time patient population, since patients with lung and moving forward with it, it’s how do we in metastatic castration-resistant prostate cancer are typically diagnosed late. get multiple different ones and pick the best cancer. (Also see “As A New Rival Approaches, Fredrickson is bullish on the opportunity ones,” he said. PARP Makers Look To Carve Out Their Niche” - in Stage III lung cancer because it is a poten- AstraZeneca’s Head of Early Stage On- Scrip, 7 Jun, 2018.) tially curative setting, compared to meta- cology Susan Galbraith said the company static lung cancer. is doing more platform-based studies and CONTINUED ON PAGE 23 scrip.pharmaintelligence.informa.com 6 July 2018 | Scrip | 21 PIPELINE WATCH

Scrip’s weekly Pipeline Watch tabulates the most recently reported late-stage clinical trial and regulatory developments from the more Click here for the entire pipeline than 10,000 drug candidates currently under active research worldwide. with added commentary: http://bit.ly/2mx4jY3

Selected clinical trial developments for the week 22–28 June 2018

LEAD COMPANY/PARTNER COMPOUND INDICATION COMMENTS PHASE III SUSPENDED interstitial cystitis/ Aquinox Pharmaceuticals Inc. rosiptor LEADERSHIP 301; primary endpoint missed. bladder pain syndrome PHASE III RESULTS PUBLISHED castration-resistant pros- Astellas PharmaInc./Pfizer Inc. Xtandi (enzalutamide) PROSPER; NEJM, June 28, 2018. tate cancer Hutchison MediPharma Ltd. fruquintinib colorectal cancer FRESCO; JAMA, June 26, 2018. PHASE III INTERIM/TOP-LINE RESULTS Acceleron Pharma Inc./ myelodysplastic luspatercept MEDALIST; met primary and secondary endpoints. Celgene Corp. syndorome Global Blood Therapeutics Inc. voxelotor sickle cell anemia HOPE; primary endpoint achieved. Korsuva (difelikefalin), pain during abdominal Cara Therapeutics Inc. Met primary endpoint, reducing pain and PONV. intravenous surgery Boehringer Ingelheim GMBH/ Jardiance (), diabetes, type 1 EASE-2, -3; positive top-line data. Eli Lilly & Co. with insulin Farxiga (dapagliflozin), AstraZeneca PLC diabetes, type 1 DEPICT-2; improved glycemic control. with insulin Tecentriq (atezolizumab) small cell lung cancer, Roche IMpower133; improved overall survival and PFS. plus chemo extensive stage Repatha (), diabetes, type 2 and Amgen Inc. BANTING; reduced cholesterol. monthly dyslipidemia hypoglycemia in diabetes, Xeris Pharmaceuticals Inc. , rescue pen Positive data. type 1 radiographic axial COAST-W; met primary and major secondary Eli Lilly & Co. Taltz () spondyloarthritis endpoints. PIONEER 3; reduced weight, HbA1c levels in long- Novo Nordisk AS semaglutide, oral diabetes, type 2 term study. ABP710, biosimilar Amgen Inc. rheumatoid arthritis Non-inferior to Remicade. infliximab ovarian cancer, first-line AstraZeneca PLC/Merck & Co. Inc. Lynparza (olaparib) SOLO 1; PFS improved. maintenance Pabal (carbetocin), acute hemorrhage after Ferring BV/Merck & Co. Inc./WHO CHAMPION; prevented excessive bleeding. heat stable childbirth UPDATED PHASE III RESULTS Biohaven Pharmaceuticals Holding migraine Study 301, 302; relieves pain, restores function. Co. Ltd. Edge Therapeutics Inc. EG-1962 subarachnoid hemorrhage NEWTON 2; clinical benefits seen. Emagality episodic Eli Lilly & Co. Positive clinical results. (-gnlm) prevention Farxiga (dapagliflozin), AstraZeneca PLC diabetes, type 1 DEPICT-1; reduced glycemic variability. with insulin Zynquista (sotagliflozin) Inc./Sanofi diabetes, type 1 inTandem; reduced A1C levels. with insulin Duchenne muscular Catabasis Pharmaceuticals Inc. edasalonexent MoveDMD; signs of disease slowing. dystrophy Novo Nordisk AS semaglutide, oral diabetes, type 2 PIONEER 2,4,7; updated clinical data. Ibrance (palbociclib) with HR+, HER2- metastatic Pfizer Inc. PALOMA-3; positive trend in overall survival data. fulvestrant breast cancer Source: Biomedtracker

22 | Scrip | 6 July 2018 © Informa UK Ltd 2018 RESEARCH & DEVELOPMENT/APPOINTMENTS

CONTINUED FROM PAGE 21 chronic lymphocytic leukemia. Data in CLL approval by September. Positive data from A large Phase III program in prostate can- are anticipated in 2019. an 80-patient Phase III study presented at cer is now in the works, though AstraZeneca “What we really wanted to do is get ASCO showed treatment resulted in a 75% also said it will speak with the FDA about the quickly to market and get an opportunity objective response rate and 41% complete Phase II results. Another Phase III program in for physicians to have experience with the response rate. combination with Imfinzi is also under way medicine and really pave the way for what Moxetumomab would also be AstraZene- in ovarian cancer. is the larger opportunity, which is the CLL ca’s first ADC product on the market, an area market,” Fredrickson said. AstraZeneca has of research in which the company is invest- BREAKING INTO BLOOD CANCER added a new sales team and ramped up ing more broadly. In hematology, the company has built a medical affairs. AstraZeneca also made an early move to commercial team to support the launch “We’ve hired a great sales force. We’ve got get into good position as IO extends from of Calquence, which was approved by the deep hematology experience,” he said. “We solid tumors into hematology, through a FDA in October as a second-line option for are well aware of the fact that people who are broad alliance with Celgene, looking to the the rare cancer mantle cell lymphoma. (Also good at solid tumor oncology are different hematology leader as a way to gain exper- see “AstraZeneca’s Calquence Steps Into Blood from those that understand hematology.” He tise as it built in the field. Cancer Ring With Mighty Imbruvica” - Scrip, 31 said the company is “absolutely” interested in It’s still early days for those efforts, but Oct, 2017.) The launch marked AstraZeneca’s expanding further into blood cancers, with AstraZeneca has made some big strides entry into blood cancers, where the com- several drugs in early development. filling out its commercial cancer portfolio. pany will compete initially against Johnson A second product is already poised to en- Now, continuing to push its pipeline, turn- & Johnson/AbbVie’s blockbuster first-in-class ter the hematology portfolio later this year, ing new launches into blockbuster brands BTK inhibitor Imbruvica (ibrutinib). moxetumomab, an anti-CD22 antibody and uncovering the best combinations for MCL is a niche indication, but it presents drug conjugate (ADC) for relapsed hairy the future will be the key to seeing how the an opportunity for AstraZeneca to ease into cell leukemia, for which there are no cur- company succeeds in building an oncology the market. The company has its eye on a rent treatments. The BLA has been granted specialty from the ground up. much larger commercial opportunity in a by the FDA and could see Published online 27 June 2018

Deborah Dunsire has been appointed Gene therapy developer Orchard Thera- maceuticals, has joined Sangamo Thera- president and CEO of Lundbeck, as of peutics has appointed Jim Geraghty as peutics’ board of directors. Previously she Sept. 1, 2018. Anders Götzsche, who had chairman of the board of directors, replac- was senior vice president, global medical been acting as interim CEO and CFO since ing Ben Auspitz, partner at F-Prime Capital. affairs and global dermatology head at November 2017, will resume his position as Jim held leadership positions at Genzyme, Allergan, and before that held leadership CFO of the Danish neuroscience specialist. including founding president and CEO of positions at AstraZeneca and Bristol-My- Most recently Dunsire was president and Genzyme Transgenics, and was also senior ers Squibb. CEO of Xtuit Pharmaceuticals. She was pre- vice president, North America strategy and viously CEO of Forum Pharmaceuticals and business development at Sanofi. Research directors from the Broad Institute, Millennium Pharmaceuticals, both before Merck Research Laboratories and Celgene and after it was acquired by Takeda. Another former Genzyme executive, Andre have joined protein stability-focused start- Turenne, has been appointed as president up Cedilla Therapeutics as vice presi- Scott Chappel has been named chief scien- and CEO of Voyager Therapeutics. His dents. Dale Porter, who most recently tific officer of Belgian cancer immunotherapy most recent role was senior vice president, directed oncology drug discovery research firm iTeos Therapeutics. Previously he was global head, business development and li- at the William Sellers Lab of the Broad Insti- a founder and chief technology of Surface censing responsible for partnering activities tute of MIT and Harvard, and who previous- Oncology, and before that was a founder across all business units at Sanofi.Steven ly worked at Novartis, has been appointed and CSO of Arteaus Therapeutics (acquired Paul is retiring as president and CEO but will vice president of biology. Iván Cornella- by Eli Lilly) and Tokai Pharmaceuticals. The continue to serve on the board of directors Taracido joins as vice president of prot- company has also appointed David Hallal, and science and technology committee. eomics and chemical biology; he was for- former CEO of , as merly director chemical biology at Merck chairman of its board of directors, and Tim Cevec Pharmaceuticals has appointed Research Laboratories. Eric Schwartz, Van Hauwermeiren, CEO of argenx, as in- gene therapy specialist J. Fraser Wright, former executive director of chemistry at dependent non-executive director. chief technology officer, gene therapies at Celgene, will be vice president of drug dis- Axovant and scientific co-founder and for- covery at Cedilla, which was launched in Astellas Pharma Inc has promoted Yukio mer CTO at Spark Therapeutics, to its scien- 2018 by Third Rock Ventures and is based Mastui, hitherto head of EMEA operations, tific advisory board. in Cambridge, Massachusetts. The com- to the position of chief commercial officer. pany hopes to broaden the reach of small Dirk Kosche, formerly president of Novartis Karen Smith, who most recently served molecules by generating therapeutics that Pharma KK in Japan, has joined the com- as executive vice president, global head degrade protein targets as their primary pany to head EMEA operations. R&D and chief medical officer of Jazz Phar- mechanism of action. scrip.pharmaintelligence.informa.com 6 July 2018 | Scrip | 23 Recognising the best in the global generics and biosimilars industries.

Cocktail Reception & Awards Presentation Tuesday, 9 October 2018 Palacio Municipal de Congresos Madrid, Spain

Sponsor, Enter, Join us! Find out more about sponsoring or entering an Award and joining us on the night.

Presented by Sponsored by

In association with

Visit: www.pharmaintelligence.informa.com/ggba Email: [email protected] | Call: +44 (0) 1564 777 550

JN1113 GGB Awards 2018 Advert UKA4.indd 1 2018/05/25 10:14