'Flexible Pricing' for Kisqali to Compete Against Pfizer

Company Focus Expert view Changes to NICE Timelines Analysts aren’t surprised to see the Hemophilia patients are loyal to New rules will allow NHS England Danish diabetes giant stalking brand-name clotting factors but a to delay some new drugs for up to Global Blood Therapeutics (p5) shakeup may be coming (p8) three years (p15)

24 March 2017 No. 3846

Scripscrip.pharmamedtechbi.com Pharma intelligence | informa Novartis is looking to differentiate through its “flexible price structure.” Bill Hinshaw, head of Novartis US Oncol- ogy, revealed the price structure during a conference call with reporters on March 13, explaining that the wholesale acquisi- tion cost (WAC) for a 28-day cycle (21 days on treatment followed by seven days off) is $10,950 for the 600 mg once-daily dose, $8,760 for the 400 mg dose and $4,380 for the 200 mg dose; a patient assistance program will be available for both insured and uninsured patients. The drug will be shipped to specialty and retail pharmacies as soon as March 14. Hinshaw noted that Kisqali pricing re- sponds to the need for prescribers to adjust dosing based on known cardiovascular, liver Shutterstock: Lightspring Shutterstock: and hematologic side effects. Some cases of QT prolongation, AST and/or ALT elevation and high-grade neutropenia were reported Novartis Sets ‘Flexible Pricing’ For in the Phase III MONALEESA-2 trial, which was the basis for the US FDA approval. Novartis has formulated Kisqali in 200 mg Kisqali To Compete Against Pfizer capsules, making it easier for oncologists to MANDY JACKSON [email protected] lower dosing to the required 400 mg or 200 mg doses as needed to manage the CDK4/6 Novartis has packaged and priced Kisqali – the second CDK4/6 inhibitor approved in inhibitor’s effects on heart rhythm, liver the US – to compete with Pfizer’s Ibrance, which made the mechanism of action the function and neutropenia – three items that standard of care in untreated metastatic HR+/HER2- breast cancer. prescribers must measure at certain points before and during treatment. ovartis AG’s Kisqali (ribociclib; dent kinase 4 and 6 (CDK4/6) inhibitors. Hinshaw noted that Kisqali dosing can LEE011) was approved on March The mechanism quickly became the front- be reduced without treatment interruption N13 as the second drug of its kind in line standard of care for post-menopausal – a luxury that oncologists don’t have with the first-line setting for certain breast cancer women with hormone receptor (HR)- Pfizer’s Ibrance, which is formulated in 125 patients in the US – and it could have com- positive/human epidermal growth factor mg, 100 mg and 75 mg capsules and was petition from a third next year – so the com- receptor-2 (HER2)-negative advanced or launched in early 2015 with a WAC price pany has packaged and priced its product metastatic breast cancer – the populations per cycle of $9,850. Ibrance pricing in ex-US to compete with Pfizer Inc.’s first-to-market for which Kisqali and Ibrance are approved. markets has come under pressure, particu- Ibrance (palbociclib). Similar profiles for the two drugs were seen larly in the UK where its cost may limit ac- Both drugs and Eli Lilly & Co.’s Phase III in Phase III clinical trials that were stopped cess. The drug is under review in Japan. candidate abemaciclib are cyclin-depen- early for positive efficacy, so its appears that CONTINUED ON PAGE 7

BROUGHT TO YOU BY THE EDITORS OF PHARMASIA NEWS, START-UP AND SCRIP INTELLIGENCE IN THIS ISSUE 5

Competition iTeos: IO For Hemophilia Therapies For Franchises Hot And Cold Tumors Novo After Global Blood Therapeutics? 8 21

COVER / Novartis Sets ‘Flexible Pricing’ For Kisqali To Compete from the editor Against Pfizer [email protected] 3 Mylan Clears Runway For US Herceptin Biosimilar Launch

The term ‘microbiome’ has only really taken on any 4 Blood Cancer Sector More Competitive After Keytruda Approval kind of currency since the early part of this century, but in the past few years it has become a regular 5 Company Focus: Is Anemic Growth Sending feature of biopharma discussions. Referring to the Novo Nordisk After Global Blood Therapeutics? totality of the micro-organisms (and their genetic material) in a particular environment, the human 6 Ackman ‘Throws In The Towel’ – What’s Next For Valeant? microbiome (and most commonly that of the gut) is 7 Threshold/Molecular Templates: The Power Of Two increasingly the target of therapeutic R&D programs, and the raison d’être for a growing band of start-ups. 8 Expert View: Competition Coming For Hemophilia We have created an infographic (p14) on the indus- Franchises, But Will Patients And Payers Embrace try’s efforts in the field, which has attracted around New Drugs? $1bn in company funding since 2011. As with any 11 R&D Bulletin hot topic, there are voices of caution and dissent; one panellist in a partnering function at a big pharma 12 Research & Development: AstraZeneca’s Lynparza memorably declared at BIO last year that she might Looks To Hang On To Lead herself get C. diff if yet another microbiome proposi- 13 Editas Deal Opens Allergan’s Eyes To CRISPR tion crossed her desk. Scrip would like to hear the views of our readers: 14 Infographic: The Microbiome are you excited about the opportunity in this field? Or are you cautious about significant hurdles that 15 Pricing: NICE Appraisal Changes: A New Pricing Hurdle you feel are being overlooked? Drop me an email. 16 Business Bulletin

17 Company Focus: Lilly Eyes Top 10 Japan Ranking Built On Launches

18 FDA Moves On Endo’s Opana ER Unlikely To Sweep Up Other Opioids

exclusive online content 20 Policy & Regulation Briefs

21 Emerging Company Profile:iTeos: IO Therapies For Is Amgen’s FOURIER Enough For Physicians, Hot And Cold Tumors Payers To Expand Repatha Use? Detailed results presented at ACC show a reduction in risk of 22 Pipeline Watch major adverse cardiovascular events, but perhaps not at the level hoped for by payers. 23 Appointments http://bit.ly/2neial5

Finance Watch: Two New VC Funds Raise $500m; One New US IPO; And Galena’s ‘Strategic Review’ http://bit.ly/2nRAZbp

Deal Watch: Success Nets CytomX Another $200m From BMS, Up To $3.6bn For Milestones http://bit.ly/2nd2IVC @scripnews /scripintelligence

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2 | Scrip intelligence | 24 March 2017 © Informa UK Ltd 2017 HEADLINE NEWS

Mylan Clears Runway For US Herceptin Biosimilar Launch JESSICA MERRILL jessica [email protected]

Mylan NV could be the first manufacturer to launch a biosimilar logics Price Competition and Innovation Act’s (BPCIA) “patent dance” version of Roche’s blockbuster breast cancer treatment Herceptin is optional or mandatory and whether 351(k) sponsors must wait until (trastuzumab) in the US. The company has an application for a ver- licensure before providing 180-day notice of launch. sion of trastuzumab pending at FDA with a user fee date of Sept. There has not been much legal precedent yet related to biosimi- 3., and now the company has also cleared the crucial intellectual lars in the US, so it remains to be seen how the IP issue will evolve. property hurdle. There are many other versions of trastuzumab in development, and there is no guarantee that Mylan’s product, developed with partner ylan announced March 13 that it has reached a patent Biocon Ltd., will have a smooth regulatory review. Mylan updated in- settlement agreement and a licensing deal with Roche vestors on its pipeline during an investor overview March 1, highlight- Mrelated to patents for Herceptin. The global license will pro- ing biosimilars and complex small molecule drugs. The company said vide a clear path for Mylan to commercialize trastuzumab globally it has one of the broadest biosimilar pipelines in the industry, including (excluding Japan, Brazil and Mexico), the firm said. The catch is that a second product pending at FDA, a biosimilar to Amgen’s Neulasta the US launch timeline remains unknown. Mylan said the effective (pegfilgrastim), with an Oct. 9 action date. dates for launches in various markets under the agreement remain There are as many as 19 different formulations of trastuzumab in de- confidential, which means it is unclear how much, if any, delay Mylan velopment. Pfizer Inc. has completed Phase III testing of its formula and and Roche might have negotiated beyond the FDA action date. presented positive top-line results in December. Mylan, meanwhile, agreed to withdraw its pending inter partes re- Approved in 1998, Herceptin is a backbone therapy for the treat- view (IPR) challenges against two US patents for Herceptin held by ment of women with HER2-positive breast cancer. Herceptin gener- Roche’s Genentech unit (patents 6,407,213 and 6,331,415). ated CHF6.78bn ($6.73bn) in 2016. The drug is one of Roche’s top- Biosimilar sponsors face a tangled web of patent proceedings, which sellers, behind Rituxan (rituximab) and Avastin (bevacizumab), which are one of the biggest hurdles to getting more biosimilars to market. are also expected to face biosimilar competition, creating substantial More clarity on the legal proceedings could come in 2017. The US headwinds for the Swiss pharma. Roche introduced an antibody-drug Supreme Court agreed to hear a dispute between Amgen and Sandoz conjugate version, Kadcyla (ado-trastuzumab emtansine) in 2013. Inc. involving Sandoz’s Zarxio (filgrastim) related to whether the Bio- Published online 13 March 2017

scrip.pharmamedtechbi.com 24 March 2017 | Scrip intelligence | 3 HEADLINE NEWS

Blood Cancer Sector More Competitive After Keytruda Approval The US FDA approval of Keytruda in its first hematologic cancer indication will put Merck & Co in a position to compete with Bristol-Myers Squibb, whose own checkpoint inhibitor Opdivo gained a similar, but not identical, marketing approval in classical Hodgkin lymphoma last year.

JOHN DAVIS [email protected]

onfirmation that checkpoint inhibitors are beneficial in the ing patients, the median duration of response was 11.1 months treatment of blood-borne cancers has come from the US (ranging from zero to 11.1 months). Capproval of Merck & Co. Inc.’s anti-PD1 therapy Keytruda Keytruda is administered intravenously every three weeks until (pembrolizumab) for the treatment of patients with classical Hodg- disease progression or unacceptable toxicity, or up to 24 months in kin lymphoma refractory to other treatments, or who have relapsed patients without disease progression. This compares with a dosing after three or more prior lines of therapy. Previously the drug was schedule of every two weeks for Opdivo. only approved in solid tumors. Keytruda was discontinued due to adverse reactions in 5% of 210 The approval, announced March 14, is the first for Keytruda in a patients in the KEYNOTE-087 study, and treatment was interrupted hematologic malignancy, and Merck also highlighted that the addi- due to adverse reactions in 26% of patients. The most frequent se- tional indication is regardless of prior stem cell transplant or use of rious adverse reactions (>1%) were pneumonia, pneumonitis, py- Seattle Genetics Inc.’s Adcetris (brentuximab vedotin). The approval rexia, dyspnea, GvHD and herpes zoster. comes nearly a year after Bristol-Myers Squibb Co.’s checkpoint inhibitor Opdivo (nivolumab) was approved in the US for a similar The additional indication is regardless indication, although then the FDA specified that Opdivo therapy in relapsed and refractory classical Hodgkin lymphoma should of prior stem cell transplant or use of follow treatment with autologous stem cell transplant and post- transplant brentuximab vedotin therapy. brentuximab vedotin In Europe, Opdivo was approved for the classical Hodgkin lym- phoma additional indication in November 2016, while Keytruda is There are few other options for patients with classical Hodgkin in Phase III studies for classical Hodgkin lymphoma. lymphoma who do not respond to a stem cell transplant, or use of Interestingly, Opdivo has just been knocked back by the UK’s brentuximab vedotin. “Treating their disease becomes more chal- health technology assessment body, NICE, that asked in a prelimi- lenging,” commented Dr Craig Moskowitz, clinical director in the nary assessment released March 13 for a revision of cost-effective- division of hematologic oncology at the Memorial Sloan Kettering ness analyses versus standard of care, the use of UK data on stan- Cancer Center, in a Merck statement. dard of care, and data on the subsequent rate of allogeneic stem There are also far fewer patients with classical lymphoma; there cell transplant. That could allow Keytruda to catch up some ground are around 8,500 new cases reported every year in the US, with on the BMS drug, at least in the UK. around 1,120 deaths, with the condition affecting patients at a According to Datamonitor Healthcare senior analyst Dominique relatively young age, predominantly adolescents and young adults. Fontanilla, the US approval is positive news for Keytruda, but is un- Fortunately, nearly three-quarters of patients are cured with che- likely to have a major impact in terms of sales. Hodgkin lymphoma motherapy and/or radiation. is relatively uncommon, with DMHC estimating there were 18,770 In the past, the use of checkpoint inhibitors has been primar- diagnosed cases in 2014 in the US, Japan, and the five major EU ily focused on solid tumors such as non-small cell lung cancer. markets (France, Germany, Italy, Spain and the UK). Additionally, However, their use in blood cancers is now an active field of Keytruda’s and Opdivo’s approvals in the later line of treatments research, with for example Celgene Corp. and AstraZeneca PLC means the potential market size is even smaller. partnering on the development of the PD-L1 inhibitor dur- However, Merck has started a large Phase III study (KEYNOTE-204) valumab in hematologic cancers, and BMS studying Opdivo in comparing Keytruda to the current standard of care Adcetris in pa- multiple myeloma. tients with relapsed Hodgkin lymphoma, that could close any gap Merck also reported March 14 a three-month extension, to June between Keytruda and Opdivo, Fontanilla commented. 9, 2017, to the FDA’s target action date on its sBLA for Keytruda use Keytruda was cleared under the US’s accelerated approval regu- in previously-treated patients with advanced microsatellite instability- lations for use in adult and pediatric patients with refractory classi- high (MSI-H) cancer. MSI-H is seen in around 15% of patients with cal Hodgkin lymphoma (cHL), or who have relapsed after three or colorectal cancer, and Merck recently submitted additional data and more prior lines of therapy, based on the tumor response rate and analyses to the regulator, that was considered a major amendment the durability of that response in the KEYNOTE-087 study. In that necessitating a three-month extension to the review. Merck could be- study involving 210 patients, the overall response rate with Key- come one of the first companies to gain an approval for a checkpoint truda was 69% (95% CI: 62, 75) with a complete remission rate of inhibitor in colorectal cancer. 22% and a partial remission rate of 47%. Among the 145 respond- Published online 15 March 2017

4 | Scrip intelligence | 24 March 2017 © Informa UK Ltd 2017 COMPANY FOCUS

Is Anemic Growth Sending Novo Nordisk After Global Blood Therapeutics? STEN STOVALL [email protected]

Once high-flying Novo Nordisk has been drug emicizumab (ACE910) eroding sales sending out M&A signals as it seeks a so- of NovoSeven, and thus acting as a drag lution to weak growth, so analysts aren’t on 2018 and 2019 earnings.” NovoSeven surprised to see the Danish diabetes is Novo Nordisk’s aging hemophilia drug giant stalking US-based Global Blood whose sales have been sliding; the com- Therapeutics. pany doesn’t yet have strong commercial response after it decided in September ovo Nordisk AS’s long and steady fi- 2012 to discontinue the development of nancial run on self-generated diabe- vatreptacog alfa, a fast-acting recombi- Ntes and obesity products is flagging nant Factor VIIa analogue for hemophilia – and the Danish group has acknowledged patients with inhibitors which had been that it needs to revitalize its other product in Phase III trials and had been seen un- lines to generate fresh revenue growth – so til then as a replacement for blockbuster reports it is interested in California-based NovoSeven. Cherries Shutterstock: Global Blood Therapeutics Inc. have not sur- prised observers. GLOBAL BLOOD BOLT-ON? Reuters and Bloomberg, quoting un- So could Global Blood Therapeutics help ‘Novo Nordisk has avoided named sources, reported the South San the Danish group respond to its current acquisitions in the past, so Francisco-based sickle cell drug developer commercial gloom? has been approached by Novo Nordisk. The loss-making company was found- this is a change of direction Neither Global Blood nor Novo Nordisk ed in 2012 by Third Rock Ventures and for them’ would comment to Scrip on the reports, launched an IPO in Aug. 2014. Before me- but analysts say it makes sense for the Dan- dia reports of Novo Nordisk’s interest in it, ish group to actively look outside for a bolt Global Blood Therapeutics had a market on to help it diversify beyond its aging dia- value of around $1.2bn. betes franchise. It is developing drugs for blood-based FDA for treating patients with SCD and or- diseases including sickle cell disease (SCD) phan status in Europe. DIVERSIFICATION NEEDED and idiopathic pulmonary fibrosis. Ana- “It’s an interesting approach, chang- “I’m sure it’s a calculated risk; in this case lysts say acquiring the young company ing the affinity of hemoglobin for oxy- since Novo Nordisk’s diabetes business is would provide positive additions to Novo gen, but the data are still somewhat suffering, so they need to focus elsewhere Nordisk’s portfolio. Of immediate interest preliminary at this point,” BioMedTracker and this acquisition can help them strength- is its product candidate known as GBT440, analyst Peter Chang said, adding that the en their blood offerings. Novo has avoided a hemoglobin modifier that binds to he- drug did increase hemoglobin apprecia- acquisitions in the past so this is a change moglobin molecules. The oral, once-daily bly “and could well impact symptoms, of direction for them,” commented Steven therapy for sickle cell disease is in double- though the study was quite small and Muntner of Medtrack. blind Phase I/II clinical trialing and will en- there is only limited side effect informa- Rising competition and pricing pressures ter a pivotal Phase III study in SCD called tion so far.” in the US and elsewhere led Novo Nordisk HOPE by the end of 2017, according to Analysts said Novo Nordisk had alerted last October to slash its growth expecta- BioMedTracker. Like hemophilia, SCD is an the investment community last year dur- tions for 2017 and increase R&D efforts, an- orphan disease. ing its third quarterly earnings update that nouncing expansion into new therapy ar- Since oxygenated sickle hemoglobin it was thinking about M&A. eas and seek external deals for early-stage does not polymerize, Global Blood Thera- “They were looking to do bolt-on acqui- assets to bulk up its pipeline. peutics thinks GBT440 blocks polymer- sitions, which they said was more realistic Its outlook reduction last autumn sent ization and the resultant sickling of red than a large acquisition, and get slightly Novo Nordisk shares south. Berenberg an- blood cells. “With the potential to restore out of their core and add competencies, alysts Mar. 6 said, “Novo’s shares have not normal hemoglobin function and improve in addition to their growth in emerging recovered from the profit warnings issued oxygen delivery, GBT440 may be capable markets for diversification. So it does look by the group in 2016. It is clear from guid- of modifying the progression of SCD,” the like this would fit into their strategy in that ance that 2017 will be a slow year, and company says. GBT440 has both fast track sense,” Chang said. there is a risk of Roche’s new hemophilia and orphan drug designation from the Published online 13 March 2017

scrip.pharmamedtechbi.com 24 March 2017 | Scrip intelligence | 5 HEADLINE NEWS

Ackman ‘Throws In The Towel’ – What’s Next For Valeant? Valeant’s prospects were dim with or without Pershing Square’s continued backing, but at least one analyst says Ackman’s departure sends a signal that business won’t rebound at the Canadian specialty pharma any time soon.

JOSEPH HAAS [email protected]

he business outlook at Valeant Phar- portfolio, including recently approved pso- approvals, and a primary care effort behind maceuticals International Inc. is un- riasis drug Siliq (brodalumab). Valeant CEO key product Xifaxan to accelerate that prod- T certain at best and the sell-off by Joseph Papa expressed optimism about uct,” Nachman said. Pershing Square Capital Management of its Siliq’s potential to be a growth-driving prod- In a March 14 note on Pershing Square nearly 10% stake in the Canadian specialty uct for the company during its most recent Holdings, Jefferies analyst Matthew Hose pharma doesn’t necessarily make the situa- earnings call Feb. 28, but analysts aren’t ter- suggested that with Valeant’s stock having tion any worse – but only because Valeant’s ribly bullish on the product. fallen 95% from its peak price, the hedge prospects are so bleak to begin with. “Unsurprisingly, Valeant’s stock seems to fund’s investors “are likely to have attribut- Pershing Square, led by billionaire activist be reacting to the loss of [Ackman’s] vote ed little or no value to the remaining posi- investor Bill Ackman, had tied its fortunes to of confidence, but the fundamentals of the tion in Valeant.” He expects the divestiture Valeant in the past two years, going so far as business remain unchanged, from our per- to play out positively for Pershing Square. to increase its holdings in the firm as a com- spective,” Waterhouse told Scrip. “Restructur- bination of pricing pressure, accounting ing the debt maturities is a slight positive, CHOPPY WATERS questions and a heavy debt load catalyzed but management still has a lot of work to It’s been a stormy tenure at Valeant for Ack- an ongoing decimation of Valeant’s share do with asset sales or returning to growth man, who stage-managed the departure of price. Ackman aligned himself with the to climb out of the debt hole. Greater than Pearson – the exec who had overseen a long troubled biopharma, even testifying along- expected performance from Xifaxan or from string of acquisitions around already-on- side the embattled outgoing CEO Michael the launch of Siliq could offer some upside, market products or late-stage clinical can- Pearson before the Senate Aging Commit- but we’re skeptical for the time being.” didates to build up the company’s portfolio tee about the company’s practices last April. In a March 6 note on Valeant, Waterhouse – and his replacement with Papa, former All that changed March 13, as Pershing had said the specialty firm faces an exacer- CEO of Perrigo Co. PLC. The Senate Aging Square Holdings, the hedge fund’s publicly bated debt problem with “no room for er- Committee’s review of Valeant’s business traded security arm, revealed that it had sold ror.” The gastrointestinal drug Xifaxan (rifaxi- practices unveiled a set of correspondence off its entire interest in Valeant – more than min) faces near-term generic competition, between Ackman and the company in 27m shares and options – incurring a loss es- as does Jublia (efinaconazole), a topical which he urged the company to tell the full timated at between $3bn and $4bn. Inves- product for onychomycosis. Valeant earn- truth about its business relationship with the tors reacted predictably by further punishing ings will continue to contract, the analyst specialty pharmacy Philidor, adding that in- Valeant’s stock, which dropped an additional wrote, “due to the firm’s efforts to invest in vestors increasingly distrusted answers they 10.3% on March 14 to close at $10.86. All new product launches combined with de- were getting from Valeant management. told, the Laval, Quebec-headquartered firm clining sales from higher customer rebates Using terms like “brink of catastrophe” has seen its share price decline by approxi- and new generic competition on several and “death spiral,” Ackman told Valeant ex- mately 95% since peaking at $257 in 2015. high-margin products. With ongoing per- ecs in an October 2015 emails that their Offering its rationale for selling the formance below our expectations, we see staged conference call to try to manage shares now at a loss rather than maintain- few favorable options on the horizon.” controversies around price increases and ing in hopes of a business rebound, Persh- One possible move Valeant could make, the Philidor relationship had worsened ing Square said “the investment required a Waterhouse added, is to sell off the Bausch the situation. disproportionately large amount of time & Lomb Inc. eye care unit, whose legacy Still, Ackman testified alongside Pearson and resources. As a result, we elected to sell products continue to perform well. Theo- before the Aging Committee in April 2016, our investment and realize a large tax loss, retically, selling this business could bring to address reports that 30 of Valeant’s top- which will enable us to dedicate more time Valeant a solid price, he said. selling drugs had increased in price by an to our other portfolio companies and new BMO Capital Markets’ analyst Gary Nach- average of 78%. At the time, Ackman said investment opportunities.” man reads the Pershing Square decision to Pershing had been mistaken in taken a pas- mean that it determined turning Valeant sive investment role in the company, but ATTEMPTED RECOVERY around would take longer than expected asserted that frequent price increases were Analyst Michael Waterhouse of Morningstar and face even more hurdles than initially only “a small part of the business” at the time said Ackman’s departure at this point likely anticipated. “The timing of this decision is his company evaluated investing in Valeant. won’t have a major effect on Valeant’s future particularly noteworthy since new man- Still, Ackman increased his initial stake from prospects, which will be driven by getting agement is just beginning to implement a 5.6% to more than 9%, becoming second- out of debt, realizing solid returns by selling number of its strategic initiatives, including largest holder of Valeant stock. off assets and succeeding with the current asset sales to help pay down debt, pipeline Published online 14 March 2017

6 | Scrip intelligence | 24 March 2017 © Informa UK Ltd 2017 HEADLINE NEWS

CONTINUED FROM COVER Ibrance efficacy, however, since median In addition to its flexible price structure, PFS for the Pfizer drug in combination with Threshold/ Novartis also believes it can compete with letrozole was 24.8 months in the Phase III Molecular Pfizer in terms of convenience. Hinshaw PALOMA-2 study versus 14.5 months for le- pointed out that patients can take the drug trozole alone. Ibrance is approved for treat- Templates: The whenever they like, since – unlike Ibrance – ment in combination with letrozole as well it does not have to be taken with food. as in combination with the selective estro- Power Of Two gen receptor degrader fulvestrant for post- IBRANCE’S ADVANTAGE Although a vehicle for Molecular Tem- menopausal women who fail treatment Ibrance has a big and important advantage plates to take its Engineered Toxin Bodies with letrozole or other endocrine therapies. over Kisqali, of course, because it has been oncology platform public, the combined Safety also is not a major differentiator for on the market for two years, rapidly becom- company also will seek a pathway to ap- the two drugs. Like Kisqali, Ibrance has warn- ing a blockbuster product. Pfizer reported proval for Threshold’s evofosfamide for ings about cardiovascular and hematologic $2.14bn in 2016 Ibrance sales versus $723m pancreatic cancer in Japan. adverse events in its label – pulmonary em- in 2015 and Leerink analyst Seamus Fernan- A reverse merger between troubled bolism and neutropenia – with neutropenia Threshold Pharmaceuticals Inc. and dez recently forecast $3.25bn in 2017 sales, specifically identified as a side effect that may privately held Molecular Templates rising to $6.83bn by 2021. require prescribers to reduce the Ibrance Inc. will take the latter company, fo- Novartis has its own blockbuster hopes dose. The label has separate dose-lowering cused on new a class of cancer drugs for Kisqali – one of a dozen potential $1bn- instructions for non-hematologic events. with potential in immuno-oncology, plus sellers in its research and development public. However, the combined pipeline – but Pfizer may very well maintain ADDITIONAL TRIALS ONGOING company remains committed to the a strong lead in the market for CDK4/6 in- Outside of their approved labels, Pfizer’s former’s evofosfamide, which was hibitors. US oncologists have had two years drug also has a lead over Novartis’s product considered dead and buried after a to get acquainted with Ibrance, during in the adjuvant setting where the Phase III pair of Phase III failures in late 2015. which time it has become part of the stan- PALLAS study began in August 2015 evalu- The two firms announced their dard of care in first-line treatment of meta- ating treatment with Ibrance plus an endo- merger during an investor call on static HR+/HER- breast cancer. crine therapy for at least five years versus March 17, outlining an all-cash Also, with remarkably similar data for the standard endocrine adjuvant therapy, such transaction approved by both boards two drugs, it could be difficult for Novartis as letrozole. Novartis said on March 13 that of directors that will result in a new to switch prescribers from Ibrance to Kisqali, it recently began its own adjuvant study, company called Molecular Templates unless the Swiss pharma can win over both which will enroll 2,000 patients. Inc., headquartered in Austin, Texas. oncologists and payers with its flexible dos- Current Molecular Templates CEO ing and pricing strategy. Ongoing Phase III trials for Kisqali in- clude MONALEESA-3, which combines the Eric Poma, a former ImClone Systems Kisqali plus the aromatase inhibitor/en- Inc. executive, will become CEO of the docrine therapy letrozole reduced the risk CDK4/6 inhibitor with fulvestrant compared with fulvestrant alone in postmenopausal new company, while Threshold CEO of death by 44% versus letrozole alone at Barry Selick will take one of Thresh- women with HR+/HER2- advanced breast the first interim analysis for MONALEESA-2, old’s two seats on the board and serve cancer who have not been treated with or when the Phase III trial was stopped for ef- as chairman. were treated only once with endocrine ther- ficacy. The FDA relied on data from that in- Selick said the decision to merge with apy. In MONALEESA-7, Kisqali plus endo- terim analysis in its approval decision. Molecular Templates was reached after crine therapy and goserelin are being com- MONALEESA-2 results included in the a lengthy process of reviewing pos- pared to endocrine therapy and goserelin drug’s label show that median progression- sible strategic directions for Thresh- alone in premenopausal women with HR+/ free survival (PFS) hadn’t been reached in the old, which considered more than 100 Kisqali/letrozole arm as of the first interim HER2- advanced breast cancer who have alternatives. review, but the median PFS in the letrozole- received no prior endocrine therapy. Data Following the merger, expected to only arm was 14.7 months (p<0.0001). PFS from both studies are expected around the close during the second quarter, exist- ranged from 13 to 16.5 months in the com- end of 2017 or early 2018 and could support ing Molecular Templates’ sharehold- parator arm of the study versus a minimum a supplemental filing with the FDA in 2018. ers will own nearly 66% of the new PFS of 19.3 months in the Kisqali group. Lilly hopes that even with its third-to- company, with Threshold investors Novartis reported that median PFS market position, its CDK4/6 inhibitor abe- owning 34%. reached 25.3 months in the combination maciclib will be able to grab market share [email protected], 17 March 2017 arm and 16 months in the letrozole-only from its predecessors based on potentially arm after an additional 11 months of data improved safety. The company thinks that were collected. Overall survival data are not its more selective drug could allow for con- Read about the next- generation potential in mature, so the company expects to report tinuous dosing without the need to inter- immunotherapy here: those results at a later date. The data to date rupt therapy due to severe neutropenia. http://bit.ly/2nidOsT do not show a substantial difference from Published online 14 March 2017 scrip.pharmamedtechbi.com 24 March 2017 | Scrip intelligence | 7 EXPERT VIEW

Competition Coming For Hemophilia Franchises, But Will Patients And Payers Embrace New Drugs? MANDY JACKSON [email protected]

Roche’s emicizumab, Alnylam’s fitusiran Top Hemophilia Franchises By A once-weekly injection of emicizum- and multiple gene therapies may soon 2016 Sales* ab was an effective prophylactic therapy steal market share from established clot- for hemophilia A patients enrolled in HA- Shire (Baxalta): $3.7bn ting factors sold by Shire, Novo Nordisk VEN 1, including individuals with inhibi- Novo Nordisk: $1.5bn and others, but safety is a key consider- tors to Factor VIII. Roche also is testing the Pfizer: $1.3bn ation for physicians and patients. therapy dosed every other week and ev- Bayer: $1.2bn ery four weeks. CSL Behring: $1bn emophilia patients are loyal to “Patients on standard of care bypass brand-name clotting factors that Bioverativ: $847m therapy are still bleeding quite a bit; there’s have enjoyed market dominance for *Grifols and Octapharma do not report prod- definitely an unmet need,” Roche subsid- H uct-level sales or hemophilia franchise totals, many years, but a shakeup may be coming iary Genentech Inc.’s Gallia Levy, associate but they are major players in the market. in the form of monoclonal antibodies, RNA- group medical director, told Scrip during based treatments and gene therapies if the ASH meeting. safety factors and treatment durability don’t back with [Biogen spinout Bioverativ Inc.’s Levy noted that many hemophilia A get in the way. recombinant Factor IX product] Alprolix.” patients aren’t adhering to treatment Shire PLC has the world’s largest he- Walsh was more optimistic about new regimens, because of the burden of infu- mophilia franchise following its acquisi- biologic approaches, since subcutaneous sions three and four times per week, so tion of Baxalta Inc., generating more than administration every one or two weeks emicizumab’s once-weekly – or even less twice the sales of its nearest competitor would be a big convenience and compli- frequent – injections could be a significant Novo Nordisk AS. Those companies’ mar- ance benefit compared with weekly or differentiating factor in the market. ket dominance will be challenged, how- more frequent clotting factor infusions. However, a recently reported patient ever, by novel therapies from the likes The doctor was less enthusiastic about death in HAVEN 1 raised new questions of Roche, Alnylam Pharmaceuticals Inc. gene therapies, however, based on the about which patients are the best candi- and Spark Therapeutics Inc., which could early-stage data presented to date. dates for treatment with emicizumab and eliminate the need for frequent clotting Shire’s group vice president and head of how they should be treated when they ex- factor infusions. US hematology Jeffrey Schaffnit said in an perience a breakthrough bleeding event. However, hemophilia patients tend to interview with Scrip during the American Shire contends that emicizumab may be reluctant to give up therapies that have Society of Hematology (ASH) Annual Meet- not be safe enough for patients that re- been safe and effective for many years, ing in December that the safety of new quire frequent and life-long therapy. The which could mean slow acceptance and therapies is key for hemophilia patients, company generated in vitro data last year growth for newer products. who’ve relied on products like Shire’s anti- for Feiba dosed concomitantly with an Physicians and patients are interested in inhibitor activated prothrombin coagulant emicizumab biosimilar, which showed that new therapeutic approaches, but they are complex Feiba for decades. thrombin levels jumped four to 10 times reluctant to switch from approved clotting “We fully support the innovation of these above pre-treatment levels, increasing the factors, according to a Feb. 28 report from products, but they shouldn’t have any ad- risk for serious adverse events. The preclini- Bernstein analysts Ronny Gal and Tim An- ditive risks,” Schaffnit said. “We think further cal findings were published in the journal derson based on an interview with hemo- study is warranted.” Blood just before the ASH meeting. philia key opinion leader (KOL) Christopher A Suntrust Robinson Humphrey analysis Walsh, a Mt. Sinai Hospital hematologist EMICIZUMAB QUESTIONS of the in vitro data on Dec. 2 noted that and an associate professor at the Icahn The most advanced of the new treatment thromboembolic events and thrombotic School of Medicine at Mt. Sinai. modalities is Roche’s monoclonal antibody microangiopathy (TMA) – the serious ad- “Within the [Factor VIII (FVIII)] market, Dr. emicizumab (ACE910), which was given verse events reported in HAVEN 1 – appear Walsh sees little traction from the longer- prophylactically in the Phase III HAVEN to be a result of co-administration of emi- acting FVIII products and sees many of his 1trial to patients with hemophilia A, in- cizumab with a bypassing agent, because patients switching back to the older prod- cluding individuals who have developed the severe side effects are not known to ucts as they do not feel ‘protected.’ Discus- antibodies – also known as inhibitors – to occur among hemophilia patients treated sions with peers suggest at least some clotting factors. The bispecific monoclonal with Feiba or Novo Nordisk’s NovoSeven other physicians have noted the same,” antibody mimics the production of clot- and they occurred only in patients who the Bernstein report says. “Within the FIX ting Factor VIII to bring together Factors IXa had a breakthrough bleeding event in the market, Dr. Walsh is seeing similar switch and X to help the blood coagulate. Roche study.

8 | Scrip intelligence | 24 March 2017 © Informa UK Ltd 2017 EXPERT VIEW

Bernstein noted in its KOL report that Mt. NovoSeven has been on the market since are looking at health care utilization costs Sinai’s Walsh expects broad adoption of 1996 and, like FEIBA, treats patients with as will the forthcoming Phase III program, emicizumab for hemophilia patients with inhibitors. Novo also has long-acting clot- since infusion costs are a big expense for inhibitors if the final data expected later ting factors in late-stage development and payers in terms of reimbursing current he- this year show an 80% or greater reduction under regulatory review as well as a Phase mophilia therapies. in bleeding events versus 50% to 60% re- I monoclonal antibody called concizumab. “The inhibitor population has a high un- ductions for existing clotting factors. If so, However, the company is looking for ways met need and some require treatment that physicians are likely to use the monoclonal to diversify its revenue beyond diabetes cost $1m-plus per year,” he noted. “It’s very antibody in the inhibitor population even and hemophilia and may expand in hema- expensive, so if you can obviate the need without a deeper understanding of the tology, since it is rumored to be considering for bypassing agents – which have a high safety risks. an acquisition of the sickle cell drug devel- burden, cost and risk – you can benefit pa- But for broader used in hemophilia A and oper Global Blood Therapeutics Inc. tients and society.” B, the risks associated with the combination Garg also pointed out the potential qual- of emicizumab and Feiba – and potentially FITUSIRAN NEARING PHASE III ity of life improvement for hemophilia pa- with NovoSeven – would have to be bet- Another closely-watched novel hemo- tients, many of whom avoid sports or other ter understood, the Bernstein report notes. philia treatment in clinical development activities and plan their lives around when That suggests that it could take a while for is the RNA interference (RNAi) therapeutic they are due to get their next clotting fac- emicizumab to have an impact on Shire’s fitusiran from Alnylam and partner Sanofi/ tor infusion. portfolio beyond Feiba if the product is ap- Genzyme Corp. The companies are co- “Factor doesn’t have a consistent effect proved in the US in the next year or so. developing and will co-commercialize the over time,” he said. “We have a clear and drug in the US, Canada and Western Europe, consistent effect; it’s freeing for patients. while Sanofi has rights to fitusiran in the rest Seeing the bleeding rates we’re seeing is of the world. really quite positive and encouraging.” The drug is designed to reduce anti- Both fitusiran and emicizumab are com- thrombin (AT), thereby increasing throm- pelling for payers, which are looking for cost bin, which should improve clotting in savings from new subcutaneous therapies, people with all types of hemophilia, in- which could prevent bleeds without fre- cluding patients with inhibitors, and other quent and costly infusions of clotting fac- bleeding disorders. It is being tested in a tors. The novel medicines also don’t cause four-part Phase I/II study ahead of Phase III patients to develop inhibitors, which leads studies that are expected to begin during to treatment with more expensive bypass- Shutterstock: Jarun Ontakrai Jarun Shutterstock: the first half of this year. ing agents, like Feiba and NovoSeven. Alnylam presented interim Phase I data Gene therapies are not as compelling Shire certainly has a lot at stake with for fitusiran at ASH that showed reduced in the eyes of payers, however, because around a 50% share of the hemophilia levels of AT, increased thrombin and a me- they have not yet determined how to pay market after closing its acquisition of Bax- dian annualized bleeding rate (ABR) of zero for what could be once-in-a-lifetime treat- alta last year, making hemophilia the com- in 16 patients with hemophilia A or B with ments, according to a recent report from pany’s largest franchise. Baxalta’s hematol- inhibitors who were treated with a once- Datamonitor Healthcare. ogy franchise generated $3.7bn in 2016 monthly subcutaneous injection of fitu- sales, which was 3% more than in 2015 on siran versus a pre-study median ABR of 31. GENE THERAPY CLAMOR a non-GAAP basis, but Shire recognized The median ABR in the company’s Phase II Six gene therapies and a gene-editing treat- only $2.2bn in post-acquisition hemophilia extension study was 1 as of the data cutoff ment for hemophilia are in Phase I/II test- sales, or 20.6% of the company’s $10.7bn in for the ASH presentations. ing, although BioMarin Pharmaceutical Inc. product sales last year. All side effects in the Phase I study were plans to move its BMN 270 for hemophilia Novo Nordisk reported DKK10.5bn characterized as mild or moderate with A into a potentially registrational Phase IIb ($1.5bn) in hemophilia sales for 2016, no thromboembolic events reported, in- clinical trial in the third quarter of 2017, and which accounted for 9.4% of the Danish cluding among patients who experienced uniQure NV intends to begin a pivotal trial company’s DKK111.8bn ($15.9bn) in prod- breakthrough bleeds that were managed for its hemophilia B candidate AMT-060 later uct sales. Novo said in its annual report that with bypassing agents – recombinant Fac- this year as well. its hemophilia sales declined by 2% from tor VIIa and/or activated prothrombin com- Spark and Dimension Therapeutics Inc. 2015 levels, because of “lower NovoSeven plex concentrate (Shire’s Feiba and Novo continue to report data from ongoing sales in the USA due to increased compe- Nordisk’s NovoSeven). Phase I/II clinical trials for their hemophilia tition and patients participating in clinical “Patients are very excited about some- gene therapies, but Sangamo BioSciences trials with competing drugs, partly offset thing with such a different approach,” Al- Inc. only recently started trials for its hemo- by the roll-out of NovoEight in Europe and nylam chief medical officer Pushkal Garg philia A gene therapy SB-525 and its hemo- the USA, and by sales growth for NovoS- said in an interview with Scrip during ASH. philia B gene-editing therapy SB-FIX and even in [Asia] Pacific.” Garg said the ongoing early-stage studies CONTINUED ON PAGE 10 scrip.pharmamedtechbi.com 24 March 2017 | Scrip intelligence | 9 EXPERT VIEW

CONTINUED FROM PAGE 9 tific Symposium Apr. 6 to 8 in Scottsdale, little value in AMT-060 given 1) competi- expects its first data from those studies in Arizona. Discussions with the FDA are on- tion, 2) small market size and 3) adequacy late 2017 or early 2018. Spark and uniQure going about the design of a Phase III study, of existing therapeutics. Given the com- reported interim results during the ASH which would be run by Pfizer. petition from SPK-9001 and availability of conference in December. Spark and its Spark’s wholly-owned hemophilia A long-acting recombinant FIX replacement partner Pfizer Inc. presented data from gene therapy SPK-8011, which delivers therapeutics (yielding about 20% FIX ex- seven out of nine adult patients with he- Factor VIII, is about a year behind SPK- pression with weekly prophylactic dosing), mophilia B who were at least 12 weeks past 9001, so the first set of data from an on- we see little commercial opportunity for infusion with the gene therapy SPK-9001 as going Phase I/II study are expected in AMT-060.” of the Nov. 30 data cutoff. Those individuals mid-2017. Even so, Yang said uniQure has about were able to produce Factor IX (FIX) at suf- “We continue to see a reasonable a 75% chance of winning FDA approval ficient levels after a single infusion. chance to show clinically meaningful im- for AMT-060 based on available data. Baseline FIX levels were less than 2% of provement in [the] initial cohort … based She forecast cumulative sales of $785m normal, but increased to a range of 12% to on preclinical data,” Leerink analyst Gena between 2020 and 2032 – an average 46% of normal with a mean steady-state Wang said in regard to SPK-8011 in a Feb. of $60.4m per year – based on the gene level of 28%; that’s more than twice the 22 report on Spark’s pipeline. therapy’s potential to penetrate a market 12% level deemed sufficient to prevent of about 7,000 hemophilia B patients in minor, chronic bleeding in the joints – a UNIQURE GENE THERAPY the US and EU. common cause of disability in hemophilia. UniQure will report additional data from “Dr. Walsh believes gene therapy works “Most people are not going to bleed at its Phase I/II study for AMT-060 for hemo- in principle, but its adoption is gated by that level,” Spark co-founder, president and philia B in 2017 as it prepares to initiate high variability of results,” the Bernstein chief scientific officer Katherine High said a pivotal study this year, but at the ASH KOL report said. “He expects gradual in an interview at ASH. meeting the company presented results adoption as the technology gets better, Six patients reported increased physical from ongoing earlier-stage study for pa- but this would require multiple genera- activity and improved quality of life, be- tients in the low-dose cohort treated for tions of products (it would not be first- cause they did not have to continue with up to 52 weeks and in the higher-dose to-market wins).” once- or twice-weekly clotting factor infu- cohort for up to 31 weeks. Three patients That may be good news for Shire after sions. Patients have indicated that the ben- across both cohorts were given tapering all, since the company has gene therapies efit for gene therapy is “the freedom from doses of corticosteroids to treat mild in- in preclinical development for hemophilia worrying about when you’re going to bleed creases in liver enzymes. A and B – SHP654 for hemophilia A and and when was your last infusion,” High said. Four out of five patients in the second SHP648 in hemophilia B, which were ac- “The goal of all drug development is to cohort required chronic FIX infusions prior quired by Baxter International Inc. before give patients choice in how they manage to the clinical trial (the fifth had less se- it spun out Baxalta as a separate company. their disease,” she added. “Patients find this vere disease and used FIX therapy only as Both assets were initially developed by life-changing.” on-demand treatment) and were able to Chatham Therapeutics LLC. However, Spark reported that two pa- discontinue prophylactic FIX therapy after “The biggest thing to overcome [in gene tients had elevated liver enzymes associ- receiving AMT-060. Only one spontaneous therapy] is the immune response … but ated with an immune response to the viral bleed was reported at the data cutoff after there’s a lot of technology looking at what vector capsid that’s used to deliver FIX DNA the hemophilia B patients stopped pro- can be done to minimize that, looking at to the liver. They were treated with taper- phylactic FIX therapy. new capsids and vectors. It’s as close as it’s ing courses of corticosteroids and their All five patients in the first cohort had ever been in terms of commercialization,” FIX levels dropped, but the two patients uncontrolled bleeding episodes despite Schaffnit said. did not have any breakthrough bleeding prophylactic FIX therapy prior to treatment “We want to maintain our leadership; events or require FIX infusions. with AMT-060. They maintained “robust, we’re looking to expand our breadth,” he added, noting Shire’s investments in gene High said the immune response seems constant and clinically meaningful levels therapies, treatments for ultra-rare disor- to occur between four and eight weeks of FIX activity” for up to 52 weeks, accord- ders, like Von Willebrand disease, and the after infusion with SPK-9001, so Spark will ing to uniQure, with a mean FIX expression company’s Phase I long-acting recombi- look for signs of an immune response dur- level of 5.2%. nant Factor VIII candidate SHP656, which ing that period going forward and treat it None of the 10 hemophilia B patients is being developed with technology from with steroids before FIX levels fall too far. across both cohorts of the study devel- Xenetic Biosciences Inc. No patients treated with SPK-9001 devel- oped inhibitors. The safety and efficacy Published online 15 March 2017 oped FIX inhibitors and none experienced data supported uniQure’s decision to thrombotic events or other series side ef- test the higher dose in its forthcoming CLICK fects. More data from the 10-patient Phase pivotal trial. View Hemophilia I/II study and an update on Phase III plans Jefferies analyst Eun Yang said in a report Pipeline here: are expected around the Hemostasis and issued on Dec. 5 in response to the data http://bit.ly/2mkRGix Thrombosis Research Society (HTRS) Scien- presented at ASH that “we continue to see

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Fortress Adds Rare Disease- Focused Subsidiary Cell Medica Targeting Next CAR-T Wave Fortress Biotech Inc. unveiled a new The next generation of chimeric antigen receptor T-cell (CAR-T) therapies subsidiary March 14, Cyprium Thera- to be developed, where most companies are at around the same (preclini- peutics, Inc. focused on treatments for cal) stage, is expected to be aimed at treating solid tumors, and the Anglo- the rare pediatric genetic disease Men- American biotech, Cell Medica Ltd., believes it will be advancing its first kes disease and related copper metabo- potential products in this sector into clinical studies sometime in 2018. lism disorders. Fortress now has nine Kite Pharma Inc., Novartis AG and others may be nearing the market for companies under its umbrella, a few the treatment of blood cancers with their CD19-targeted CAR-T products, of which are developing drugs for rare but there is a “whole new category of therapies, an unexplored continent,” diseases. Fortress, which finances each out there relating to cell immunotherapies, says Cell Medica’s CEO Gregg subsidiary company separately and Sando. The UK-headquartered biotech has just raised a hefty £60m ($73m) through various means, while retaining in a Series C financing round partly to support development of its lead an economic stake, has a goal of bring- product, a Phase II Epstein-Barr virus-associated anticancer, baltaleucel-T ing in one or two new portfolio com- (CMD-003), but also to support its work on its next generation of cell im- panies quarterly. The firm’s 20-person munotherapies. Since raising £50m at the end of 2014 in a Series B round, business development team is hard at Cell Medica has expanded its chimeric antigen receptor (CAR) technology work scouring the life sciences sector for with two large research collaborations (with Baylor College of Medicine assets, CEO Lindsay Rosenwald said in and with University College London) and the acquisition of Delenex Ther- an interview at the company’s New York apeutics AG. The company will now execute on its plans to develop new City headquarters March 8. Days later, products with the Series C funding, Sando said. Cell Medica’s cell-based Fortress followed through on its com- technologies involve the use of natural killer T-cells that traffic naturally pany-building ambitions by announc- to the periphery of the human body where most solid tumors are located; ing the formation of Cyprium. The new other T-cells, such as those used as the basis of the first generation of T- company will be focused on the develop- cell based immunotherapies, tend to circulate around the blood and lym- ment of the Phase III candidate CUTX- phatic systems, Sando noted. 101 for the treatment of Menkes dis- [email protected], 16 March 2017 ease, a rare pediatric disease caused by genetic mutation of copper transporter ATP7A that affects one in 100,000 new- and commercialize an adeno-associated the US FDA has approved an IND for borns each year. Menkes patients often virus (AAV)-based gene therapy, AAV- a Phase II study of GSP 304 (tiotro- have low levels of copper in their blood ATP7A, to deliver copies of the copper pium bromide) for the treatment of and brain, and clinical features of the transporter that is defective in Men- chronic obstructive pulmonary dis- disease include connective tissue disor- kes patient and be used in combination ease (COPD). The added-value generic ders and severe neurological symptoms with CUTX-101. The gene therapy is in is being developed as a maintenance such as seizures. Many patients die be- preclinical development at NICHD. therapy for bronchospasm associated fore the age of three. Milder versions [email protected], 15 March 2017 with COPD, administered once-daily of ATP7A mutations are associated using an oral nebulizer. Mumbai- with other diseases, including Occipi- based Glenmark characterized the tal Horn syndrome and ATP7A-related Glenmark Wins ‘Milestone’ FDA nod as a “milestone” in its drive distal motor neuropathy. There are no US Nod For COPD to be a more innovation-focused com- FDA-approved treatments for Menkes pany. “Moving GSP 304 into Phase II disease and its variants, according to In the face of increasingly cut throat is a great example of that focus and, Fortress. CUTX-101 is a subcutaneous generic competition, Glenmark Phar- if approved, will be the first nebulized injectable formulation of copper his- maceuticals Ltd. is betting on its spe- form of tiotropium bromide,” noted tidinate. Cyprium will develop the drug cialty and innovative drugs pipeline, Fred Grossman, president and chief under a Cooperative Research and De- and the development of niche and medical officer of Glenmark Pharma- velopment Agreement (CRADA) with complex generics and new dosage ceuticals Inc. in the US. Currently, tio- the Eunice Kennedy Shriver National forms, to power future sales in a strat- tropium bromide is marketed in the Institute of Child Health and Human egy focusing on three therapeutic ar- US by Boehringer Ingelheim GMBH Development (NICHD), part of the eas – respiratory, oncology and derma- in powder form under the brand name National Institutes of Health. Cyprium tology. Now, in what the Indian firm Spiriva and as a spray under the Spiri- and NICHD have also entered into an sees as an important development for va Respimat label. exclusive license agreement to develop its respiratory and broader ambitions, Penelope MacRae,16 March 2017 scrip.pharmamedtechbi.com 24 March 2017 | Scrip intelligence | 11 RESEARCH & DEVELOPMENT

AstraZeneca’s Lynparza Looks To Hang On To Lead Tesaro’s niraparib has an advantage over other PARP inhibitors in that it has been tested successfully in ovarian cancer patients with and without BRCA mutations, but AstraZeneca thinks it may have a case for broad labeling in this population. EMILY HAYES [email protected]

straZeneca PLC’s strong results for (gBRCA)-mutated advanced ovarian cancer AstraZeneca initially sought accelerated Lynparza in maintenance treatment after three or more prior lines of therapy. approval in the US for Lynparza as a main- Aof ovarian cancer could help the SOLO-2 will serve as a confirmatory trial to tenance therapy based on Study 19, but PARP inhibitor retain its leadership position convert the drug’s accelerated approval to the agency asked the company to go back in the class, particularly if the company per- full approval in the US and the data support and study the drug as a later line therapy suades the US FDA to approve the drug in a maintenance therapy indication. for heavily pretreated patients. Sovak ex- this indication for all comers, regardless of The SOLO-2 study tested a new dosing plained that more is known about the mutation status. regimen – 300 mg twice daily – as a main- PARP class now and suggested that Study Lynparza (olaparib) was the first poly tenance treatment for germline BRCA- 19 may now be viewed in a different light. ADP-ribose polymerase (PARP) inhibitor mutated platinum-sensitive relapsed ovar- Although Study 19 included platinum- to reach the market, in 2014, but Clovis ian cancer. The current approved dose is sensitive ovarian cancer patients regardless Oncology Inc.’s Rubraca (rucaparib) was 400 mg twice daily and the new regimen of BRCA mutation status, the current data approved in December 2016 and Tesaro promises to reduce the pill burden from 16 in the overall population doesn’t seem suf- Inc.’s niraparib is under review at FDA with to four tablets daily. ficient for approval in the wider patient a June 30 user fee date. Studies on all three AstraZeneca reported a statistically sig- subset, Datamonitor Healthcare analyst drugs were presented at the Society for Gy- nificant improvement in PFS compared to Zachary McLellan said. necologic Oncology (SGO) Annual Meet- placebo: 19.1 months versus 5.5 months In a five-year follow-up for Study 19 ing on Women’s Cancer from March 12-15 – a 70% improvement, per investigator re- published last year, median survival for in National Harbor, Maryland. view. It also reported significant improve- patients treated with Lynparza was longer AstraZeneca presented impressive data ments on a range of secondary endpoints, compared to placebo – by 4.7 months in for Lynparza in the SOLO-2 study, which including a 50% reduction in time to sec- gBRCA-mutation-positive patients and two tested the drug against placebo as a main- ond progression or death. Safety was in months in the overall trial population – but tenance treatment for patients with BRCA line with prior trial results. the overall survival results were not statisti- mutations, after two lines of therapy, on Biomedtracker analyst David Dahan cally significant, the analyst observed. March 14 at the SGO meeting. This followed said the results were impressive. Cross-trial “Additionally, any survival increase in the a top-line release from the trial in October. comparisons suggest it is equal to nirapa- overall trial population is likely driven by the Tesaro has been hoping to reach the rib in gBRCA patients with a better safety gBRCAm+ cohort. AstraZeneca announced market with niraparib as the first PARP in- profile; for example, lower rates of Grade 3 further analysis into the patients without hibitor approved to treat women regard- or higher thrombocytopenia, neutropenia BRCA mutations who were positive for oth- less of mutation status and as a mainte- and anemia. er homologous recombination deficiencies nance therapy. “Niraparib, however, has the advantage is ongoing. That data would likely need to Niraparib is under review at FDA as a once- of having demonstrated efficacy in pa- be significant and be included in any regu- daily maintenance treatment for patients tients who had tumors with homologous latory submission for Lynparza’s approval with platinum-sensitive, recurrent epithelial recombination deficiency (HRD) as well as beyond BRCAm+ patients,” McLellan said. ovarian, fallopian tube or primary peritoneal in non-gBRCA patients, which may trans- cancer who have responded to platinum- late to a wider label,” he noted. NIRAPARIB’S SECONDARY GOALS based chemotherapy, supported by pro- AstraZeneca will discuss the data with Activity in the market suggests investors gression-free survival (PFS) data from the the FDA in pursuit of expanded labeling think AstraZeneca’s gain is Tesaro’s loss. Tes- Phase III ENGOT-OV16/NOVA study. Positive beyond fourth-line treatment. While SOLO- aro stock fell 10.6% on March 14 to $153.65 secondary endpoint data from the trial were 2 enrolled patients with BRCA mutations, per share. presented at the SGO meeting on March 13. Lynparza was tested in a broader popu- Yet Tesaro presented additional positive The Tesaro drug’s advantage might be a lation in the Phase II Study 19, a mainte- data for niraparib in the NOVA study at the short-lived, however, if AstraZeneca can le- nance trial. AstraZeneca believes the drug SGO meeting that support the drug’s ap- verage its latest Lynparza data for a broader has prospects for approval in all comers, proval as a maintenance therapy in recur- approval. regardless of mutation status, based on rent ovarian cancer, ahead of the drug’s AstraZeneca presented new data from the totality of the data, though it needs to user fee date on June 30. No FDA advisory SOLO-2 study that promise to expand the discuss this with regulators, Mika Sovak, ex- committee is needed for the review and role of Lynparza, which is cleared in the US ecutive director and Lynparza global devel- Tesaro has advised it expects rapid approv- for use as a monotherapy for germline BRCA opment lead, told Scrip. al and plans to launch in the first half.

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In the study, the chemotherapy-free inter- in both germline BRCA-mutated patients who had one prior therapy and 52% who val was significantly improved for patients and patients without these mutations. This had three or more prior treatments. Credit who were BRCA-mutation positive as well bodes well for niraparib’s regulatory sub- Suisse analyst Kennen MacKay said in a as those without germline BRCA mutations missions as a maintenance regimen for re- March 13 note that the ORR data for Rub- compared to the placebo control arm – the current platinum-sensitive ovarian cancer raca in pretreated patients with germline hazard ratios were 0.26 and 0.50 respectively. patients regardless of mutation status,” the BRCA mutations looked competitive with The time to first subsequent treatment analyst commented. Lynparza. PFS and duration of treatment was significantly improved for those with data favored Rubraca, though the data and without BRCA mutations. Tesaro also CLOVIS’S COMPETITIVE ORR DATA for Lynparza reflected patients who had reported a 52% improvement in time to Clovis Oncology Inc. reported additional more prior therapy, the analyst noted. second progression for those with muta- subgroup results for BRCA-mutated pa- There were no new safety signals in the tions and a 31% improvement in those tients taking Rubraca in the Phase II ARIEL2 data at the SGO meeting. without mutations, plus a trend toward im- study of 493 patients with relapsed plat- McLellan noted that the ARIEL2 trial data proved overall survival. inum-sensitive ovarian cancer at the SGO were positive for Clovis, but only pertain to The company had reported in Decem- meeting. Rubraca is a relative newcomer patients with BRCA mutations. ber 2016 that the drug met the primary on the market, having been approved in “Efficacy beyond BRCA-mutated cancers endpoint of the trial, with significantly December 2016 for patients with BRCA will be important as more PARP inhibitors increased PFS in patients with germline mutation (germline and/or somatic) asso- reach the market and companies attempt BRCA mutations (73%) or without (55%) ciated advanced ovarian cancer, after treat- to differentiate their respective therapies versus control. ment with two or more chemotherapies. and increase available patient populations,” Combined with previously released PFS “These data demonstrate that the objec- McLellan said. data from the NOVA trial, the evidence re- tive response rate (ORR), disease control Rubraca is in Phase III for use as a main- affirms that niraparib could become the rate (DCR) and median progression-free tenance treatment in ovarian cancer and leading PARP inhibitor in treating ovarian survival (PFS) in patients with a BRCA mu- data are expected in the middle of this cancer, McLellan said. tation were greatest in platinum-sensitive year. The study is enrolling patients with “The Tesaro update at SGO showed ni- patients,” Clovis said in a statement. and without BRCA mutations, but the pri- raparib treatment significantly improved Among the platinum-sensitive patients mary endpoint is progression-free survival the chemotherapy-free interval and time enrolled in the trial, the objective response in molecularly defined subgroups. to first subsequent treatment over placebo rate (ORR) was 70% overall, 83% in those Published online 14 March 2017

Editas Deal Opens Allergan’s Eyes To CRISPR LUCIE ELLIS [email protected]

Editas’ stock shot up 11% by mid-morn- approved products. Allergan can license via a single adeno-associated virus (AAV) in- ing on March 14, after the gene therapy anything Editas develops over the next jected into the eye. The company has not dis- company announced a deal with Aller- seven years in the ophthalmic space, but closed which vector it is using as the AAV, but gan worth $90m up front for “cool” CRIS- has already expressed interest in three has said it is one that has been administered PR programs in ocular indications. How- programs, including the LCA candidate, to the human eye before. ever, the lead therapy included in the deal one targeting usher syndrome – a form Raffat also noted, however, that Editas’ offers potentially limited profitability in a of retinitis pigmentosa – and another for CRISPR programs are yet to be tested in hu- small orphan space. ocular disease manifestations of herpes mans and that the LCA10 population being simplex virus (HSV). targeted by the company represents a small llergan PLC has entered a strategic Evercore ISI senior analyst Umer Raffat market. He estimates the cumulative market alliance with Editas Medicine Inc. for described Editas’s CRISPR platform as “cool for the LCA10 gene-editing therapy to be Aexclusive access and the option to li- technology” and said in a March 14 research worth $1.6bn, amortized over several years. cense up to five of the latter firm’s genome- note that the lead LCA program is a “super Unusually, Europe is expected to be the more editing ophthalmic programs – including its orphan indication” for Allergan. The LCA pro- valuable market for this treatment, as the esti- lead program for Leber congenital amauro- gram involves editing of the CEP290 gene, a mated prevalence of the condition is approx- sis (LCA), a rare, inherited retinal degenera- protein that plays an important role in cen- imately 1,700 cases compared to only 300 in tive disease that appears in childhood and trosome and cilia development. Mutations the US. Published online 14 March 2017 leads to blindness. This lead therapy is due in CEP290 can cause the frequent form of to enter Phase I trials later in 2017. LCA called LCA10. CLICK Editas will receive a $90m upfront fee Editas’s therapy uses Cas9 endonuclease Read full story at: from Allergan as well as potential mile- to remove the mutation, repairing the gene, http://bit.ly/2mkYsF3 stone payments and royalties from any with all components of the process delivered scrip.pharmamedtechbi.com 24 March 2017 | Scrip intelligence | 13 INFOGRAPHIC

The Industry’s E orts In Targeting The Microbiome. THE MICROBIOME Why It Is Important 100 trillion $4.8 billion The number of bacteria, fungi, protozoa Estimated annual US acute care and viruses residing in or on our bodies, costs of C. dicile infection, one known collectively as the microbiome. Changing the composition of microbiome-related disorder. the microbiome, or the way it interacts with the human body, Some roles of the microbiome: could have therapeutic e ects Digesting food in in ammatory bowel disorders, >30 Producing vitamins Clostridia-associated diarrhea, New biotech companies are Regulating the immune system. diabetes and obesity. focused on developing drugs to modify the microbiome. The number of mentions of the microbiome in Scrip Intelligence has been rapidly Just under $1 bn in public increasing since 2011. and private funding has been invested since 2011 to support companies that are researching 6 8 13 17 24 54 therapeutic approaches targeting 2011 2012 2013 2014 2015 2016 the microbiome.

RESEARCH ACTIVITY IN THE MICROBIOME AREA BY STAGE OF DEVELOPMENT DISCOVERY PRECLINICAL Enterome/J&J/EB110 Allergan/Assembly Biosciences/ABI-M201 Synlogic/SYNB1020 Crohn’s disease ulcerative colitis urea cycle disorders Enterome/Takeda/EB420 Allergan/Assembly Biosciences Inc./ABI-M301 Synlogic/SYNB2010 ulcerative colitis, irritable bowel disease Crohn’s disease phenylketonuria Da Volterra/DAV121 Vedanta Biosciences/J&J/VE202 C dicile-associated diarrhea in ammatory bowel disease Seres Therapeutics/SER-301 C3J Therapeutics/CD17-DL ulcerative colitis C dicile infection Synthetic Biologics Inc/SYN-020 Symbiotic Health/SHP-01 GI disorders C dicile infection DISCOVERY PRECLINICAL PHASE I PHASE II PHASE IIB 2 10 5 3 3

PHASE I PHASE II PHASE IIB Seres Therapeutics Inc./SER-262 Seres Therapeutics Inc./SER-109 Rebiotix Inc./RBX2660 C dicile-associated diarrhea C dicile-associated diarrhea C dicile-associated diarrhea Seres Therapeutics Inc./SER-287 Shire/VP20621 Summit Therapeutics PLC/ridinilazole ulcerative colitis C dicile-associated diarrhea C dicile infection Second Genome Inc./SGM-1019 C3J Therapeutic/C16G2 Synthetic Biologics/SYN-004 (ribaxamase) Crohn’s disease dental caries prevention Microbiome disruption by antibiotics Enterome Bioscience SA/EB88018 DAV132/Da Volterra Crohn’s disease C dicile infection Data supplied by Microbiome Therapeutics/NM-505 Synthetic Biologics/SYN-010 (metformin, prebiotic bers) constipation associated with diabetes type 2 irritable bowel disease

14 | Scrip intelligence | 24 March 2017 © Informa UK Ltd 2017 PRICING

NICE Appraisal Changes: A New Pricing Hurdle LUCIE ELLIS [email protected]

New NICE and NHS England appraisal is not a long-term solution and has raised Adela Williams, partner at law firm Ar- rules regarding timelines and price concerns that companies will face pressure nold & Porter Kaye Scholer, told Scrip this thresholds – labeled stark and contradic- to maintain the reduced price after that was an irrational move by NICE and NHS tory – could fast-track new cost-effective phase-in time has expired. England. “If you have a medicine that is drugs but then subject the same products If a company decides to hold out, and so cost effective it has a price of less that to significant delays of multiple years. by the time the extension period ends no £10,000 per QALY, then simply because commercial agreement has confirmed, there is a large population eligible for it ew rules set to come into force next then NHS England must provide the prod- you shouldn’t be able to defer implemen- month that will allow NHS England uct to patients at the price originally agreed tation,” she said. Nto press the pause button on the by NICE. However, this could be as much as use of around 20% of new drugs, even af- three years later, delaying both access to MULTIPLE COST ASSESSMENTS ter they have been deemed cost effective the medicine for patients and revenues to “These proposals emasculate NICE to some by NICE (National Institute for Health and the company significantly. extent and represent a shift in power to- Clinical Excellence), look set to heap further NICE, which first announced potential wards NHS England that wants to carry pricing pressure on companies hoping to changes to assessment timelines and pric- out its own determinations for prioritizing access the major UK market. ing caps in October 2016, will reassess the treatments,” said Williams, who specializes Currently once NICE, which is respon- new rules in three years’ time to see what in advising companies on UK reimburse- sible for deciding whether new drugs impact it has had on access to new drugs. ment systemts. show enough benefit versus their cost Last year £16.8bn was spent on drugs by the Rare disease drug developer Alexion, for use on the National Health Service, NHS, only a small segment of the healthcare which has experienced arguing for access to has granted a recommendation, NHS provider’s total budget for 2016 of £102bn. the NHS for its highly specialized drugs, told England must provide the product to Sir Andrew Dillon, chief executive of Scrip that these changes to the system were patients within 90 days. However, under NICE, said the changes would “enhance a “serious setback for patients in England suf- new rules agreed on March 15 and which our ability to optimize access to innovative fering from rare and ultra-rare diseases, and will be put into action within weeks, NHS treatments in the light of the significant -fi for the life-sciences industry in England.” The England will be able to play for more nancial challenge facing the NHS.” company said it called into question wheth- time before providing the drugs, delay- er England remains a viable country in which ing their use despite their being consid- FAST-TRACK PLANS to invest and launch new therapies. ered cost effective. In parallel to the introduction of a budget “Alexion questions the government’s Instead of 90 days, NHS England will impact test, NICE will next month introduce commitment to its patients and its be able to request up to 1,096 days (a a scheme for fast-tracking new drugs that pledge to support the life-sciences in- maximum three years) to try to negoti- have a likely cost per extra year of quality- dustry,” a spokesperson for the company ate a new price with manufacturers of adjusted life (QALY) of under £10,000. New said. “This decision also puts the UK’s In- drugs that are expected to cost more that drugs that come in under this threshold dustrial Strategy at risk, which highlight- £20m a year to the NHS – a method NICE will be considered “exceptional value for ed the life sciences sector as a primary is calling a “budget impact test.” It is an- money,” the committee noted. Under the source of innovation for the UK economy ticipated that this cost cap will affect one fast-track option, NHS England would be going forward.” in five new drugs in England. Previously, required to offer the new medicine to pa- Industry body the ABPI added that the assessments for novel therapeutics were tients within 30 days instead of the tradi- new plans would “prevent patients from only assessed on cost versus benefit for tional 90-day deadline. receiving NICE approved, cost-effective individual patients – not by the total cost This is a positive new guidance that medicines, undermining their basic rights it may incur to the NHS. could speed up market access in England under the NHS constitution.” The £20m budget impact assessment is for drug developers of products with lower Industry has raised concerns over how being seen as a second pricing hurdle for per-patient costs. the £20m threshold has been calculated by companies looking to get drugs to market However, in a contradictory move, NICE and NHS England. After consultation, in England and it also represents a shift in fast-tracked drugs will also be submitted this query remains unanswered. power from NICE to NHS England when it to the new budget impact ruling. Mean- Published online 16 March 2017 comes to drug pricing decisions. During an ing a product could be granted fast-track extended valuation period, in which time status by NICE only to be held up by NHS NHS England will invite drug developers England if the product is likely to create a Why £20m? to negotiate on pricing for products, NICE cumulative bill of more than £20m to the Read more here: will offer phased funding of recommended NHS per year due to the number of pa- http://bit.ly/2nKeqW0 treatments to patients in England – but this tients to be treated.

scrip.pharmamedtechbi.com 24 March 2017 | Scrip intelligence | 15 BUSINESS BULLETIN

Celltrion Healthcare’s Biosimilar Successes Circassia Builds US Respiratory Presence For investors in Celltrion Healthcare, with AstraZeneca Deal the long wait seems to have been worth it. After originally planning an initial Shares in UK biotech firm Circassia Pharmaceuticals PLC jumped by public offering a few years ago, Cell- as much as 30% to 114 pence on the LSE on Mar. 17 on news that it trion Healthcare, the exclusive market- had entered into a deal with AstraZeneca PLC to secure certain US com- mercial rights to two chronic obstructive pulmonary disease products ing, distribution and partnering arm (COPD), Tudorza (aclidinium bromide) and Duaklir (aclidinium bromide of South Korea’s Celltrion Inc., has plus formoterol), for up $230m. Circassia said the deal would “transform picked the perfect timing to launch an its product portfolio and commercial presence”. It already markets the IPO amid the glow surrounding its par- airway inflammation testNiox for use in asthma management in the US, ent from a series of biosimilar approv- EU, Japan and China, and this will immediately provide it with another als in the US and Europe. Earlier this marketed product, as well as giving it another in the wings. In addition to week, Celltrion Healthcare received the the strategic fit with Circassia’s renewed focus on respiratory medicines, green light from the Korea Exchange the deal would leverage Circassia’s commercial infrastructure – it plans (KRX) to launch a float on the second- to double its US sales force as a priority – and put it in a better position tier Kosdaq market, where Celltrion for future production licensing and acquisitions. CEO Steve Harris said is already traded. The IPO, estimated the way the deal is structured was “highly attractive” as it allows Circas- to be worth KRW819.3bn ($714.9m) sia “to fund the consideration without further investment anticipated to KRW1.01tn, is set to be one of the from shareholders, while at the same time welcoming AstraZeneca to our largest ever on the Kosdaq bourse. Al- share register”. The company has been concentrating on its respiratory though details of the IPO will be deter- franchise all the more since its cat allergy product Cat-SPIRE failed in a mined later, Celltrion Healthcare plans high-profile Phase III study last June, wiping more than 60% off its share to price at KRW33,300 to KRW41,000 price. This was Circassia’s lead development drug product and attention per share, the KRX said in a statement, had been particularly focused on it following a highly successful IPO and and the offering is likely to take place funding round by the company. Just prior to the failure, Circassia shares in April. As of the end of 2015, Cell- had been trading at around 270 pence. trion’s chair Jung-Jin Seo, who is also [email protected], 17 March 2017 chair and CEO of Celltrion Health- care, held the largest (46.47%) stake in Celltrion Healthcare, while JP Morgan Chase’s private investment arm One Group Co. Ltd. and Shanghai Pharma- ma and Shanghai Pharma responded Equity Partners owned a 22.44% stake, ceuticals Holding Co. Ltd. have both by releasing official statements a day and Singapore’s Temasek Holdings’ issued public statements denying the after the reports, with Fosun Pharma Ion Investment a 15.62% holding. Cell- speculation reported. Even so, the two stating that “there is no such plan or trion Healthcare’s IPO filing and ap- Chinese companies are continuing to arrangement as the media reports; the proval come several years after it first seek potential overseas targets as part content of the report does not match unveiled plans in 2015 to launch an of their internationalization strate- the actual situation.” Shanghai Phar- IPO in South Korea or overseas. Under gies. News reports quoting sources ma acknowledged that it has a con- an agreement reached when its overseas with knowledge of the matter emerged tinuous focus on identifying overseas investors made investments in Cell- on March 9 that Fosun Pharma and acquisition opportunities as part of trion Healthcare several years ago, the company had agreed to launch an IPO Shanghai Pharma shared an interest in its internationalization strategy dur- in 2014, but this timing was delayed. bidding for Stada in a possible €3.6bn ing China’s 13th Five-Year Economic [email protected], 16 March 2017 ($3.8bn) takeover battle. Reuters re- Plan. The company has had prelimi- ported that Fosun Pharma was in nary contacts with several pharmaceu- talks with funds including CVC Capi- tical companies in Europe and the US, Fosun/Shanghai Deny tal Partners for a possible joint bid, but no formal statement of intent has while Bloomberg stated that CVC was been made to any including Stada, it Interest In Stada teaming up with Shanghai Pharma to said. Shanghai Pharma stressed that its In response to reports of their interest compete against other investor groups. business operations are continuing as in acquiring Germen generic and over- Both reports noted that the pharma normal and that it has not hidden any the-counter firm Stada Arzneimittel companies may consider making an information required to be disclosed. AG, Shanghai Fosun Pharmaceutical initial offer alone. Both Fosun Phar- [email protected], 14 March 2017

16 | Scrip intelligence | 24 March 2017 © Informa UK Ltd 2017 COMPANY FOCUS

Lilly Eyes Top 10 Japan Ranking Built On Launches IAN HAYDOCK [email protected]

Lilly says it remains on track to enter the around 3% to JPY243.2bn ($2.15bn) in the with drugs launched in 2015 including pharma industry top 10 in Japan by sales calendar year. once-weekly GLP-1 agonist Trulicity (du- by 2020, driven by planned launches of The increase also came despite a roughly laglutide), and SGLT2 inhibitor Jardiance a raft of new products and despite some 5% average price cut for the business in the (empagliflozin), logging good increases major recent losses of exclusivity. April 2016 general biennial reimbursement along with biosimilar insulin glargine, price cut in the country (which averaged which managed to carve out share in the hile there has been recent around 6% across the industry). basal insulin market. speculation from some ob- Reimbursement level sales of Zyprexa, Wservers that a flat overall an atypical antipsychotic, slipped 22% R&D PLANS pharma market outlook and the specter to JPY47.7bn, but Zydis oral-dissolving Head of medicines development unit Dr. of fundamental reimbursement pricing 2.5mg formulations were launched in Toshio Fujimoto stated that the growth reform may negatively affect multina- 2015 for both schizophrenia and bipolar over the next few years will continue to be tionals’ business and R&D commitment disorder to try and provide differentia- driven by Lilly’s global pipeline, noting that to Japan, Eli Lilly & Co. remains strongly tion from the 119 generic presentations fully 90% of the R&D projects in Japan are bullish on its growth prospects in this key launched last year. progressing under global simultaneous de- Asia-Pacific market. Osteoporosis drug Evista (raloxifene) also velopment programs. Country president Patrik Jonsson said suffered from generics, falling by 35% to “Our aim is to get approvals for 20 inno- that the US major still considers Japan - JPY13.1bn. vative products over the 2014-23 period - already home to its largest ex-US single- Even so, “Our sales in Japan have of which five [including Cyramza and Taltz] country business - “by far the number one tripled in 10 years, and we remained have already been launched - in five main priority” outside of its home market. among the top three growth companies target therapeutic areas: oncology, diabe- Alluding to the importance of policy sta- for the eighth consecutive year last year tes, neurodegenerative disorders, autoim- bility, Jonsson told a Tokyo media briefing after Gilead Sciences Inc. and Ono Phar- mune disorders, and pain,” he said. that part of the reason for this confidence maceutical Co. Ltd.,” both of which were In terms of key mid-term products, Fu- is that, along with top-class healthcare and boosted by big-selling individual drugs, jimoto highlighted in particular the oral a reliable social security system, has been Jonsson said. JAK1/2 inhibitor baricitinib (Olumiant), that the “overall environment in Japan has Lilly’s Japan pharma sales ranking as of which has now been filed for rheuma- offered predictability.” December was 12, up from 19 in 2011, but toid arthritis in Japan in line with global Consistent product pricing and the “in- it has released no specific sales targets for timings. novation premium” system that rewards achieving its targeted top 10 position. Other Phase III projects include new indi- innovation by maintaining reimburse- cations for ramucirumab and ixekizumab, ment levels for new drugs during their NEWER PRODUCTS SHINE and abemaciclib for breast and non-small patent life have led to continuous in- The growth in 2016 came mainly from cell lung cancer. vestment, he stressed, implying that this newer major products, with big increases Another area where Lilly Japan says it could be affected if such policies change. for antidepressant Cymbalta (duloxetine; has been innovating is in the customer However, the executive stopped short +37% to JPY41.6bn (including sales by space, specifically its interactions with of wading too deeply into the deepening Shionogi & Co. Ltd.)), helped by new physicians. drug pricing reform debate now getting pain indications, and cancer drug Cyra- Jonsson pointed to a new dedicated underway within the government in Ja- mza (ramucirumab; +314% to JPY28.9bn). website for medical information, and “e- pan, perhaps cognizant that compatriot Cyramza was launched for gastric cancer medical rep” channels that allow the deliv- company Pfizer Japan Inc. was not so reti- and also approved for colorectal and non- ery of scientific and product information to cent in its recent business briefing, when it small cell lung cancer during the year. physicians via video calls with specialized called strongly for wider industry participa- Biologic Taltz (ixekizumab) was also ap- reps, as well as text chats and screen shar- tion in the process. proved in Japan for second-line plaque, ing. Such systems are also being used to pustular, and erythrodermic psoriasis, shorten the time needed to make sched- ZYPREXA IMPACT CONTAINED and psoriatic arthritis - the last indication uled face-to-face appointments. Focusing on commercial performance and ahead of any other country - and Jonsson Lilly now has around 1,900 sales reps in innovation in what was a challenging year said the company is looking to differenti- Japan, among the highest in the industry for Lilly in Japan due to the advent last ate it from competitors by highlighting but a number that Jonsson sees as appro- June of the first local direct generic com- strong clinical results showing potential priate given the launch plans over the next petition for long-time top seller Zyprexa full clearance of disease, an easy to use au- few years. (olanzapine), Jonsson said the subsidiary’s toinjector, and patient support programs. Published online 16 March 2017 overall sales nevertheless increased by The diabetes franchise was also strong, From the editors of PharmAsia News. scrip.pharmamedtechbi.com 24 March 2017 | Scrip intelligence | 17 HEADLINE NEWS

FDA Moves On Endo’s Opana ER Unlikely To Sweep Up Other Opioids Shift toward intravenous abuse with the reformulated long-acting opioid, coupled with reports of a serious bleeding disorder and HIV transmission, spurred an US FDA advisory committee to recommend regulatory action, which could include new labeling, strict risk management measures or market withdrawal.

SUE SUTTER [email protected]

ndo Pharmaceuticals Inc. faces the March 14 note. However, products that use In February 2012, Endo began replac- prospect that the US FDA will request formulations similar to Opana ER may face ing distribution of original Opana ER with Ewithdrawal of, or require new labeling additional scrutiny, he cautioned. the new formulation. In 2013, FDA issued and a restrictive Risk Evaluation and Mitiga- Analysts also do not think FDA’s ultimate a complete response letter to the com- tion Strategy (REMS) for, Opana ER (oxymor- regulatory action will have much of a finan- pany’s supplemental new drug application phone extended-release) due to issues with cial impact on Endo, which has increasingly (sNDA) requesting labeling that describes intravenous abuse. de-emphasized its branded pain portfolio in the product’s abuse-deterrent properties. However, given the unique circumstances favor of other therapeutic areas. The agency also denied Endo’s citizen peti- surrounding the re-evaluation of Opana ER’s In a March 15 note, JMP Securities analysts tion requesting a determination that origi- safety, there is no indication that other long- Donald Ellis and Nazibur Rahman said Opana nal Opana ER had been removed from the acting opioids on the market are necessarily ER accounted for only 4% of their 2017 rev- market for safety reasons. Had FDA granted headed for the same fate. enue estimate for Endo and is not a growth the petition, it would have blocked generics On March 14, 18 of 27 members of the driver. “We do not view this advisory com- of the older formulation. Drug Safety and Risk Management and the mittee as a meaningful event for Endo,” the The FDA concluded there was insuffi- Anesthetic and Analgesic Drug Products ad- analysts said. cient evidence to establish that the original visory committees voted that the benefits of In a press release issued after the two-day formulation had a higher abuse potential the currently marketed version of Opana ER meeting, Endo said it believes that Opana than the reformulated product. The agency do not outweigh the drug’s risks. ER remains an important clinical choice for noted certain data suggested the reformu- Some panelists believed the drug should appropriate patients, and the company “will lation is more easily prepared for injection be removed from the market due to a lack evaluate the range of available options for and the “troubling possibility” that more in- of unique benefit and data suggesting an maintaining access for legitimate use.” travenous use was occurring compared to increased incidence of intravenous abuse “Endo remains confident that the body the original version. since it was reformulated in 2011 with phys- of evidence established through clinical Endo resubmitted the sNDA in January icochemical properties that make it more research demonstrates that Opana ER has 2016 with results from an intranasal abuse difficult to crush, thereby discouraging -in a favorable risk/benefit profile when used study requested by FDA and interim epide- tranasal abuse. as intended in appropriate patients,” said miologic study data on the abuse patterns. However, other committee members, in- Matthew Davis, senior vice president of However, the company withdrew the sup- cluding some who voted that the drug still R&D for Endo’s Branded Pharmaceuticals plement in August in anticipation of more had a positive risk/benefit profile, called for division. “We plan to work collaboratively complete epidemiological data becoming less drastic regulatory action. Their recom- with the FDA as the agency completes its available in late 2016. mendations included new labeling limit- evaluation of Opana ER, while advocating Although Endo said it is not currently seek- ing prescribing to second-line use, warn- to preserve the important benefits of the ing abuse-deterrent labeling claims, FDA ings about the serious risks of intravenous medicine for patients.” nevertheless brought the product to its ad- abuse, and a restrictive REMS limiting who visory committee due to concerns that epi- could prescribe the drug. ABUSE-DETERRENT LABELING demiological data suggest the reformulation Despite the potentially dire circumstances FDA’s safety concerns over Opana ER stem has led to a shift in the preferred pattern of for Opana ER from a regulatory standpoint, from abuse patterns that have evolved abuse from intranasal to intravenous. analysts do not think FDA’s action will have since the product was reformulated several any broad sweeping implications for opi- years ago. DATA ON PATTERNS OF ABUSE oids in general even though the agency still The currently marketed formulation in- At the advisory committee meeting, Endo faces intense political pressure to stem the cludes a polyethylene oxide (PEO) matrix and its experts defended Opana ER’s safety. epidemic of opioid-related overdoses and that is intended to make tablets more dif- Harris Rotman, vice president of US regu- deaths in the US. ficult to crush and abuse by the intranasal latory affairs, asserted that two key events “We don’t see widespread recalls or with- or injection routes. However, FDA’s De- confound the interpretation of epidemiology drawal of opioid products following the cember 2011 approval of the new formu- data on Opana ER abuse patterns: the intro- committees’ discussion this week,” Canaccord lation did not include labeling language duction of an abuse-deterrent formulation of Genuity analyst Dewey Steadman said in a on abuse deterrence. Purdue Pharma LP’s OxyContin (oxycodone

18 | Scrip intelligence | 24 March 2017 © Informa UK Ltd 2017 HEADLINE NEWS

extended-release) in 2010, which led to an nessee, FDA presented data showing that Egalet Corp.’s Arymo ER (morphine sulfate increase in Opana ER abuse, and the launch the state accounts for the highest number extended-release) and Purdue’s Hysingla of generic oxymorphone extended-release of dispensed prescriptions for branded and ER (hydrocodone extended-release). How- products immediately before and after the generic oxymorphone extended-release ever, there have been more than 60 cases introduction of reformulated Opana ER. per 1,000 residents (18.5), followed by of TTP reported with Opana ER, compared Endo pointed to evidence of decreased in- North Carolina (9.9). to just a few with OxyContin. tranasal abuse with the reformulation and as- Puzzled by the high amount of oxy- Advisory committee members generally serted that epidemiologic data suggesting a morphone use and Opana ER intravenous concluded that the epidemiologic data show sharp jump in intravenous abuse of the drug abuse reported in Tennessee, advisory a shift in abuse patterns from intranasal to in Tennessee was an anomaly. committee member Raeford Brown, a pe- intravenous and saw a biologically plausible “Endo believes the totality of the evidence diatric anesthesiologist at the University of pathway between Opana ER’s PEO compo- demonstrates a favorable benefit/risk profile Kentucky, asked Endo whether there is any nent and TTP. When injected, Opana ER has a in the intended population,” Rotman said. difference in the way it markets drugs in dif- short duration of action. It needs to be dosed “Coincident with the introduction of refor- ferent areas of the country. repeatedly and frequently, in a large injection mulated Opana ER, intranasal abuse was “There is not, and actually at the current volume, which could allow for PEO to accu- lower. I.V. abuse initially increased in Tennes- time we’re not prospectively marketing mulate in a person’s body, panelists said. see but has stabilized, and was stable or de- with sales representatives,” Rotman said. “But A 2015 HIV outbreak in rural Indiana likely creasing in other states.” there’s no state-by-state difference.” resulted from the high injection volume and However, Jana McAninch, an FDA medi- the drug’s high price, which make sharing cal officer and epidemiologist, said the data INTRAVENOUS RISKS Opana ER for injection more efficient, there- are compelling that the reformulation has The advisory committee also was pre- by increasing the risk of bloodborne disease caused a shift from intranasal to injection sented with FDA research implicating high transmission, panelists said. route of abuse, although it’s unclear if the molecular weight PEO as a potential cause Advisory committee members acknowl- increase is greater than if the product had of the cases of thrombotic thrombocy- edged that removing Opana ER from the not been reformulated. In addition, limited topenic purpura (TTP), a potentially fatal market likely would shift misuse to other geographic areas, including Tennessee and bleeding disorder, associated with Opana more readily abusable drugs, including the other Appalachian states, appeared to be ER intravenous abuse. generic extended-release and immediate- driving the increases. In addition to high in- PEO is found in other long-acting opi- release forms of oxymorphone. cidence of injection abuse reported in Ten- oid formulations, including OxyContin, Published online 16 March 2017

Scrip Awards Sponsored by Winner 2016

Executive of the Year

Through a year of enormous change for Allergan, Brent Saunders led the company with a decisive and direct vision. Seeing ahead of changing marketplace and environment conditions, his approach was powered by a deep commitment to customers, patients and driving innovation to overcome unmet healthcare needs. Winner: Brent Saunders, president and CEO of Allergan

“Saunders is an outstanding, inspirational leader with a proven track record prior to becoming CEO at Allergan, and (in the period under review) effectively and efficiently bringing two organisations together.” Scrip Awards The Scrip Awards judges Pharma intelligence | informa

scrip.pharmamedtechbi.com 24 March 2017 | Scrip intelligence | 19 POLICY & REGULATION BRIEFS

PTC Gambles On Success With Emflaza Gottlieb Nomination: PTC Therapeutics Inc., already at cross Changes To Generic Approval Process? purposes with the US FDA over its re- filing ofTranslarna (ataluren) for non- President Donald Trump’s choice of Scott Gottlieb to head the US FDA sense-mutation Duchenne muscular could signal efforts to bring reforms among a variety of fronts, perhaps dystrophy (DMD), apparently decided none more notable than how the agency approves generic drugs. Gott- lieb, returning for what would be his third stint at the agency, has been to take a chance on the drug-pricing a staunch proponent for flexible approval pathways, and despite some controversy as well, paying $140m up ominous tweets, the Trump Administration has made speeding ANDA front on March 16 to acquire all rights clearance (rather than direct government intervention) the central focus for Marathon Pharmaceuticals LLC’s of its drug pricing policy efforts. The president’s selection of Gottlieb un- DMD drug Emflaza (deflazacort), the derscores that point, but the effort could require a considerable shift by launch of which has been delayed by FDA to make a politically meaning impact on drug prices. Gottlieb wrote pricing pushback. PTC execs said during in an August 2016 Wall Street Journal op-ed that a series of “costly require- a same-day investor call to outline the ments” imposed by the FDA under the Obama administration are respon- transaction and report fourth quarter sible for keeping generic competitors off the market, and recommended earnings that the company plans to re- that FDA “prioritize applications for generic categories where competi- vise Marathon’s initial Emflaza pricing tors are exiting.” In testimony before a Senate pricing hearing in October, of $89,000 per year, but they offered few Gottlieb also suggested that companies who pursue applications for these specifics. Marathon attracted significant abandoned generics receive a voucher, which would provide the sponsor unwanted attention from Congress and with an expedited review of another generic application. “The value of this the media with its planned pricing of voucher would give firms more incentive to market copies of low-volume the DMD drug, which has been avail- generics,” Gottlieb wrote. The voucher system proposed by Gottlieb runs able for decades overseas as a generic somewhat parallel to the one proposed in the Lower Drug Costs Through corticosteroid therapy. US patients able Competition Act (H.R. 749), sponsored by Rep. Kurt Schrader, D-Ore., and to re-import the drug have been paying Gus Bilirakis, R-Fla. The bill would create a six-month priority review path- roughly $1,000 per year. CEO Stuart way for ANDAs for drugs with only one sponsor marketing them already, Peltz said during the PTC conference products on FDA’s drug shortage list or possibly first generics. The spon- call’s question-and-answer period, “We sors could then receive a priority review voucher once the drug is approved. appreciate that [Emflaza’s] pricing is re- [email protected], 13 March 2017 ceiving a lot of attention and we believe that a change needs to be made.” PTC’s investors already were concerned about the South Plainfield, New Jersey-based Consumer class actions also have been prices. The Minnesota Attorney General firm’s decision to go against the FDA filed against Novo, Sanofi and Eli Lilly jumped in and launched an investiga- and use the “file over protest” path- & Co. alleging their discount prices with tion. Novo and Sanofi reported in Febru- way to re-file the new drug application pharmacy benefit managers were anti- ary 10-K SEC filings that in January this (NDA) for Translarna after receiving a competitive. The lawsuits arose after the year they received civil investigative de- refuse-to-file letter for the drug in 2016. US Attorney’s Office for the Southern mands from the Minnesota AG’s office [email protected], 16 March 2017 District of New York issued civil investi- requesting documents and information gative demands (CIDs) to Novo and Sa- “relating to pricing and trade practices” nofi in March 2016 for documents relat- for Novo’s long-acting insulin products, US Insulin Pricing Probe Clouds ing to their contracts and relationships including Levemir (insulin glargine) and with pharmacy benefit managers involv- Tresiba (insulin degludec), and Sanofi’s Prospects for Novo Nordisk ing insulin products. Lilly also received insulin glargine products Lantus and While insulin makers are facing US a CID regarding unspecified products. Toujeo. The potential impact of the in- government investigations of their pric- Senator Bernie Sanders, I-Vt., and Rep- vestigations can’t be gauged at this early ing and relationships with pharmacy resentative Elijah Cummings, D-Md., stage. “It depends on what the specific benefit managers, Novo Nordisk AS is subsequently sent a letter to the Depart- allegations are and if there is any sub- also dealing with a flurry of lawsuits al- ment of Justice and Federal Trade Com- stance to them,” a former Department leging the Danish diabetes fighter col- mission in November asking them to in- of Justice prosecutor said. sIt is also un- luded with other insulin manufacturers vestigate whether insulin manufacturers clear whether the probes will have any to increase prices, artificially inflate its have colluded or engaged in anticom- effect on the price of insulin. financial results and mislead investors. petitive behavior in setting their drug [email protected], 17 Mar 2017

20 | Scrip intelligence | 24 March 2017 © Informa UK Ltd 2017 EMERGING COMPANY PROFILE

iTeos: IO Therapies For Hot And Cold Tumors SUKAINA VIRJI [email protected]

With the immuno-oncology space a A2A AND TIGIT battleground for large pharmaceuti- This year iTeos is aiming to raise a €40m series cal companies, surely there isn’t much a C; it plans to bring in €15-20m from existing small biotech can offer? iTeos Therapeu- investors. This money will be used to push tics, a 2011 spin off from Ludwig Cancer iTeos earlier programs: A2A and TIGIT, into Research, believes otherwise, CEO and Phase I in 2018. If successful, iTeos could be founder Michel Detheux told Scrip. ready for an IPO in 2019, believes Detheux. The A2A receptor antagonist program is Teos is targeting hot and cold tumors. based on the fact that adenosine inhibits the “This concept in targeting the tumor mi- immune response through A2A receptors. icroenvironment is becoming more and However, A2A receptor antagonists in the more important in the field of oncology,” tumor microenvironment can prove prob- said Detheux. lematic as the concentration of adenosine in Tumors can be labelled as ‘hot’ or ‘cold’ tumors is 10 to 15 fold higher than in the brain, or somewhere in between, depending on Michel Detheux meaning the introduction of A2A recep- how densely they are infiltrated by lympho- tor antagonists affects the brain more than cytes, according to Detheux. Typically, hot as key targets in the cancer immunotherapy the tumor. Many A2A receptor antagonists tumors are associated with a better prog- field. iTeos was the first spin-off created by in development for oncology applications nosis, because the presence of lymphocytes the Ludwig in which it invested cash, noted were initially developed for the treatment of suggests that the immune system has rec- Detheux. Two years later, the programs were Parkinson’s disease – not the ideal starting ognized that the tumor is ‘foreign’ on some out-licensed to Pfizer at the lead stage. point in this setting, Detheux pointed out. level, despite not being able to clear it effec- Compared to the competition, which iTeos has developed compounds with lim- tively. ‘Cold’ tumors are characterized by little includes Incyte Corp., NewLink Genetics ited CNS penetration and has some promis- or no infiltration of immune cells, and these Corp. (partnered with Roche’s Genentech ing preclinical data from cancer models. It patients usually have a poorer prognosis. Inc.), Bristol-Myers Squibb Co. (through its plans to select a candidate in the coming “Most current therapeutic programs are Flexus acquisition) and Merck & Co. Inc. months to take into clinical testing in 2018. targeting hot tumors, trying to activate the (through its IOmet Pharma acquisition), iTeos also has a TIGIT antibody program immune cells that have infiltrated the tu- “our IDO1 compound is differentiated by that could be ready for the clinic in 2018. mor. If you are targeting a cold tumor, you a very favorable PK profile with a long The diversity of small molecules and anti- are trying to create an immune response half-life but also penetration to the brain bodies is important to the company, em- – that was the purpose of the entire effort which could be very useful to control phasized Detheux. behind cancer vaccines.” brain metastases,” explained Detheux. TIGIT is a co-inhibitory receptor expressed iTeos’ later stage programs – one licensed “When iTeos was founded, there was only on the surface on T lymphocytes. The bind- to Pfizer Inc. and two which it hopes to take the knowhow: no IP and nothing to out- ing of an antibody to it blocks a negative into the clinic next year (a small molecule license.” iTeos conducted classical high signal to immune cells via one mechanism, A2A receptor antagonist and a TIGIT anti- throughput screening, hit-to-lead assays, and stimulates immune cells via another. body) – are focused on ‘hot’ tumors, with the lead optimization, and characterization of Genentech has a TIGIT program in Phase I. aim of activating the lymphocytes already a preclinical candidate, which went on to inside the tumor to do their job of clear- be selected by Pfizer. STING AGONIST ing up the ‘foreign’ cells. However, an earlier Pfizer took the IDO1 program into Further back in development is iTeos’ STING STING agonist project is looking at the ‘cold’ Phase I testing in patients with brain can- agonist program. The addition of these tumor environment, with the aim of creat- cer (malignant gliomas) in September compounds to ‘cold’ tumor cells can trans- ing immunogenicity. 2016. The candidate, PF-06840003, has form them into ‘hot’ tumors. This is thought iTeos was founded as a spinoff from Lud- been tested in combination with PD-L1 to be a key factor in making these tumors wig Cancer Research as a new initiative. antibodies and other immune-oncology more susceptible to IO treatment. Aduro “They agreed to try a dedicated company compounds and appears to boost anti- and Novartis are collaborating on a STING that would take some of the Ludwig’s know- tumor immune response. agonist in Phase I. how – the IDO1 and TD02 programs – and Since signing the deal with Pfizer, iTeos has STING agonists require tumor-specific de- be the champion of these programs.” worked hard to build a sustainable pipeline, livery, and iTeos signed a nanoparticle deliv- The two enzymes IDO1 (indoleamine-2,3- entering an antibody platform access deal ery partnership with Cristal Therapeutics last dioxygenase) and TDO2 (tryptophan-2,3- with Adimab in the US and a targeted deliv- year. The program, along with a galectin-3 an- dioxygenase) break down the essential ery platform access deal with Cristal Thera- tibody program, are at the lead identification amino acid tryptophan, and have emerged peutics in The Netherlands. stage. Published online 15 March 2017

scrip.pharmamedtechbi.com 24 March 2017 | Scrip intelligence | 21 PIPELINE WATCH

Scrip’s weekly Pipeline Watch tabulates the most recently reported late-stage, Phase III clinical trial developments for the more than 10,000 CLICK drug candidates under active research worldwide. To see changes to the Visit the Pipeline Watch webpage at progress of product candidates further back in the development pipeline, scrip.pharmamedtechbi.com for all and a table of the week’s product approvals, please visit our Pipeline the week’s changes to the industry’s R&D pipeline Watch webpage at scrip.pharmamedtechbi.com.

Selected clinical trial developments for the week 10–16 March 2017

LEAD COMPANY/PARTNER COMPOUND INDICATION COMMENTS Updated Phase III Results ovarian cancer, BRCA SOLO 2; progression-free survival benefit AstraZeneca PLC Lynparza (olaparib) mutation, relapsed confirmed . Tesaro Inc. niraparib recurrent ovarian cancer NOVA; results of secondary endpoints presented . Ameluz Photodynamic therapy, effective and well Biofrontera AG actinic keratosis (5-aminolevulinic acid) tolerated. Phase III Interim/Top-line Results Amgen Inc. Repatha (evolocumab) dyslipidemia Reduced the need for LDL-C apheresis. RBP-7000 (risperidone Indivior PLC schizophrenia Clinically effective and durable responses. monthly depot) Phase III Initiated ALKS8700 Study will evaluate gut tolerability Alkermes PLC multiple sclerosis (monomethyl fumarate) versus Tecfidera. Jazz Pharmaceuticals PLC JZP-258 narcolepsy, cataplexy In 60 centers in the US and EU. Charcot-Marie-Tooth Pharnext SAS PXT3003 PLEO-CMT-FU; a Phase III extension study. disease LSK BioPartners Inc. apatinib gastric cancer ANGEL; in advanced or metastatic disease. Phase III Announced chronic obstructive AstraZeneca PLC PT010 To be compared with PT009. pulmonary disease Novartis AG/Otsuka Kisqali (ribociclib) breast cancer EarLEE-2; with endocrine therapy. Holdings Co. Ltd. FOURIER OLE; long term safety study in patients Amgen Inc. Repatha (evolocumab) dyslipidemia with CV disease. Updated Phase II Results Genkyotex SA GKT137831 diabetic nephropathy Mixed results, improved secondary endpoints. TiGenix NV AlloCSC-01 acute myocardial infarction CAREMI; well tolerated. Clovis Oncology Inc. Rubraca (rucaparib) advanced ovarian cancer ARIEL2; new analyses of patient subsets . Phase II Completed Improved 12-month survival rate, Phase III Advaxis Inc. axalimogene filolisbac cervical cancer planned. Phase II Interim/Top-line Results diffuse large B-cell SADAL; response rates strong, amended to a Karyopharm Therapeutics Inc. selinexor lymphoma single arm study. A neuropeptide Y5 antagonist, induced weight Shionogi & Co. Ltd. S-237648 obesity loss but not clinically meaningful. Firdapse (amifampridine Catalyst Pharmaceuticals Inc. myasthenia gravis Significant effects on co-primary endpoints. phospate) severe refractory atopic Galectin Therapeutics Inc. GR-MD-02 Clinical responses seen, well tolerated. dermatitis Source: Biomedtracker

22 | Scrip intelligence | 24 March 2017 © Informa UK Ltd 2017 APPOINTMENTS

Smart Matrix Limited (SMLC)., a com- Biosciences as head of clinical operations vice president, corporate development pany focused on wound healing, has and development. and strategy. Adams joins bluebird from appointed Andy Hill CEO. Meanwhile, Evelo Biosciences, where he was senior board member Leonor Stjepic has Rare genetic diseases focused Thera- vice president of CMC and before this he stepped down to focus on other respon- chon AG. has appointed Maarten was vice president of technical strategic sibilities. Hill has more than 30 years of Kraan, AstraZeneca’s former vice presi- product development at Alexion Phar- experience in the medical technology dent, head of innovative medicines and maceuticals. Previously, Smith-Farrell was industry and previously, he was CEO of respiratory and inflammation, chief medi- vice president business development Deltex Medical plc. cal officer. Before AstraZeneca, Kraan was transactions at Merck Inc. and before this vice president, head of clinical research she was vice president of strategic trans- IRX Therapeutics Inc. has appointed bi- and experimental development inflam- actions at Pfizer Inc. otech industry veterans Mark Leuchten- mation at Hoffman La Roche. Prior to this, berger and Monil Shah to president, he was vice president, immunosciences ASIT Biotech, a Belgian clinical stage bi- CEO and director and chief operating of- at Bristol Myers Squibb and began his opharmaceutical company focused on the ficer, respectively. IRX’s founder and prior pharma career at Schering Plough. treatment of allergies, has appointed Gerd CEO, John W. Hadden, will continue on at Zettlmeissl chair of its board. Since 2011, the the company as a director. With over Mission Therapeutics, a company focused Zettlmeissl was an independent director of 20 years’ experience, Leuchtenberger was on cancer and neurodegenerative diseases, ASIT and previously, he was CEO of Inter- president, CEO and member of the board has appointed Anne Phelan as senior cell AG, an Austrian vaccine company that at Chiasma, Acusphere Inc. and Rib-X vice president, head of discovery research. merged with the French company Vivalis, to Pharmaceuticals Inc. (now Melinta Thera- Phelan joins Mission from BenevolentAI (for- create Valneva. peutics Inc.). He has also been president merly Stratified Medical), where she was VP, and CEO of Targanta Therapeutics Corpo- drug discovery. Before this, she held various Kiadis Pharma, a biopharma company ration and Therion Biologics Corporation. positions within Pfizer including chief oper- developing immunotherapy treatments Shah brings more than 17 years of phar- ating officer and head of pharmacology at for blood cancers and blood disorders, has ma and biotech experience in oncology Pfizer Neusentis in Cambridge, UK. appointed Jan Feijen chief operating of- to IRX and most recently, he was medical ficer – effective April 1, 2017. Most recently, affairs lead for immuno-oncology at Bris- Derek Adams has joined bluebird bio Feijen was vice president manufacturing tol Myers Squibb. He started his career at Inc. as chief technology and manufactur- and technical operations, platform lead Novartis, in the oncology early develop- ing officer; andJoanne Smith-Farrell has vaccines and advanced therapies at Jans- ment group and later co-founded Ventrus also been appointed as bluebird’s senior sen (a Johnson & Johnson company). Scrip ELEANOR MALONE @SCRIPELEANOR LUCIE ELLIS @SCRIPLUCIE YING HUANG [email protected] [email protected] [email protected] ALEXANDRA SHIMMINGS @SCRIPALEXS LUBNA AHMED @SCRIPLUBNA JUNG-WON SHIN [email protected] [email protected] [email protected] SUKAINA.VIRJI @SCRIPSUKI PAUL WILKINSON @PAUL__WILKINSON BRIAN YANG [email protected] [email protected] [email protected] ANJU.GHANGURDE @SCRIPANJUG JOHN HODGSON @SCRIPJOHN [email protected] [email protected] All stock images in this publication MANDY JACKSON @SCRIPMANDY MIKE WARD @SCRIPMIKEWARD courtesy of www.shutterstock.com [email protected] [email protected] unless otherwise stated. JOANNE SHORTHOUSE @SCRIPJO PETER CHARLISH @PETERCHARLISH Customer Services [email protected] [email protected] Tel: +44 (0)20 7017 5540 FRANCESCA BRUCE @SCRIPFRANCESCA JOHN DAVIS @JOHN023DAVIS or (US) Toll Free: 1 800 997 3892 [email protected] [email protected] Email: [email protected] STEN STOVALL @STENSTOVALL EMILY HAYES @EMILYKATEHAYES [email protected] [email protected] To subscribe, visit IAN SCHOFIELD @SCRIPIANS JESSICA MERRILL @JESSCIAMERRILL scrip.pharmamedtechbi.com [email protected] [email protected] To advertise, contact ASHLEY YEO @ASHLEYPYEO JOSEPH HAAS [email protected] [email protected] [email protected] Scrip is published by Informa UK Limited. MARY JO LAFFLER IAN HAYDOCK ©Informa UK Ltd 2017: All rights reserved. [email protected] [email protected] ISSN 0143 7690.

scrip.pharmamedtechbi.com 24 March 2017 | Scrip intelligence | 23 Visit us at Booth #F25

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