Teva Lands a CEO: Can Schultz Replicate

22 September 2017 No. 3872

Scripscrip.pharmamedtechbi.com Pharma intelligence | informa July prior to releasing disappointing second- Kare Schultz is moving from Lundbeck to Teva quarter financials on Aug. 3. The Israeli company has been searching for a CEO for seven months, with former chair Yitzhak Peterburg standing in on an interim basis since Erez Vi- godman fell on his sword in February 2017 after failing to turnaround the company in three years at the helm. Schultz could benefit from being an industry insider, a change from Vigodman who previously worked in the generic crop chemical sector. “While Schultz does face numerous challenges (i.e. generic and branded segments are facing headwinds), we think having an experienced pharmaceutical executive join the company is the single most important item,” wrote BTIG analysts in a same- day note. Teva Pharmaceutical Industries Pharmaceutical Teva “Schultz’s long track record in the pharmaceutical industry combined with his success in turning around Lundbeck seem to Teva Lands A CEO: Can Schultz make him a strong candidate to lead Teva’s recovery,” Credit Suisse analysts said. Credit Suisse’s Vamil Divan highlighted Replicate Lundbeck Success? in particular the incoming CEO’s ability to ELEANOR MALONE [email protected] launch new products successfully while “ag- gressively managing expenses” – something eva Pharmaceutical Industries Teva has been struggling for some years that could stand him in good stead as Teva Ltd.’s new CEO Kåre Schultz has es- to establish a coherent strategy for future prepares for the launches of fremanezumab Ttablished a solid track record in the growth, especially as the US generic drug and rolls out Austedo (deutetrabenazine) for short time he’s been overseeing the ratio- sector has come under intense pressure. a recently-approved tardive dyskinesia in- nalization of Danish neurology drug special- One diversified opportunity is the compa- dication. (Also see “Teva Set For Immediate ist Lundbeck Inc. Whether he can replicate ny’s CNS franchise, including the branded US Launch Of Austedo In Tardive Dyskinesia” the same success at a very different kind of multiple sclerosis drug Copaxone (glatiram- Scrip, 31 Aug, 2017.) company – the world’s biggest generic drug er acetate) and the late-stage migraine pre- However, Teva has other challenges in company – is now the question. Lundbeck’s vention treatment fremanezumab, though less familiar territory for Schultz, who prior share price has more than tripled during that business is facing competition from to joining Lundbeck had a long career in his time as CEO of the company, with sales both generics and innovative new drugs. senior leadership at diabetes and hemo- rising by a healthy 16% in those two years Investors welcomed the appointment of a philia drug maker Novo Nordisk AS, where (as of the end of 2016) and profits, margins CEO after a lengthy search, with Teva’s share he was once tipped for the CEO position. and cash flow restored to vitality. His golden price showing some recovery, up 16.6% on (Also see “Ex-Novo Nordisk protégé Schultz becomes Lundbeck CEO” Scrip, 6 May, 2015.) touch at Lundbeck, experience in the cen- the Tel Aviv stock exchange on Sept. 11. Pricing pressure in the US generics market tral nervous system (CNS) sector and history Nonetheless, the stock still is trading down dealing with a patent cliff stand in his favor. substantially from where it was trading in CONTINUED ON PAGE 12

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Rheumatoid Arthritis ESMO Meeting Company Shakeup AbbVie’s JAK Inhibitor Looks Good Melanoma and breast cancer battles Alexion Restructuring Deemed A But CV Specter Looms (p5) play out in Madrid (p8-12) Necessary Evil (p17) IN THIS ISSUE

from the editor [email protected]

At last, Teva Pharmaceutical Industries looks to be the meantime Teva executives must continue to take de- moving on key strategic aims. Like having a permanent cisions without knowing the company’s future strategy. CEO. With Lundbeck’s widely respected Kåre Schultz Last week we reported on Allergan’s surprising part- signed up, even if his start date has yet to be agreed, the nership with the Saint Regis Mohawk Tribe, which mood around the embattled Israeli generics and spe- made the initial approach (according to Allergan) with cialty drug giant has brightened. a “sophisticated opportunity to strengthen the defense The subsequently announced sale of its Paragard intra- of [its dry eye treatment] Restasis intellectual property”. uterine contraceptive business for $1.1bn and separate Mylan, which is among companies challenging Aller- divestment of its remaining specialty women’s health gan’s Restasis patents, is now branding that arrange- business for $1.38bn will enable Teva to pay down debt. ment a “desperate tactic” and examining it with a view However, Schultz will still be expected to deliver bold and to establishing if it is “anti-competitive” (see p18). The decisive changes, and to complement the current non- Saint Regis Mohawks see this deal as a way of diversify- core business disposal plan and recent job cuts, positive ing their economic foundation beyond casino revenues. actions to grow the business will need to be forthcom- If they manage to pull it off, watch this space for further ing as soon as he can figure them out. The uncertainty unusual pharma partnerships – and more outrage from over when he will join Teva is a challenge though, as in thwarted competitors.

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EDITORS IN CHIEF Ian Schofield EDITORIAL OFFICE Eleanor Malone (Europe) Vibha Sharma Christchurch Court Denise Peterson (US) Joanne Shorthouse 10-15 Newgate Street London, EC1A 7AZ Ian Haydock (Asia) Sten Stovall US CUSTOMER SERVICES EXECUTIVE EDITORS Michael Cipriano Tel: +44 (0)20 7017 5540 COMMERCIAL Derrick Gingery or (US) Toll Free: 1 800 997 3892 Alexandra Shimmings (Europe) Joseph Haas Email: clientservices@ Mary Jo Laffler (US) pharmamedtechbi.com Emily Hayes Mandy Jackson POLICY AND REGULATORY TO SUBSCRIBE, VISIT Cathy Kelly Maureen Kenny (Europe) scrip.pharmamedtechbi.com Nielsen Hobbs (US) Jessica Merrill Brenda Sandburg TO ADVERTISE, CONTACT [email protected] Bridget Silverman EUROPE Sue Sutter Lubna Ahmed Neena Brizmohun Francesca Bruce ASIA John Davis Anju Ghangurde Lucie Ellis Ying Huang All stock images in this publication Kevin Grogan Jung Won Shin courtesy of www.shutterstock.com John Hodgson Brian Yang unless otherwise stated

2 | Scrip | 22 September 2017 © Informa UK Ltd 2017 Merck Cancer Chief GSK’s COPD Combo Wins Reflects 13

J&J’s HCV Departure

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exclusive online content inside: COVER / Teva Lands A CEO: Can Schultz Replicate J&J’s Guselkumab Nears Crowded EU Psoriasis Market Lundbeck Success? After CHMP OK 5 AbbVie’s New Generation JAK Inhibitor Looks Good But http://bit.ly/2yk6Bf1 CV Specter Looms Janssen-Cilag/MorphoSys’s potential first-in-class psoriasis therapy has received a positive approval recommendation 6 Merck & Co Cancer Chief Reflects on ‘Foundational’ Keytruda from Europe’s top scientific advisory panel, and could become a blockbuster product despite the cluttered and changeable 7 GSK’s COPD Triple Combo Wins EU Nod state of the dermatology sector. 8 New Melanoma Frontier Opens To Bristol’s Opdivo 2017 Filing For Shionogi’s Novel Flu Drug In Japan On And Novartis/Glaxo’s BRAF/MEK Combo Back Of Strong Phase III Data 10 Clovis CEO Sees Rosy Future With Rubraca http://bit.ly/2jCSsq2 Shionogi is on track to file its novel flu treatment S-033188 11 Lilly’s Abemaciclib On Par With Ibrance In Breast Cancer, But with regulators in Japan by the end of the year on the back of Not ‘Clearly Superior’ positive Phase III data. 13 With J&J’s Departure From HCV, Gilead Stands Alone In ‘Nuc’ Field Clinigen Takes Aim At Unlicensed-To-Licensed Strategy With Quantum Buy 14 Boehringer Taps Gubra For Early-Stage Obesity Deal http://bit.ly/2xf2um0 Extending its business in continental Europe, in niche generics 14 Teva’s US IUD Brings In $1.1bn and in the further development of unlicensed medicines are some of the drivers of Clinigen’s latest proposed acquisition. 15 Sanofi And Regeneron Hit Asthma Phase III Endpoints With Dupixent

PROSPECTs Futile For Bavarian Nordic’s Prostvac 16 Will Keytruda Price Differential Really Count In India? Cancer Vaccine http://bit.ly/2f4pKt3 17 Alexion Restructuring Deemed A Necessary Evil The Phase III PROSPECT study’s data monitoring committee decides against continuing after interim analysis. The fall-out 18 Mylan Calls Allergan Restasis Patent Deal A ‘Desperate Tactic’ could hit Bavarian Nordic’s CV301 too. 19 Bayer’s Aliqopa Approval Gives PI3K Class A Second Chance in Follicular Lymphoma Halozyme Lands Largest Enhanze Deal To Date With Bristol 20 Novo Nordisk Prepares Victoza’s China Launch http://bit.ly/2yjXAT6 Bristol will pay $105m up front and as much as $1.76bn in 21 Pfizer Poised To PROSPER From Xtandi milestone fees to use the Enhanze technology in drugs against 22 Pipeline Watch up to 11 immuno-oncology targets. Also, Roche will pay up to $190m to add a target to an existing partnership. 23 Santhera Shares Sink On Duchenne Setback in Europe

Tesaro Pumped As PARP Inhibitor Zejula Gets 23 Appointments CHMP Nod http://bit.ly/2hc2YQJ While AstraZeneca’s rival drug Lynparza is catching up across the Atlantic, this likely approval for Tesaro’s ovarian cancer drug will boost the US firm as it aims to make a strong start in the @PharmaScrip /scripintelligence European market. /scripintelligence /scripintelligence

scrip.pharmamedtechbi.com 22 September 2017 | Scrip | 3 HEADLINE NEWS

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CKD BiO - SERVICE AREA • Strain development from wild AbbVie’s New Generation JAK Inhibitor Looks Good But CRO/CMO Specialist type screening with broad Delivering the life-saving fermentation spectrum of microorganisms CV Specter Looms (Streptomyces, Fungi, ALEX SHIMMINGS [email protected] technology into the world Bacteria, Yeast) op-line data from the second of six SELECT-NEXT, AbbVie says the data further (tofacitinib), which is currently the only JAK • Novel process development & Phase III studies of AbbVie Inc.’s support the potential for upadacitinib to be inhibitor approved to treat RA (launched in Optimization to industrial scale T investigational oral JAK1-selective a meaningful treatment option for difficult to 2012). Another similar product in develop- • Cost savings via most optimal inhibitor, upadacitinib (ABT-494), SELECT- treat patients who do not respond adequate- ment is Gilead Sciences Inc./Galapagos BEYOND, show that it hit its endpoints in pa- ly to biologicals. The top-line SELECT-NEXT NV’s filgotinib (previously partnered with Ab- scaled operation tients with moderate to severe rheumatoid data were released in June. (Also see “AbbVie bVie), also in Phase III for RA. • Analytical method arthritis who had not responded to, or were May Be Poised For An Oral RA Smack Down” Jefferies analysts said this second lot of intolerant of, biological disease-modifying Scrip, 7 Jun, 2017.) positive Phase III data for upadacitinib led development & Process antirheumatic drugs (bDMARDs). Upadacitinib is a key part of AbbVie’s strat- them to believe the drug “has the potential validation However, reports of two deaths in the egy to offset expected biosimilar competi- to be the best-in-class JAK inhibitor,” and they • Impurity characterization & study in patients receiving the drug – one tion to its top-seller Humira (adalimumab). remain unconcerned by the PE events. from pulmonary embolism – plus a second Filings are generally expected in the second “The deaths were considered by inves- Stability studies (non-fatal) PE case have raised questions over half of 2018. tigators to have no reasonable possibility • Full support of RA documents its cardiovascular side-effect profile. of being related to upadacitinib at the This subject is particularly sensitive given DATA DESCRIBED time of initial reporting. We find it reas- • Other customized services the experience of Eli Lilly & Co./Incyte SELECT-BEYOND tested two once-daily suring that PE/DVT rates in the Phase III Corp.’s rival product baricitinib, which has doses (15 mg and 30 mg) of upadacitinib studies remain consistent with the back- been delayed in the US partly because of in adult patients with moderate to severe ground rate for the RA population, and CORE TECHNOLOGY concerns over thromboembolic events. Lilly rheumatoid arthritis who were on a stable that no PE cases have been observed in AND RESEARCH and Incyte have just revealed their intention dose of conventional synthetic DMARDs (cs- the atopic dermatitis or Crohn’s studies,” to refile their product by the end of January DMARDs) and had an inadequate response they said in a research note, adding that Fermentation & Synthesis Fermentation 2018, after its progress at the US FDA was or intolerance to bDMARDs. The initial re- there were no cases seen of either PE or for Intermediates/APIs/NCEs • Classical mutation stymied by an April complete response let- sults show that after 12 weeks of treatment, DVT in SELECT-NEXT. • Genome shuffling ter, which also cited concerns over dosing. both upadacitinib doses met the study’s pri- Jefferies estimate peak sales of $2.5bn for (Also see “Lilly/Incyte’s JAK Inhibitor Baricitinib mary endpoints of ACR20 and low disease upadacitinib in RA, but analysts at Leerink are • Gene manipulation Poised For FDA Approval After All” Scrip, 30 activity (LDA). Secondary endpoints includ- more conservative in their forecasts, putting CAPABILITY • Omics technology Aug, 2017.) ed the more stringent ACR50 and 70 scores. peak sales at $1.6bn in 2027, and more than • Fermentation: 1,500 m3 Fermentors (12 m3 to 100 m3) AbbVie stressed that SELECT-BEYOND re- The 12-week results were statistically sig- $1bn in 2022, lining up with consensus esti- • Filtration vealed no new safety signals and that across nificant compared to placebo (p<0.001) for mates of $1.2bn sales by 2022. 3 • Synthesis: 26 m Reactors • Condensation the SELECT RA program, including both the all comparisons except ACR70 for the 15 mg Leerink analysts say investors are likely to (plus 1 m3 Reactors for high potency APIs) placebo-controlled and extension periods, dose. comb over every PE and DVT event follow- • Chromatographic column the rate of deep vein thrombosis (DVT) and Results continued to be encouraging ing the baricitinib delay. “Even a low rate • Probiotics: 6 m3 Fermentors PE remained consistent with the background through week 24 but comparisons with pla- of significant thromboembolic or cardio- Probiotics rate for the RA patient population. cebo cannot be made at week 24, since all vascular events would be alarming to in- It is focusing on the efficacy seen with the placebo patients received either upadaci- vestigators and to treating physicians, and • Development of health ADDITIONALLY product, especially the proportion of patients tinib 15 mg or 30 mg beginning at week 12. there seems sufficient consistency in these functional microorganism who achieved clinical remission by week 12 Efficacy-wise, the results for upadacitinib reports and the imbalances to scrutinize • Beyond international GMP standards • Culture optimization and 24, despite having inadequate responses compare favorably with the RA-BUILD and them all closely.” (Approvals of USFDA, AIFA, TGA, WHO, PMDA, etc) with previous biologic therapies. Together RA-BEACON studies of baricitinib and the Analysts at Biomedtracker said the results • Coating technique for with the previously reported results from ORAL-Step study of Pfizer Inc.’s Xeljanz were positive but noted they may not be • Commercial activity over 60 countries stabilization part of the initial filing in RA. Instead, the initial regulatory filing will likely be based on the • Microbiome study • Strong collaboration with Multinational Companies NEXT and COMPARE studies in conventional DMARD failures whereas this study evaluated Synthesis LET’S GET SOCIAL only biologic DMARD failures, they said. Published online 12 September 2017 Best qualified CRO & CMO Partner, CKD BiO Corporation • High potency products We are tweeting, liking and sharing the latest industry news and with unique customized service 8, Chungjeong-ro, • Hydrogenation insights from our global team of editors and analysts, join us! 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Merck & Co Cancer Chief Reflects on ‘Foundational’ Keytruda KEVIN GROGAN [email protected]

chemotherapies was 19.0 months, com- note-059 trial showed a promising response Oncology development head Roger Dansey pared with 8.9 months for the chemo arm. rate in metastatic gastric cancer treated in Dansey said the data were impressive the third line or beyond, prompting inves- and noted that the hazard ratio for overall tigator Ian Chau of the Royal Marsden Hos- survival improved to 0.59 in the ESMO up- pital in London to say “the likelihood is that date from 0.69 as reported from an earlier pembrolizumab will become a standard update at the American Society of Clinical treatment option in this setting in the near Oncology meeting in June. “It suggests that future.” It was filed for that indication in the this approach of giving Keytruda plus che- US earlier this year. mo upfront is really a winning approach in Dansey also spoke about Keynote-040 terms of tighter disease control and improv- in head and neck cancer: “The first trial ac- ing survival.” tually where we have missed any statistical Analysts at Leerink approve of the ap- endpoint.” However, the 19% improvement proach, saying that Keynote-021G “may be in overall survival only narrowly fell short able to serve as the confirmatory trial to “and showed there is a very clear biomarker convert this regimen’s accelerated approval effect with PD-L1.” Lead investigator Ezra to full approval” in the US. They noted that Cohen, speaking at an ESMO press confer- overall response rate for the combo arm re- ence said that even though the study did mains at 57% (versus 32% for chemo only) not meet its primary endpoint, “I still think it and importantly, the PFS benefit appears to is a positive trial. It reinforces that pembroli-

Merck & Co & Merck be maintained beyond one year, with the zumab should continue to be offered as an rate dropping off by only 5% (57% to 52%) important option for all patients with this between 12 and 18 months - the chemo devastating disease.” (Also see “Merck’s Key- t is only three years ago that Merck & arm drops from 37% to 29% during the truda Gets Benefit Of Doubt, Despite Failing in Co. Inc. got its first approval forKeytruda same period. Head & Neck” Scrip, 24 Jul, 2017.) I(pembrolizumab) in melanoma and data It is clear that there is still much mileage presented at the European Society for Medi- EU OKAY FOR BLADDER CANCER left in the Keynote clinical program and cal Oncology congress in Madrid has high- Onto bladder cancer, where a couple of Dansey told Scrip that “none of our studies lighted how dominant the PD-1 inhibitor days before ESMO Merck got European ap- have closed, not even the original one – we has become in such a short space of time. proval for Keytruda for use as monotherapy have a commitment, an interest and, I think, Speaking to Scrip at the congress, Roger for the treatment of locally advanced or a responsibility, to report long-term out- Dansey, head of the company’s clinical de- metastatic urothelial carcinoma in adults comes for all of these trials.” velopment in oncology, noted the huge who have received prior platinum-contain- amount of trials looking at Keytruda and ing chemo. It also got the nod to be used COMBO WITH INCYTE’S IDO1 possible combinations, pointing out that in adults who are not eligible for cisplatin- SHOWS PROMISE there are in excess of 500 studies listed on containing chemo. Dansey also expressed satisfaction with clinicaltrials.gov and the company itself is Dansey noted that the second, front-line the results of a keenly watched Phase I/ running over 40 registration trials. ESMO approval, which was based on Phase II data II trial in melanoma combining Keytruda saw some new data being released on the from the Keynote-052 trial, is particularly with Incyte Corp.’s IDO1 enzyme inhibitor Merck blockbuster and some important up- striking. “We were very pleased and excited epacadostat. An updated analysis in Ma- dates on previous studies. that the European Medicines Agency saw its drid showed that among all patients with One of the most important was an up- way to approving a non-randomized trial,” advanced melanoma, including treatment- date on the Keynote-021 (cohort G) trial he said, adding that this is in a high unmet naïve and -experienced, the overall re- investigating Keytruda in combination with need group, patients aged over 75-85 who sponse rate was 56% (n=35/63) in patients pemetrexed and carboplatin in previously cannot tolerate heavy chemo. “They may treated with the combo. Median PFS was untreated advanced non-squamous non- only have gone to palliative care and now 12.4 months and a complete response was small cell lung cancer, with or without PD-L1 Keytruda is now an option.” seen in nine patients. expression. With an additional five months Another updated Keynote trial (“we are Dansey said that if “IDO1 turns out to be of follow-up, median progression-free sur- into the 700s now,” Dansey quipped) was an efficacious intervention, it’s going to be a vival for Keytruda plus the aforementioned in stomach cancer. One cohort of the Key- major advance because it is very safe.” Unlike

6 | Scrip | 22 September 2017 © Informa UK Ltd 2017 ESMO/APPROVALS

anti-CTLA-4 therapies, which “clearly carry some safety baggage,” he noted that the GSK’s COPD Triple Combo Wins adverse event with IDO1 is rash. “In general, you add something you expect something with a greater safety burden, so IDO1 has a EU Nod very effective profile, both in terms of effi- LUCIE ELLIS [email protected] cacy and safety.” The oncology chief noted that early-stage laxoSmithKline PLC and partner powder inhaler. It is the first once-daily disease is a key focus for Merck and a neoad- Innoviva Inc. have won a positive single inhaler triple therapy to be granted juvant approach, saying that “as you move Grecommendation in Europe for the a positive opinion by the CHMP; Trimbow to earlier and earlier treatment, you have an approval of Trelegy Ellipta, a triple combina- is dosed twice daily. immune system that is relatively intact that tion therapy for adult patients with moder- A second version of GSK’s closed triple hasn’t been beaten up by other therapy ate to severe chronic obstructive pulmonary combination COPD therapy was also [and] that is the time to get the best treat- disease (COPD). given a positive recommendation by the ment effect.” Some of the trials that Merck is running GSK’s triple combination COPD therapy in the neo-adjuvant/adjuvant setting in- whirls through CHMP clude Keynote -091, a Phase III study in patients with stage IB/II-IIIA NSCLC (estimated primary completion date is Aug. 2021), Keynote-054 in melanoma (May 2018), Key- note-522 for triple negative breast cancer (Nov 2018). Keynote-664 for renal cell carcinoma (Nov. 2022) and Keynote-585 for gastric cancer (July 2023). When asked whether there are too many trials being conducted, looking at a jaw- dropping number of combinations, Dansey told Scrip that “Keytruda is foundational and Dawes Graeme Shutterstock: there is every reason to believe that the PD-1 axis is pivotal and once you accept A green light from the European Medi- CHMP under the brand name Elebrato El- that, you have to build on that, it would cines Agency’s scientific committee, the lipta. Patrick Vallance, GSK’s president of make no sense not to leverage it with other CHMP, is a boost of confidence for the two R&D, said, “We believe once-daily single combinations.” He added that when Merck firms that Trelegy Ellipta will be able secure a inhaler triple therapy, if approved, would sees an attractive combination, be it IDO1 regulatory approval in the US in the coming provide an important option for appro- or oncolytic viruses, the firm is prepared to weeks. The product is expected to be the priate patients with COPD who are re- back studies but “at some point, there will first triple combination therapy to market ceiving ICS/LABA and require additional have to be a funnel, it can’t be never-ending for COPD in the US if it is successfully ap- bronchodilation, avoiding the need for development.” proved later this year. multiple inhalers.” There will come a point where choices In the EU though, Chiesi Farmaceutici The new triple therapy options in have to be made, he said, “Where you say, SPA’s Trimbow (beclometasone/formoter- COPD are attractive because the most se- ‘Yes, that looks good but in the environment ol/glycopyrrolate) was the first of three in- vere patients require all three medicines you are in, it may not be good enough to coming triple combination drugs on the together, but Trimbow and Trelegy will beat the new standard.’ However, we are not COPD scene to gain approval, having won be competing for shares of this patient quite there yet.” over EU regulators in July this year. population in Europe. Dansey concluded by saying that “late- The third late-phase triple COPD combi- The CHMP highlighted that the ben- stage development used to be an orga- nation in the pipeline is AstraZeneca PLC’s efits of Trelegy Ellipta, which is indicated nized activity – Phase I, Phase II, relapse PT010 (budesonide/glycopyrronium/for- as a maintenance treatment, are its abil- Phase III, front-line Phase III, adjuvant Phase moterol). This product is currently in Phase ity to improve lung function compared III – a 10-15 year span. Now we are in three- III trials and AstraZeneca expects to make with budesonide/formoterol administered year cycles where everything is running at regulatory submissions in the US and Eu- twice-daily in moderate to severe patients once, in both the late-world and the early rope in 2019. not adequately controlled with corticoste- world of discovery. Everything is running in Trelegy Ellipta is a combination of an roid and long acting beta agonist. parallel without waiting for some sequential inhaled corticosteroid (ICS), a long-acting A final decision by the European Commis- outcome, but the reason is because the re- muscarinic antagonist (LAMA) and a long- sion on Trelegy Ellipta’s approval is expected sults are amazing.” acting beta2-adrenergic agonist (LABA), by the end of 2017. Published online 14 September 2017 delivered once daily in GSK’s Ellipta dry Published online 15 September 2017 scrip.pharmamedtechbi.com 22 September 2017 | Scrip | 7 ESMO

New Melanoma Frontier Opens To Bristol’s Opdivo And Novartis/Glaxo’s BRAF/MEK Combo EMILY HAYES [email protected]

he battle for primacy in melanoma setting. Interferon has been a controversial ondary endpoint, are not mature, but cross- treatment is likely to move to the treatment for this line of therapy in the US over from the Yervoy arm is allowed after re- T early, adjuvant (post-surgical) set- and is not accepted in Europe. The FDA’s lapse, which could complicate that measure. ting, following the release of strong data for October 2015 approval of Bristol’s CTLA-4 Importantly, Opdivo was very well toler- Bristol-Myers Squibb Co.’s immunothera- inhibitor Yervoy (ipilimumab) for the adju- ated compared to Yervoy – the rate of Grade py Opdivo and Novartis AG/GlaxoSmith- vant treatment of melanoma was ground- 3/4 adverse events and dropouts were 14% Kline PLC’s BRAF and MEK inhibitors Tafinlar breaking, but the drug is highly toxic. vs. 46% and 10% vs. 43%, respectively. The and Mekinist, based on full Phase III results In the US, where Yervoy is approved for ad- most common severe events for Opdivo presented at the European Society of Medi- juvant use and provided by the company for were fatigue (0.4%), diarrhea (1.5%) and rash cal Oncology (ESMO) annual meeting. free, Bristol says that from 55% to 60% of ad- (1.1%). There were two deaths in the Yervoy Bristol’s PD-1 inhibitor Opdivo and No- juvant melanoma patients get treatment and arm and none for Opdivo. vartis/Glaxo’s Tafinlar (dabrafenib)/Mekinist of those two-thirds get the company’s drug. Yervoy had been compared to placebo in (trametinib) combination both dramati- However, anecdotal accounts suggest a pivotal adjuvant melanoma study, so the cally and significantly increased relapse-free that patients have been wrestling with Yer- results can be extrapolated to show that survival (RFS) rates and were well-tolerated voy as an option – terrified of their disease Opdivo “is far better than no adjuvant treat- in two trials in the adjuvant treatment of coming back, but also terrified of experienc- ment for high risk melanoma,” investigator melanoma for patients at high risk of re- ing bad side effects when their disease is in Jeffrey Weber, deputy director of the Perl- currence – CheckMate 238 and COMBI-AD, remission, commented Tim Turnham, a con- mutter Cancer Center in New York, said in respectively. Conversely, Roche’s BRAF/MEK sultant at New York-based Mark Krueger & an ESMO statement about the data. combo Zelboraf (vemurafenib) and Cotellic Associates and former executive director of “Nivolumab looks like a superior adjuvant (cobimetinib) missed the primary disease- the Melanoma Research Foundation. melanoma regimen compared to ipilim- free survival (DFS) endpoint in the BRIM8 Opdivo is far more tolerable than Yervoy umab from every angle. It leads to better adjuvant melanoma study. and has always been viewed as a better bet relapse-free survival, has fewer side effects, All three studies were presented on Sept. for earlier lines of treatment. Observation has and is well tolerated,” Weber said. 11 at the ESMO meeting in Madrid. The been the standard of care in the adjuvant set- Merck’s competing PD-1 inhibitor Key- CheckMate 238 and COMBI-AD trials also ting – though that could change now that truda also is being studied in adjuvant mela- were fully detailed in the New England Jour- there are two different therapies with brand noma (Stage IIIa, IIIb and IIIc) in the Phase nal of Medicine (NEJM) the same day. new data showing they are really effective in III KEYNOTE-054 study, though it is being Novartis plans to file its combination in adjuvant setting, Turnham told Scrip. tested against placebo. This study also has a adjuvant melanoma in the fourth quarter New data presented at the ESMO meet- relapse-free survival endpoint. The primary while Bristol was less specific about its filing and reported the same day in the NEJM completion date is May 2018. ing plans, nothing that it looks “forward are likely to move the old immunotherapy/ John Haanen, professor of oncology at to working with regulatory authorities to targeted treatment rivalry into the adjuvant the Netherlands Cancer Institute, said in the make Opdivo available to adjuvant mela- setting and create new debates about what statement issued by ESMO that if “relapse- noma patients.” patients should get when they relapse after free survival is better with pembrolizumab, it adjuvant treatment. is likely that adjuvant anti-PD-1 will become A STEP BACK TO STEP FORWARD Bristol’s CheckMate 238 study tested standard of care for high-risk melanoma in PD-1 inhibitors – Bristol’s Opdivo and Merck Opdivo versus Yervoy in 906 patients with the near future, provided an overall survival & Co. Inc.’s Keytruda (pembrolizumab) – are surgically-resected Stage IIIb/c and IV mela- benefit is also shown.” approved for all lines of therapy in meta- noma and with at least a 50% risk of relapse In its statement about the data, Bristol static (Stage IV) melanoma. The BRAF/MEK in five years. The primary endpoint was stressed that “Opdivo is the first anti-PD-1 combinations are approved for all lines of relapse-free survival with overall survival as to improve RFS and the only I-O therapy to therapy for metastatic melanoma patients a secondary measure. Top-line results were demonstrate superiority versus an active with BRAF mutations – about half of the reported in July. control in this patient population.” population. However, there has long been Researchers reported that the relapse-free a debate about whether patients with BRAF survival rate at 12 months was 70.5% for Op- BRAF/MEK COMBO MOVES mutations should get a BRAF/MEK combo divo vs. 60.8% for Yervoy (HR=0.65). Results IN LOCKSTEP or immunotherapy upfront. were consistent across subgroups, including Although the BRAF/MEK combos have a All of the sponsors also have been looking good performance in patients with BRAF different mechanism, they have competed to move into the earlier adjuvant (Stage III) mutations. Data for overall survival, a sec- with immunotherapy to be chosen as the

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first line of therapy in the BRAF-positive set- pre-specified interim analysis boundary of Toxicity profiles will factor into these deci- ting. The debate has always come down to P=0.000019,” COMBI-AD investigators noted. sions. The most common severe side effects sequencing – whether patients are better The data show that most patients (77%) in the COMBI-AD study were fever (5%), chills off getting targeted treatment or immu- with no treatment survive and it will be in- (1%) and fatigue (4%). Rates of cutaneous notherapy at the start – as opposed to an teresting to see how this plays out over time squamous cell carcinoma were similar (2%) as either/or choice. with longer follow-up, Turnham said. were basal-cell carcinoma (4% versus 3%) and The COMBI-AD study tested Tafinlar/Me- Hauschild, who is professor of dermatol- non-cutaneous cancers (2% versus 1%). One kinist against placebo in 870 patients with ogy, at the University of Kiel in Germany, de- fatal serious adverse event (pneumonia) was BRAFV600E and V600K mutations. Patients scribed the COMBI-AD data as “the best re- reported in the combination-therapy arm. were treated for 12 months, with relapse- sults ever shown” for an adjuvant treatment Turnham said the safety profile looks very free survival as the primary endpoint. in Stage III melanoma. good. The BRAF/MEK combination also has The combination significantly reduced Efficacy came at the cost of more side ef- the advantage of being oral whereas PD-1 the risk of relapse by 53% (58% RFS versus fects relative to placebo, but the investigators inhibitors are given by infusion, but it may 39% for placebo at the estimated three- noted that there were no new toxicities com- be less familiar to oncologists in the com- year mark), with consistent results across pared to what has been reported for Stage munity setting, whereas checkpoint inhibi- subgroups, researchers reported. Interferon, IV disease and concluded that overall the tors are in routine use for other types of can- by comparison, was previously shown to combo treatment was well-tolerated. In the cers, he said. reduce risk by 20% compared to placebo, study, the rate of Grade 3/4 adverse events COMBI-AD investigator Axel Hauschild not- and dropouts for the combination relative to ROCHE COMBO MISSES MARK ed in a statement about the data. placebo were 41% versus 14% and 26% ver- The COMBI-AD results give another advan- “The estimated rates of relapse-free sur- sus 3%, respectively (see table below). tage to Tafinlar/Mekinist over Roche’s com- vival were 88% at one year, 67% at two years Olivier Michielin, head of Personalized An- peting Zelboraf/Cotellic combination. Zel- and 58% at three years in the combination alytical Oncology in Lausanne, Switzerland boraf was the first BRAF inhibitor approved, therapy group, as compared with rates of and ESMO Melanoma Faculty Coordinator but Glaxo’s Tafinlar/Mekinist was the first ap- 56%, 44% and 39%, respectively, in the pla- said in ESMO’s statement that the data were proved combination.) cebo group,” University of Sydney’s Georgina “practice-changing.” In the BRIM8 adjuvant study of 498 BRAF- Long and colleagues reported in the NEJM. “Both ipilimumab and the combination of mutant patients, Zelboraf/Cotellic failed to The overall survival data also were promis- dabrafenib plus trametinib have improved significantly improve disease-free survival ing. “The 3-year overall survival rate was 86% overall survival compared to placebo. We (DFS) in Stage IIIc melanoma, though the in the combination-therapy group and 77% now need to determine which adjuvant combination did improve DFS in resected in the placebo group (hazard ratio for death, strategy is best suited for which patient, fac- Stage IIc-IIIb patients, reducing risk of recur- 0.57; 95% CI, 0.42 to 0.79; P=0.0006), but toring in also the upcoming results of PD-1 rence by 46% (see table below). this level of improvement did not cross the blockade in that setting,” Michielin said. Published online 11 September 2017

ESMO: Comparison Of Results From Phase III Trials In Adjuvant Melanoma SPONSOR/PRODUCT/TRIAL DESIGN KEY EFFICACY RESULTS KEY SAFETY FINDINGS Opdivo at 3 mg/kg by IV every two Opdivo reduced risk of recurrence Bristol’s PD-1 inhibitor Opdivo, weeks or Yervoy 10 mg/kg every by 35% vs Yervoy at 12 months Lower rate of treatment-related, CheckMate 238 (n=906): Patients three weeks for four doses and (HR 0.65; 97.56% CI: 0.51 to 0.83; Grade 3/4 side effects and drop- who have undergone complete every 12 weeks starting at week 24. p<0.0001). The 18-month RFS rates outs for Opdivo compared with resection of Stage IIIb/c or Stage IV Treatment until relapse, unaccepta- were 66.4% for Opdivo and 52.7% Yervoy (14% vs. 46% and 10% vs. melanoma. ble toxicity or withdrawal for up to for Yervoy. Efficacy consistent 43%, respectively). one year. Primary endpoint: RFS. across all subgroups. With median follow-up of 2.8 years, combo significantly reduced the Novartis/Glaxo’s Tafinlar/Mekinist Tafinlar/Mekinist vs. placebo. Treat- Grade 3/4 event and dropout rates risk of relapse or death by 53% BRAF/ MEK combo, COMBI-AD ment for 12 months with median higher for combo compared with compared to placebo (HR, 0.47; CI (n=870): Completely resected, follow-up of 2.8 years. Primary placebo (41% vs. 14% and 26% vs. 0.39–0.58). Benefit across all sub- BRAF+, Stage III melanoma. endpoint: RFS. 3%, respectively). groups. Also significantly improved OS, secondary endpoint. Primary endpoint: DFS. Two co- Study did not meet its primary Roche’s Zelboraf/Cotellic BRAF/ horts, hierarchical analysis. Cohort endpoint of significantly reducing The safety profile was consistent MEK combo, BRIM8 (n=498): 1: Stage IIc, IIIa or IIIb. Cohort 2: the risk of recurrence in Stage IIIc with previous studies of Zelboraf in Completely resected BRAF+ Stage Stage IIIc. Cohort 2 had to meet melanoma (Cohort 2). Significant advanced melanoma. IIb-IIIc melanoma. primary endpoint before Cohort 1 46% reduction in recurrence risk in analysis. Cohort 1 in informal analysis. Source: ESMO and company statements.

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Clovis CEO Sees Rosy Future With Rubraca KEVIN GROGAN [email protected]

aving presented a strong full set of data on its PARP inhibitor Rubraca (rucaparib), Clovis Oncology Inc. once again is Hbeing mentioned as an attractive candidate to be acquired, but its chief executive Patrick Mahaffy is not listening to the rumors. “Takeover target? I haven’t heard this. Really?” he smiled in an interview with Scrip at the European Society for Medical Oncology congress in Madrid. When pushed on whether he has been approached, Mahaffy responded by saying that “everyone in this industry has dialogue all the time, whether that is an approach or just dialogue is maybe semantics.” However, he did say that “we’ve never put up a ‘for sale’ sign and we never will. I think companies can be acquired but not sold well, sounds like putting your house up for sale. We are going to run this until or if someone shows up. My view is pretty simple, I get paid to work for the shareholders and if someone comes forward with a big enough number, I would go to them and say ‘vote and decide’.” Mahaffy added that “I have done this in my career twice so I’m Productions Atstock Shutterstock: pretty aware how this is done.” He was previously CEO at Pharmion Clovis CEO Mahaffy: We have never put up a ‘for sale’ sign and never will Corp, which he founded in 2000 and sold to Celgene Corp. in 2008, and before than, from 1992 through 1998, CEO of NeXagen and its Mahaffy also spoke with much enthusiasm about the clinical col- successor, NeXstar Pharmaceuticals Inc., which was acquired by laboration signed in July with Bristol-Myers Squibb Co. to partner Gilead Sciences Inc. in 1999. Rubraca with the anti-PD-1 blockbuster Opdivo (nivolumab). The He told Scrip that “all teasing aside, I think about this far less than combo will be tested in Phase III studies in first-line maintenance of anyone else does. I think I’m supposed to drive the company and ovarian cancer (beginning by the end of this year) and triple-nega- until somebody shows up, I’m going to create additional value.” tive breast cancer (around the end of this year), as well as a Phase II That value will come from Rubraca, for which full data from the study in metastatic, castration-resistant prostate cancer. ARIEL3 trial in advanced ovarian cancer were presented at ESMO. They “It’s a shared commitment to the combination and a relatively equiv- showed that maintenance therapy with the drug improved progres- alent sharing of the cost,” he told Scrip, which for a small company “dra- sion-free survival in each of the three populations studied - women matically expands our clinical reach as we are not solely responsible for with BRCA or HRD mutations or all-comers (those with neither). study costs.” Mahaffy said the respective research teams have bonded ARIEL3 demonstrated 13.7 months of median PFS in the all-com- well, hence the speedy start for the late-stage trials, “adding that the ers population in the trial for Rubraca compared with 5.3 months PARP/PD-1 combination will hopefully mean that treatment can go for those on placebo. Principal investigator Jonathan Ledermann at earlier and broader and be a big part of our development portfolio.” University College London noted that it is also clinically significant The Clovis CEO also spoke of plans to build up the company’s that Rubraca not only sustained patients’ most recent response to European operations. Rubraca was filed during the fourth quarter of platinum, but in some also enhanced that response, including the 2016, so action is expected by the end of this year or the beginning radiological elimination of residual tumor. of 2018. On approval, the ARIEL3 finding will be submitted for the Rubraca was given the green light by the US FDA in December maintenance treatment indication and to get an expansion label will 2016 as third-line therapy for women with the BRCA mutation. It will take about another six months. now file the ARIEL3 data with the agency by October so the drug Clovis will market Rubraca on its own and already has in place a can get approval as second-line or later maintenance treatment in- European leadership and market access team, as well as a medical dication in ovarian cancer, expanding the number of patients four affairs group. A field force will be set up, rather than using a contract or fivefold. sales organization, “as the motivations and desires are greater when If approved, it means that Rubraca will be able to play on a level play- it’s your own.” ing field with the two rival PARP inhibitors that have already got the FDA Mahaffy added that in Europe “the ever-present pressures on reim- thumbs-up for ovarian cancer maintenance therapy – AstraZeneca bursement have increased” and he called for an open dialogue about PLC’s Lynparza (olaparib) and Tesaro Inc.’s Zejula (niraparib). Analysts access to innovative medicines: “just driving prices down, down, are finding it hard to separate the three and Mahaffy said that while it down will just stifle innovation.” Clovis is already in talks in England was too early to say Rubraca is best in class, “I don’t think there is any evi- and Wales with the National Institute for Health and Care Excellence dence that any PARP inhibitor is any better and we have perhaps found (NICE) on Rubraca and Mahaffy hopes the agency will improve ac- that really good combination of acceptable tolerability and good clini- cess to new oncology therapies – if not, it could face “a revolt” from cal activity that will appeal to physicians.” He also added that the hazard society “against it becoming a second-world country.” ratios in ARIEL3 “are superb and marginally better than the others.” Published online 12 September 2017

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Lilly’s Abemaciclib On Par With Ibrance In Breast Cancer, But Not ‘Clearly Superior’ LUCIE ELLIS [email protected]

t is unclear how much commercial traction warning on abemaciclib’s label. “In that sce- Eli Lilly & Co. will get with incoming breast nario, it is possible that competitors could Icancer therapy abemaciclib, analysts from counter-detail LLY’s label,” he said. Lilly high- Bernstein said after the big pharma present- lighted, when presenting the Phase III data ed Phase III data from the MONARCH-3 trial at ESMO, that patients who experience VTE at the European Society for Medical Oncol- did not discontinue the trial and were able ogy’s annual meeting in Madrid. to continue treatment with abemaciclib. “The presentation of full MONARCH-3 results will largely support investors’ disbe- OTHER LIMITING SIDE EFFECTS lief that abemaciclib will be clearly superior Meanwhile, analysts from BMO Capital Mar-

[to market leading drugs], despite LLY con- Cheryl Quigley Ann Shutterstock: kets believe that the higher rate of diarrhea tinuing to put its best face forward,” Bern- Lilly’s Abemaciclib will face seen in patients treated with abemaciclib stein analysts said in a Sept. 10 note. could limit its adoption by physicians, if the Overall response rate for abemaciclib was off with Pfizer’s Ibrance if drug is approved by regulators next year. 59.2% compared to 43.8% for placebo in the “We believe that the higher rate of grade MONARCH-3 study This is only slightly high- approved in 2018 3/4 diarrhea with abemaciclib… coupled er than data for market leading therapies, with the twice daily continuous regimen, Pfizer Inc.’s Ibrance (10.9%) and Novartis could limit abemaciclib’s uptake, particularly AG’s Kisqali (13.8%). Abemaciclib’s progres- to both Ibrance and Kisqali on side-by-side given that Ibrance is remarkably well estab- sion free survival hazard ratio was 0.543, analyses. These safety data were in line lished,” BMO analysts said. which is not meaningfully different from with expectations. Still, BMO analysts expect approval of abe- Ibrance’s 0.58 and Kisqali’s 0.568. Median PFS However, patients in the study treated with maciclib in 2018 and peak sales of $3.2bn. for abemaciclib in MONARCH-3 has not yet Lilly’s drug saw a higher rate of venous throm- However, they now see downside risk after been reached. boembolic events (VTE) (n=16; or 4.9%) com- ESMO. “ It will be challenging for abemaci- Abemaciclib, Ibrance (palbociclib) and pared to placebo (n=1; or 0.6%). An outcome clib to gain meaningful share from Ibrance,” Kisqali (ribociclib) are all cyclin-dependent investors had not been anticipating. BMO experts said. kinase 4/6 inhibitors. Bernstein analysts highlighted that an Deutsche Bank analysts also anticipate a While Bernstein analysts have qualms imbalance in deaths was also noted in the 2018 launch for abemaciclib, but the group over abemaciclib’s ability to compete MONARCH-3 trial; 2.4% for abemaciclib has forecast peak sales of around $2bn – against Ibrance, experts at Jefferies were versus 1.2% for placebo. Two of the deaths roughly one-third of its estimate for Ibrance, more upbeat. within the abemaciclib arm were due to which was approved in the US for breast Abemaciclib’s PFS hazard ratio did not embolism, but no deaths in the placebo cancer in 2015. quite meet the threshold of ≤0.52 Jefferies arm were linked to this cause. Despite Deutsche Bank analysts not ex- analysts had set for “clear superiority” over A warning for VTE was initially placed on pecting abemaciclib to out-perform Pfizer’s Ibrance. “However, we note that median PFS the label for Ibrance when Pfizer’s drug was drug, they do believe the MONARCH stud- was not yet reached in the abemaciclib arm first approved in the US but this was sub- ies have demonstrated a clinical profile for and therefore may still fall below 0.52 when sequently removed; furthermore, VTE is an abemaciclib that could be competitive further updates of the data are presented adverse event associated with breast can- within the rest of the CDK 4/6 class. during H1’18,” they said. cer in general. Lilly has previously reported data from “We conclude that abemaciclib likely Bernstein analyst said they “were not the Phase II MONARCH-1 trial, which is beats Ibrance on efficacy,” Jefferies analysts expecting materially better efficacy versus testing abemaciclib as a monotherapy in added. MONARCH-3 is a randomized, dou- competitors, and we expected a higher patients with HR+/HER2- breast cancer, ble blind trial of abemaciclib in combination rate of diarrhea” in the MONARCH-3 trial. after chemotherapy for advanced disease; with an aromatase inhibitor versus placebo However, the VTE finding “lessens our and the MONARCH-2 study that is com- as initial therapy in postmenopausal wom- confidence in our forecasts and could put paring the efficacy and safety of abemaci- en with hormone receptor positive, HER2 them [Lilly] at risk, depending on how reg- clib plus fulvestrant with fulvestrant alone negative advanced breast cancer. ulatory agencies react.” in patients with advanced breast cancer. During MONARCH-3, abemaciclib treat- Umer Raffat, a senior analyst at Evercore It will be challenging for abemaciclib to ed patients saw a higher rate of diarrhea ISI, said in a Sept. 10 note that the VTE safety gain meaningful share from Ibrance. but a lower rate of neutropenia, compared concerns from MONARCH-3 could lead to a Published online 11 September 2017

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CONTINUED FROM COVER nounced 7,000 job cuts since acquiring the and with a clear strategic direction.” He is a particularly large problem for Teva as Allergan generics. Within three months of added: “The board is very pleased with the biggest player – more than half of its his arrival at the smaller Lundbeck, Schultz the strategic path and the outlook for revenues coming from generic medicines announced a restructuring with 1,000 the company and sees no reason to sold in the US – and will present a different job cuts. (Also see “Lundbeck Restructures change the strategic path the company type of challenge for Schultz, who is more Around 5 Key Products; 1,000 Jobs To Go” has entered.” accustomed to positioning a business to Scrip, 19 Aug, 2015.) For his part, Schultz said he had been weather generic erosion of formerly patent- In May, Teva revealed plans to divest its “extremely happy” as CEO of Lundbeck, protected products. women’s health portfolio and its oncology which was on track to “deliver the best fi- Teva has riled investors by failing to meet and pain businesses in Europe as it scram- nancial result ever” in 2017. “The outlook guidance on several occasions, and the bled to meet a $5bn debt reduction target is strong with high profitability and solid company lowered its guidance for the year by the end of 2017. It remains to be seen cash flow generation many years ahead following a disappointing second quarter; how much progress will be made with this and I could easily see myself working at management also said Teva would cut its before Schultz joins; for the time being he Lundbeck for many years. I just got an of- dividend by 75%. (Also see “Teva SOS: Trou- fer that I couldn’t refuse, being CEO at one bled Drug Maker Seeks Audacious Captain To of the biggest pharmaceutical companies Take The Wheel” Scrip, 3 Aug, 2017.) ‘I could easily in the world,” he was quoted as saying in Schultz’s inexperience in generics left Lundbeck’s press release. Divan wondering “how his appointment see myself working However, the two-year surge in Lund- may impact Teva’s long-term strategy in that at Lundbeck for beck’s share price have left some fearing business given the structural challenges the that the company may be over-valued. generics industry is currently facing.” many years … I just Deutsche Bank analysts wrote in a Jul. 28 Still, Schultz has risen to other challenges note that “following a 30% share price in- in his career, which included experience got an offer that I crease year-to-date, the shares are now working in the pharmaceutical and health trading at 30x 2017e earnings … reflect- care sector for McKinsey and Anderson Con- couldn’t refuse’ ing a very positive scenario for the com- sulting, implementing a metrics focused pany’s new drugs, equivalent to Rexulti approach to operations at Novo Nordisk, [the depression/anxiety/psychosis drug modernizing that firm’s large-scale biologics remains at Lundbeck and no firm start date brexpiprazole] generating $3bn of peak production and leading its expansion into has been announced. Teva also will need global revenue.” Chinese and US markets. to secure a permanent CFO – a role that’s The analysts described this scenario Teva has faced some criticism from in- been filled by interim CFO Michael McClel- as “a significant leap of faith” given that vestors for paying too much to acquire the lan since July, following the departure of Deutsche Bank is forecasting peak sales for large generics portfolio from Allergan PLC Eyal Desheh. the product of around $1.9bn. They said last year given the challenges in the US, “management has progressed the pipeline but consolidation is one of the ways Teva LUNDBECK UNDER PRESSURE and weathered patent headwinds well” but sought to overcome the challenges. For Lundbeck, whose share price fell 13.8% warned “we now believe there is a level of Interim CEO Peterburg emphasized that on Sept. 11 after Schultz’s departure was an- exuberance that ignores the fact that Lun- the firm is on course to generate at least nounced, Teva’s news is not the only blow. dbeck is a company with small molecule $2bn from the sale of non-core assets. The The company also announced that chief (easy to copy at patent expiry) products company already has begun “optimizing our commercial officer Staffan Schüberg re- with a limited pipeline.” operations and geographic footprint” and signed. It described the double resignation Both Lundbeck executives will remain in focusing resources on assets (both generic as a coincidence, and noted that Schüberg their positions until further notice, and the and specialty drugs) that offer the best re- was leaving to become CEO of a privately board will immediately begin the search for turns on investment. owned company. their replacements. Schultz eventually will Schultz’s arrival could accelerate that Lundbeck’s chair Lars Rasmussen said relocate to Israel to be based at Teva’s Petah rationalization and may well herald more in a statement that Schultz was leaving Tikva headquarters. job losses, although Teva already has an- the firm when it was “strong and healthy, Published online 11 September 2017

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With J&J’s Departure From HCV, Gilead Stands Alone In ‘Nuc’ Field JOSEPH HAAS [email protected]

buvir – which is approved for solo use as Sovaldi and is the backbone of the combination products Harvoni, Epclusa and Vosevi. Earlier this year, Gilead de-emphasized hepatitis C, both reducing sales guidance for its drugs and saying that its therapeutic focus going forward would be on HIV, oncology and other areas. This came after the company reported a 35% global reduction in HCV sales during the fourth quarter compared to 12 months earlier. Gilead then took a major step forward in oncology in late August with an $11.9bn purchase of CAR-T therapy-focused biotech Kite Pharma Inc. Technically, the only remaining nuc in clinical development for HCV is Merck’s uprifosbuvir (MK-3682), deployed in Phase II studies as part of three- or four-drug combination regimens. But Merck significantly reduced expectations for that compound in February, when it revealed it would take a $2.9bn pre-tax intangible asset im- Shutterstock: Lightspring Shutterstock: pairment charge after assessing the competition in the HCV space.

nd then there was one. Merck & Co. Inc. de-emphasized J&J’s decision effectively cements Gilead as development of its experimental nucleoside polymerase the only HCV company with a nucleoside Ainhibitor for hepatitis C earlier this year, so with Johnson & Johnson’s Sept. 11 decision to exit HCV drug development, the polymerase inhibitor in its portfolio, evading last “nuc” that could have provided competition to Gilead Sciences Inc.’s sofosbuvir-driven dominance likely has reached a standstill. another potential threat to its dominance Despite promising Phase II data indicating potential for a six-week anchored by sofosbuvir duration of treatment with a three-drug combination that included the nuc AL-335, J&J said it will move away from HCV drug development due to the efficacy of what’s already available to patients. With the pharma’s announcement on Sept. 11 comes termination of its This is just the latest wave of companies to back away from the collaboration with Achillion Pharmaceuticals Inc., which contrib- HCV market due to the improved treatment landscape. Bristol- uted the NS5A inhibitor odalasvir to J&J’s three-drug combo. Myers Squibb Co. read the tea leaves earlier and gradually refo- The now-abandoned JNJ-4178 comprised AL-335, odalasvir and cused its virology investments as the HCV market developed. J&J’s protease inhibitor Olysio (simeprevir), which was approved by Achillion issued a statement on Sept. 11 saying it received notice the US FDA in 2013. J&J picked up AL-335 in a $1.75bn buyout of of J&J’s decision, including the termination of the partnership around Alios BioPharma Inc. in 2014. odalasvir signed in May 2015, two days earlier. CEO Milind Desh- The trio produced a 100% sustained virologic response (SVR) in 20 pande said he was disappointed by the decision, because he felt HCV patients treated for six weeks in Phase IIa data reported last Sep- patients could benefit from the convenient, short-duration therapy tember. (Also see “J&J, Achillion Could Set Six-Week Treatment Para- JNJ-4178 might have offered to patients. digm In HCV” Scrip, 9 Sep, 2016.) J&J said after unveiling those data At present, the shortest duration of HCV treatment included in la- that it would initiate a Phase IIb trial with the regimen in treatment- beling for any approved therapy is eight weeks, which represents a naïve and treatment-experienced, non-cirrhotic patients of all HCV significant improvement from the standard of 48 weeks just six years genotypes except genotype 3. ago. Harvoni (sofosbuvir/ledipasvir) and AbbVie Inc.’s second-gen- Now, the pharma says it will complete all ongoing Phase II stud- eration combination therapy for HCV, Mavyret (glecaprevir/pibren- ies of the combo, but will undertake “no additional development tasvir), approved by the FDA on Aug. 3, both have labeling recom- thereafter.” In virology, J&J intends to focus exclusively on developing mending an eight-week treatment duration for some patients. a functional cure for hepatitis B, Lawrence Blatt, global therapeutic Stockholm-based Medivir AB also issued a statement on J&J’s area head for infectious disease therapeutics, said in a statement. decision to exit HCV development, saying that the change would not affect its existing licensing agreement with the pharma for STRONG STANDING FOR GILEAD simeprevir. Medivir remains entitled to royalties on global sales of J&J’s decision effectively cements Gilead as the only HCV company Olysio monotherapy, although revenues from that product have with a nucleoside polymerase inhibitor in its portfolio, evading an- declined substantially since peaking at about $2.3bn in 2014. other potential threat to its dominance anchored by the nuc sofos- Published online 11 September 2017 scrip.pharmamedtechbi.com 22 September 2017 | Scrip | 13 HEADLINE NEWS

Boehringer Taps Gubra For Early- Teva’s US IUD Brings In $1.1bn Stage Obesity Deal Although the strategy may change LUBNA AHMED [email protected] when Kare Schultz, the newly appointed president and CEO at Teva Phar- dding to its already busy metabolic “We have several research programs in maceutical Industries Ltd. settles disease portfolio, Boehringer In- obesity, diabetes, NASH and GI and are con- in, the company’s first divestment of Agelheim GMBH has sealed a col- tinuously looking to attract the right part- a non-core women’s health asset, the laboration and license agreement with Den- ners, with the right capabilities, to work with intrauterine copper-releasing device, mark-based Gubra ApS to develop peptide us in getting these programs towards the Paragard, was announced on Sept. 11. compounds for obesity. Gubra stands to re- clinic,” Blou said. The IUD and its Buffalo, NY based ceive up to €250m in upfront and success- manufacturing facility is to be sold to based development and commercialization BI METABOLIC PROFILE the US-based CooperSurgical Inc. for milestone payments, although details of the According to a report by Datamoni- $1.1bn in cash, a tidy sum that Teva says split between upfront payments and mile- tor Healthcare (DMHC) from May 2017, will be used to repay term loan debt un- stones were not disclosed. though the lack of pipeline launches will der its senior credit facility. Paragard is an cause a slump in the German group’s IUD that is sold only in the US, and can Boehringer adds obesity piece sales over 2016 to 2026, Boehringer’s prevent pregnancy for up to 10 years, and to diabetes offering metabolic portfolio and expansion in on- had revenues of $168m in the 12 months cology will drive its near-term growth. ending June 30, 2017. The acquisition is A large portion of sales is expected to expected to close before the end of 2017, come from Boehringer/Eli Lilly & Co.’s dia- after satisfying usual conditions that betes alliance, which DMHC forecasts will include antitrust clearance in the US. grow strongly, bringing BI $3.9bn in rev- The sale will go some way to meet enues in 2026. Products under this alliance Teva’s strategy of paying down $5bn in include: the Tradjenta/Ondero (linagliptin) debt by the end of 2017, as the Israel- franchise, which was launched in the US in headquartered generics company takes

Shutterstock: kenary820 Shutterstock: 2011 for type 2 diabetes as a long-acting measures to reduce its multi-billion dol- DPP-IV inhibitor; Jardiance (empagliflozin), lar debt pile. The intention to divest its Boehringer has various candidates in late the sodium-glucose cotransporter-2 (SGLT- global women’s health business and its preclinical and early clinical stages that it be- 2) inhibitor approved by the FDA and EMA European oncology and pain businesses lieves address the high therapeutic need in in 2014 for type 2 diabetes; and a biosimilar were announced by Teva in May 2017. obesity, which a spokesperson described as of Sanofi’s Lantus (insulin glargine) Basa- Teva’s desire to sell has reportedly an “underlying factor for many other devas- glar/Abasria (insulin glargine). been matched by widespread interest tating diseases.” Those in the diabetes space are ex- from potential buyers that have includ- Boehringer, which has worked with Gu- panding their roots from focusing solely ed private equity, and generic players bra on metabolic diseases previously, said on diabetes to conditions like cardiovas- from the US, Europe and India. that its partner had “expertise in the devel- cular disease and obesity. For example, The company said on Sept. 11 it opment of peptidic compounds and could the FDA and CHMP approved the expan- would continue to pursue additional offer a novel approach that ideally comple- sion of Jardiance’s label in Dec. 2016 and divestment opportunities, including the ments current parts of our portfolio.” Jan. 2017 to include the drug’s ability to sale of remaining products in its global Gubra, a preclinical contract research orga- reduce the risk of cardiovascular mortal- women’s health business, and its oncol- nization that is also developing in-house pro- ity in type 2 diabetes patients at risk of CV ogy and pain businesses in Europe. It grams for partnering, is active in the metabol- events – Jardiance being the first SGLT-2 expects to generate at least $2bn in total ic space with a particular focus on preclinical to demonstrate such positives outcomes. proceeds from the sale of these busi- research in diabetes, obesity, nonalcoholic Novo Nordisk AS’s Saxenda (lira- nesses, as well as additional asset sales steatohepatitis (NASH) and gastrointestinal- glutide) is another example of such an made by the end of 2017. On the same related (GI) diseases. It recently concluded expansion. The drug was originally de- day it announced the appointment of a four-year long collaboration with Sanofi, veloped for diabetes as Victoza, but fol- Schultz as its new president and CEO. which met all three of its undisclosed preclin- lowing evidence showing it caused sig- Teva said in May this year that the ical milestones and successfully discovered nificant weight loss, Novo decided to European oncology business didn’t have GI peptides for the treatment of diabetes and pursue its potential in obesity. The prod- enough in its pipeline, but it wanted obesity. CEO Henrik Bloutold Scrip that the uct was later approved for obesity in the to keep its US oncology business that company was on the hunt for potential part- US in 2014 and EU in 2015. included Treanda (bendamustine). ners for its ongoing research programs. Published online 11 September 2017 [email protected] 12 Sept 2017

14 | Scrip | 22 September 2017 © Informa UK Ltd 2017 CLINICAL TRIAL

Sanofi And Regeneron Hit Asthma Phase III Endpoints With Dupixent ALEX SHIMMINGS [email protected]

anofi and Regeneron Pharmaceu- It was also more effective in patients At 12 weeks, there was a mean improve-

ticals Inc.’s novel therapy Dupixent with higher baseline eosinophil counts, ment in FEV1 of 210 mL (11%) in patients S(dupilumab) has hit both primary end- which are generally thought to be asso- with 150 eosinophilic cells/µL or greater, points in a Phase III trial in asthma, showing ciated with poorer asthma control and and 240 mL (18%) in patients with 300 eo- a greater benefit in those with the most al- higher rates of exacerbations. The compa- sinophilic cells/µL or greater (p<0.001 for lergic form of the disease and setting the nies say this lends credence to their belief all groups). stage for a US FDA filing to expand its indi- that the IL4/IL13 pathway targeted by the The overall rates of adverse events, cations by the end of the year. monoclonal antibody product is a critical deaths, infections, conjunctivitis, herpes The product – which was approved in driver of allergic disease. and discontinuations were comparable be- March by the FDA for the treatment of mod- QUEST enrolled 1,902 patients including tween the drug and placebo groups. Injec- erate-to-severe atopic dermatitis in adult 107 adolescents and compared 200 mg of tion site reactions were more common with patients whose disease is not adequately dupilumab every other week with a loading dupilumab groups at 17% compared with controlled with topical prescription therapy dose of 400 mg, 300 mg every other week 8% for placebo. or when therapies are not advisable – has with a loading dose of 600 mg, with two The Leerink analysts said that on the been tipped as a potential blockbuster and separate placebo groups. All patients con- surface, dupilumab’s 46% reduction its early market performance is being close- tinued on a medium or high dose inhaled in exacerbations for the intent to treat ly watched. It recorded global sales of $29m corticosteroid (ICS) and up to two additional population (ITT) compares similarly to in the second quarter when some analysts controller medicines. the anti-IL-5 labels: Nucala produced a raised concerns that the atopic dermatitis The two primary endpoints of the 47-53% reduction and Cinqair a 41-50% market might not prove to be as lucrative study were the annualized rate of severe reduction. “However, the dupilumab trial as previously thought. (Also see “Regeneron exacerbation events at 52 weeks and the enrolled patients with any eosinophil And Sanofi Antibody Discovery Deal To End” absolute change from baseline in a stan- count, while the Nucala trial enrolled only Scrip, 4 Aug, 2017.) dard measure of lung function known as patients with blood eosinophils of greater The top-line success in a second major pre-bronchodilator forced expiratory vol- than or equal to 150 cells/µL at screening.

indication should shore up the product’s ume over one second (FEV1) at 12 weeks In the dupilumab trial’s subgroup analysis position, especially since at first glance (changes of 100 to 200 mL are considered of patients 150 cells/µL or greater, the ex- the data also suggest it might be better clinically relevant). acerbation reduction of 60% is superior to than its major rivals, the anti-IL-5 prod- The results for the 200 mg and 300 mg the IL-5 results of 41-53%.” ucts GlaxoSmithKline PLC’s Nucala (me- dupilumab dose groups were generally While the analysts believe the data are polizumab) and Teva Pharmaceutical comparable on both exacerbations and likely to produce a broad label for dupilum-

Industries Ltd.’s Cinqair (reslizumab). FEV1, and efficacy correlated with markers ab, they say the question is now whether Asthma is a more competitive market of allergic or atopic status such as blood other novel classes, such as AstraZeneca than atopic dermatitis but is substan- eosinophils. and Amgen’s anti-thymic stromal lympho- tially larger, say analysts at Leerink. They For the overall population, the 300 mg poietin (TSLP) antibody tezepelumab, will are forecasting revenue from the asthma dose reduced severe asthma attacks at show superior benefit in broad eosinophil indication of $137m in 2018, growing 52 weeks by 46%, and gave a mean im- count populations. rapidly to $2.7bn by 2020 and $4.1bn by provement in lung function at 12 weeks Amgen Inc. and AstraZeneca PLC re- 2022, assuming just a 4-5% penetration of of 130 mL (9%). cently released Phase II data for tezepelum- the poorly controlled asthma population The pre-specified primary analysis in- ab which they say could be a game changer. and comparable pricing to the atopic cluded hierarchical evaluation of these dermatitis indication. endpoints in patients with 150 eosinophilic OTHER DUPILUMAB STUDIES cells/µL or greater at baseline (about 70% of Data from the Phase III VENTURE study ex- QUEST patients), and in patients with 300 eosino- amining the ability of dupilumab to reduce Initial results show that the pivotal LIBERTY philic cells/ µL or greater (about 50%). oral corticosteroid use in patients with ASTHMA QUEST study of dupilumab in a At 52 weeks, in the 300 mg dose group, severe steroid-dependent asthma are ex- broad population of patients with uncon- dupilumab reduced severe asthma attacks pected later this year. Also included in the trolled, persistent asthma met its two pri- by 60% in patients with 150 eosinophilic LIBERTY ASTHMA clinical development mary endpoints: when added to standard cells/µL or greater, and 67% in patients with program is the TRAVERSE trial, a long-term therapies it reduced severe asthma attacks 300 eosinophilic cells/µL or greater (p<0.001 safety extension study. (exacerbations) and improved lung function. for all groups). Published online 11 September 2017

scrip.pharmamedtechbi.com 22 September 2017 | Scrip | 15 COMMERCIAL

Will Keytruda Price Differential Really Count In India? ANJU GHANGURDE [email protected]

erck & Co. Inc. has launched its breakthrough immuno- Scrip but gave no details, including on whether it may consider of- oncology therapy Keytruda (pembrolizumab) in India, put- fering equal monthly instalments [EMI]-based financing options for Mting the spotlight on the price tag that the PD-1 inhibitor Keytruda in the country. comes with in a predominantly out-of-pocket market. Merck said that as a global healthcare company, its role was first Merck did not share pricing details, other than to say that the prod- and foremost to discover and develop innovative medicines and uct comes with an ‘India-specific price’ – an oft-used position by for- vaccines that treat and prevent unmet medical needs. eign firms which typically denotes a significant discount to interna- “We also recognize that we have a role to play – in partnership with tional prices with an eye on affordability aspects in a largely self-pay other key stakeholders – in helping to ensure our products are acces- market like India. sible and affordable to those in need,” MSD India added. A report in the local media suggested that the maximum re- Innovator firms have long experimented with a tiered-pricing ap- tail price of one vial of Keytruda for a 21-day course is INR236,000 proach in India for costly patented medicines, while more recently ($3,685) compared with a reported US price of $12,500 per patient the trend of “drug financing” has also been tried and tested. Typically, per month, or $150,000 per year in 2014. The current US price posi- under such financing schemes, patients can stagger payment of the tion of Keytruda could not immediately be ascertained. actual therapy cost over a specified period via EMIs – along the lines An official with an Indian biopharma advisory firm told Scrip that of similar schemes for consumer durables. while KOLs were expected to endorse the product and patients who can afford the therapy will access the product in India, it is unlikely to INDIAN APPROVAL make a significant impact on Merck’s topline. Keytruda has been approved in in India for the treatment of unre- “KOLs will adopt it but not many patients may go for it mainly due sectable or metastatic melanoma – the product has been cleared for to the affordability aspect and insurance coverage is probably still multiple indications internationally. unclear,” the official said.Scrip could not immediately verify aspects A subject expert committee (SEC), an expert panel which advises around insurance coverage in India for Keytruda. the Indian drug regulator on trial-related approvals, had endorsed The official also drew parallels withRoche ’s Herceptin (trastu- Keytruda in November 2015, permitting a waiver of local clinical tri- zumab) in India some years back [prior to the launch of cut-price als, subject to certain conditions. Merck was granted permission to second brands], where physicians would prescribe the product import and market the drug in India in June 2016. only if they felt that the patient could afford it. (Also see “Biocon’s Last month the SEC (oncology and hematology) recommended cut-price biosim Herceptin: impact on patients and Roche in India” that MSD should conduct a Phase IV trial for Keytruda in at least 100 Scrip, 20 Jan, 2014.) subjects “as availability of patients is not a problem in India”. Health insurance penetration in India is estimated at about 25% Keytruda is approved by the US FDA for the treatment of certain of the population, with around 19% covered by government-spon- patients with metastatic melanoma, metastatic non-small cell lung sored health insurance schemes and the rest under private insur- cancer, recurrent or metastatic head and neck cancer, refractory clas- ance, according to a September 2015 Bank of America Merrill Lynch sical Hodgkin lymphoma, urothelial carcinoma and microsatellite in- research report. stability-high cancer. Studies of Keytruda – from the largest immuno- Leena Menghaney, a lawyer working on public health and access oncology program in the industry with more than 550 trials – include to medicines in India, told Scrip that there had been occasions when a wide variety of cancers and treatment settings. physicians did not inform patients about newer treatment options Published online 14 September 2017 since patients clearly could not afford them. “These kinds of exorbitant prices should be addressed by the government,” said Menghaney, who is associated with The Union for Af- fordable Cancer Treatment (UACT). While affordable access to medicine has been a thorny issue in In- dia, experts have long underscored that creating such access cannot LET’S GET be done in isolation and needs a combination of events such as ro- bust treatment infrastructure and distribution pathways across India. SOCIAL PATIENT ASSISTANCE PROGRAM MSD, as Merck is known outside of the US and Canada, said that Key- We are tweeting, liking and sharing the latest truda had been launched for the treatment of advanced melanoma industry news and insights from our global in India in line with the firm’s comprehensive approach to fostering team of editors and analysts, join us! patient access for approved indications. “Specifically, for advanced melanoma, we are introducing Keytru- @PharmaScrip da with an India-specific price and Patient Access Program to assist patients who otherwise could not afford treatment,” MSD India told

16 | Scrip | 22 September 2017 © Informa UK Ltd 2017 COMPANY

Alexion Restructuring Deemed A Necessary Evil JOHN DAVIS [email protected]

lexion Pharmaceuticals Inc. drew a line under recent dis- launched in Germany after it gained EU approval in August. “If all appointing events when it announced a series of changes goes well, we’ll be prepared for a launch [of the indication] in the US Aearlier this week that included moving its headquarters from followed by Japan,” he remarked. New Haven, Connecticut to Boston and reducing its workforce by Hantson also noted that first launches of ALXN1210 could occur at 20%, changes that were cautiously welcomed by analysts but caused the beginning of 2019. The product is a long-acting anti-C5 antibody dismay in the locations being left behind. that inhibits terminal complement and is in Phase III clinical studies in Shares in the US company initially declined to $140 from $142 on patients with paroxysmal nocturnal hemoglobinuria and those with Sept. 11, the day the restructuring was announced, but had increased atypical hemolytic uremic syndrome. to $146 per share on Sept. 14 as investors digested the restructuring and corporate strategy. Alexion said the changes held out the promise of making $270m in GAAP pretax savings annually by 2019, and company is expecting to invest around $100m to build up its R&D pipeline through business development moves and the approval of additional complement-related indications for its products. The total pre-tax restructuring expenses are estimated at $340m to $440m. Pharma analysts were generally positive about the announced changes. Deutsche Bank analysts said the changes were consistent with previously announced plans to focus on the pipeline, although the cost savings were broader than expected. Credit Suisse analysts said: “We view today’s update as incremental in providing significantly more details around how they can be best positioned for long- term top and bottom line growth.” However, top-line growth likely will require deals, acquisitions and licensing, they added. AleMasche72 Shutterstock: In contrast, the restructuring plans were greeted with disappoint- Restructuring is a difficult process ment in the locations most affected, including the state of Connecti- cut, where the company’s HQ was seen as a focal point for the area’s R&D DISCONTINUED, SITES CLOSED biotech community. Of course, the restructuring means that some investigational pro- The key issues faced by newly appointed CEO Ludwig Hantson are grams and company collaborations will end. These include the de- ones that have troubled many a company leadership in the past – prioritizing of the potential replacement therapy, ALXN1101, and the reliance of Alexion on one product, in this case the blockbuster samalizumab (ALXN6000) and the ending of partnerships with Mod- Soliris (eculizumab), increasing pressure on prices, and efforts to find erna Therapeutics LLC, Blueprint Medicines Corp. and Arbutus new streams of revenues. Soliris accounted for $2.84bn of Alexion’s Biopharma Corp. $3.08bn in revenues for 2016. Hantson was appointed in March 2017 A number of Alexion sites will be closed, including a manufac- after the ultra-rare disease drug developer was rocked by a sales au- turing facility on Rhode Island in the US and certain regional and dit investigation – which subsequently found inappropriate but not country-based offices, and Alexion will relocate its headquarters by illegal behavior – and after the resignation or retirement of several of the middle of 2018 to Boston, Massachusetts, where it will employ its top executives. (Also see “Alexion CEO Hantson Tasked With Kicking around 400 individuals; a research center of excellence with around Growth Momentum Into Gear” Scrip, 27 Mar, 2017.) 450 positions will remain in New Haven. In a briefing about the restructuring with analysts, Hantson out- The attractions of Boston’s biotech sector are well known by the lined the company’s key objectives as: “Growing our rare disease pharma community, and were outlined by Alexion as providing “ac- business, focusing research on our complement expertise and de- cess to a larger biopharmaceutical talent pool, and a variety of life velopments in our core therapeutics areas, pursuing disciplined busi- science partners to further support future growth initiatives.” ness development to expand the pipeline, and optimizing our in- The company is cutting a swathe through a number of employee frastructure to deliver margin expansion, earnings-per-share growth functions. It aims to outsource certain non-core finance and IT roles, and increased cash flow.” and will trim certain G&A functions including human resources. Core areas including hematology, nephrology, neurology and Among commercial teams, investments are to be aligned with core metabolic disorders, with Hantson explaining that “we’ll open up high growth markets, with what seems to be the consolidation of a little bit from ultra-rare to rare, but we stay in the orphan disease management: synergies will be exploited across regions and coun- space.” tries, Alexion said. However, there also will be a focus on continuity In its late-stage R&D pipeline, Hantson highlighted myasthenia in the company’s field teams. Hantson said field teams in the US, gravis as a new indication for Soliris, and the potential of the next- Germany and Japan will be expanded to serve patients with refrac- generation C5 inhibitor, ALXN1210. Brian Goff, chief commercial of- tory myasthenia gravis. ficer, reported the myasthenia gravis indication for Soliris had been Published online 14 September 2017 scrip.pharmamedtechbi.com 22 September 2017 | Scrip | 17 INTELLECTUAL PROPERTY

Mylan Calls Allergan Restasis Patent Deal A ‘Desperate Tactic’ JESSICA MERRILL [email protected]

Indeed, the payment to the Mohawk tribe panies to act similarly as the industry has does bring to mind the pay-for-delay tactics faced growing criticism on the high cost used by the industry in the past to postpone of drugs. generic launches, and which have been de- However, in an interview with Scrip when clared anti-competitive by the Federal Trade the deal was announced, Saunders main- Commission. tained that the deal is consistent with the Mylan is one of the companies that is social contract as one of the elements was challenging Allergan’s Restasis patents, a commitment to innovation, and Restasis which extend to 2024, both through the was an innovative drug. courts and an inter partes review at the US But paving the way for eventual ge- Patent and Trademark Office. The court trial neric competition is an important ele- was completed on Sept. 8 and the oral argu- ment of what helps to keep the cost ment in the IPR proceedings is set for Sept. of drug spending down, and when it Shutterstock: Yuganov Konstantin Yuganov Shutterstock: 15. The other defendants in the court pro- comes to challenging intellectual prop- ceedings are Teva Pharmaceutical Indus- erty protection, many people agree the ylan NV responded quickly to tries Ltd. and Akorn Inc. process should be left to the US courts Allergan PLC’s controversial deal to decide. Mwith a Native American tribe to Being called out by Allergan, for its part, has responded that shield its blockbuster dry eye therapy Resta- while it accepts the patent proceedings sis (cyclosporine) from generic competition, Mylan for nefarious under Hatch Waxman and in the courts, it calling it a “desperate tactic” to protect the takes issue with the IPR proceedings, which Restasis patents in a court filing on Sept. 11. wheeling and dealing have effectively become double jeopardy. Mylan said it is examining the Allergan only highlights just what IPR proceedings have invalidated several deal and whether or not it is anti-compet- patents, including two recently for Humira itive, as well as how it could impact the a high-risk calculation (adalimumab). (Also see “PTAB Tosses Two pending patent litigation in the Marshall, More Humira Patents; Will Supreme Court Texas, court. Allergan has made with Eliminate IPR Proceeding?” Pink Sheet, 14 Jun, “Allergan’s desperate tactic further dem- 2017.) However, the US Supreme Court has onstrates what was presented in detail at its reputation agreed to hear a case challenging the con- the trial held in this matter, that the patents stitutionality of the proceedings. covering Allergan’s Restasis product are in- Allergan already received a lot of public valid,” the correspondence says. Being called out by Mylan for nefarious backlash following the announcement of Under the controversial deal an- wheeling and dealing only highlights just the deal, and that could grow to encom- nounced by Allergan on Sept. 9, the com- what a high-risk calculation Allergan has pass the industry more broadly if the le- pany agreed to transfer patents for Resta- made with its reputation. Mylan is con- gality of the deal is deemed acceptable sis to the Saint Regis Mohawk Tribe and sidered by some to be the poster child and others try to make similar maneuvers. pay the tribe $13.75m up front and $15m for what not to do to avoid the public’s (Also see “Too Bold By Half: Allergan’s Lat- in annual royalties. Allergan appears to wrath when it comes to social responsi- est Moves And Pharma’s Leadership Deficit” be trying to take advantage of the tribe’s bility. After the outcry that arose over the Scrip, 12 Sep, 2017.) status as a sovereign nation to preempt high price of EpiPen (epinephrine) last Some analysts and legal experts believe efforts to invalidate the Restasis patents year, many in the industry have tried to that could be the case, and from the busi- via the inter partes review (IPR) process by paint Mylan as an outlier in an industry ness vantage, many view the deal as inno- the US Patent and Trademark Office’s Pat- that is largely focused on innovation and vative play to extend the life of a valuable ent Trial and Appeal Board. R&D investment. brand. The drug industry has certainly “That Allergan is attempting to misuse The big irony here is that Allergan CEO never been shy about pulling out all the Native American sovereignty to shield in- Brent Saunders has stepped outside the stops to protect its biggest revenue gen- valid patents from cancellation is further box on the issue of drug pricing and social erators in the past – and the pressure re- evidenced by the fact that Allergan paid the responsibility. He was the first CEO to an- mains as intensive as ever to continue to Saint Regis Mohawk tribe to take the assign- nounce a social contract on drug pricing do the same. ments,” Mylan points out in its court filing. and has advocated for other drug com- Published online 13 September 217

Bayer’s Aliqopa Approval Gives PI3K Class A Second Chance in Follicular Lymphoma EMILY HAYES [email protected]

he class of PI3 kinase inhibitors will get a second shot at pen- by 2021. Roche’s anti-CD20 therapy Gazyva (obinutuzumab) is being etrating the market for follicular lymphoma, following accel- positioned as a successor to Rituxan. T erated approval of Bayer AG’s Aliqopa (copanlisib) for use as “We think Roche’s Rituxan and next-generation CD20 antibody Ga- a monotherapy after two prior systemic therapies, but the drug will zyva remain well-positioned as treatment backbones in these markets,” need to prove it is safe and efficacious in combination regimens in the Morningstar report said. Phase III to come into wider use. New classes are being positioned as monotherapies in later lines of The drug cleared the US FDA on Sept. 14, and Bayer is planning to therapy and as part of combination regimens in earlier lines. Gilead launch the drug immediately at the monthly wholesale acquisition Sciences Inc.’s oral PI3 kinase inhibitor Zydelig (idelalisib) was ap- cost of $12,600. The company notes that patients may get assistance proved for later-line treatment of FL in July 2014, having demonstrated with reimbursement access and expenses through its new Aliqopa Re- a 54% ORR as a single agent in a single-arm study. But safety problems source Connections program. combining with other therapies have limited its potential to move to earlier lines of treatment. (Also see “Zydelig Takes Major Hit, But Not A Big Blow For Gilead” Scrip, 14 Mar, 2016.) ‘We think Roche’s Rituxan and Despite its first-mover advantage in the market, Morningstar ana- Gazyva remain well-positioned lysts note that its use has been limited to “only the most advanced patients,” because of adverse events. Zydelig, which also is approved for as treatment backbones in these chronic lymphocytic leukemia, has a boxed warning for fatal and/or severe hepatotoxicity, diarrhea and colitis, pneumonitis, infections and markets’ intestinal perforation. Aliqopa has no boxed warning. Labeling advises that the most common adverse reactions, occurring in more than 20% of patients, are hy- According to the National Cancer Institute and National Institutes of perglycemia, diarrhea, decreased strength and energy, hypertension, Health, 72,740 people will be diagnosed with non-Hodgkin lymphoma leukopenia and neutropenia, and lower respiratory infections. this year in the US; the drug holds orphan status. Follicular lymphoma “While there were some side effects, like hyperglycemia, hyperten- is a slow-growing (indolent) subtype that accounts for about 35% of sion and liver enzyme elevations, there appeared to be lower rates of NHL cases overall. the gastrointestinal and infection-related side effects that weighed on Copanlisib is one of six mid- to late-stage pipeline drugs that Bayer Zydelig’s broader potential,” Morningstar analysts noted. has been counting on to bring in peak annual sales of at least €6bn The Phase III studies could enable copanlisib to expand into use in ($7.2bn), in total. (Also see “Bayer Bets On Oncology Pipeline, Vows To combination regimens, but “other side effects, like hyperglycemia and Increase 2017 R&D Budget” Scrip, 22 Feb, 2017.) hypertension, could limit first-line use,” the Morningstar report said. Bayer’s filing was supported by a single-arm Phase II study of Datamonitor Healthcare analysts noted in a March 2016 report that 104 patients with follicular B-cell NHL who relapsed after two prior the lack of Phase III data for copanlisib makes it difficult to compare treatments. The drug demonstrated an objective response rate to Zydelig in third-line treatment. In the second-line setting, the drug (ORR) of 59%. may face no competition from Zydelig. However, copanlisib also has a Bayer has two Phase III studies ongoing. The CHRONOS 2 disadvantage of being given intravenously, whereas Zydelig and other study tests Aliqopa against placebo in patients with indolent PI3 kinase inhibitors, as well as drugs from other classes like BTK inhibi- NHL (iNHL) refractory to Roche’s anti-CD20 Rituxan (rituximab) tors, are given orally. and is due to complete in May 2018. The CHRONOS 3 study tests Verastem Inc.’s oral PI3 kinase inhibitor duvelisib, licensed from In- Aliqopa in combination with Rituxan in iNHL patients who have finity Pharmaceuticals Inc., also is being positioned for a role in FL relapsed after one prior therapy, including Rituxan; this trial is and is in late-stage development for this indication, but the drug does set to wrap up in March 2020. not look very competitive based on response rates in the Phase II Dy- Copanlisib also is in Phase II for diffuse large B-cell lymphoma namo study. In that trial, the ORR was 41% in follicular lymphoma pa- and Phase I for solid tumors. tients and there were no complete responses. (Also see “Infinity Doesn’t Sugarcoat Disappointing Duvelisib Data” Scrip, 20 Jun, 2016.) TEAMING UP WITH RITUXAN TG Therapeutics Inc.’s oral PI3 kinase inhibitor umbralisib (TGR- Treatment for FL is dominated by Rituxan, which is used with che- 1202) is in Phase II/III. motherapy combinations for first-line and maintenance treatment. “Beyond copanlisib, studies are too early to determine whether an- Morningstar analysts noted in a July 2017 market report about other PI3K could move to the first-line setting or improve safety,” the blood cancers that Rixuan had $4.5bn in sales for NHL and that the Morningstar report concluded. total market was worth $5.7bn, which is projected to rise to $11.8bn Published online 14 September 2017 scrip.pharmamedtechbi.com 22 September 2017 | Scrip | 19 BUSINESS STRATEGY

Novo Nordisk Prepares Victoza’s China Launch STEN STOVALL [email protected]

he inclusion of Victoza (liraglutide) on China’s National Reim- regions to ensure it gets used there locally while continuing bursement Drug List (NRDL) represents a huge commercial to have a dialogue with the federal government, so that when T and medical opportunity for Novo Nordisk AS, which now the time came for opening the national drug Victoza had what plans a nationwide roll-out the GLP-1 in the world’s second-largest was needed to register and be considered for use nationally,” drug market next January, the Danish group’s international opera- he explained. tions head told Scrip. Novo Nordisk is hoping for a similar evolution for its fast-acting China’s Ministry of Human Resources and Social Security earlier basal insulin Tresiba (insulin degludec). this year added 39 drugs to the NRDL in return for steep price cuts. It “We expect approval of Tresiba in China by the end of this year, was the first time in eight years that the list had been opened to new and a launch immediately after that – which will at least six months therapies for routine reimbursement throughout the country. earlier than we had been previously expecting, and that happened Victoza consequently became the first GLP-1 to be listed on the Chi- because Tresiba’s evaluation was accelerated by the Chinese authori- nese NRDL, and reimbursement is expected to be obtained across Chi- ties,” Doustdar said. na as the provincial drug reimbursement lists are updated accordingly. Tresiba is already available in some 60 other countries. The fact it’s “So Victoza will get full access there, and we have high hopes for its not on China’s NRDL means it will have a slow roll-out there. “We can- roll-out and thereby increase our GLP-1 share of the Chinese market not expect a quick uptake of Tresiba in China until access is arranged with that drug,” Novo Nordisk’s Maziar Mike Doustdar said to Scrip province by province, and that will take time.” on the sidelines of this year’s European Association for the Study of Doustdar said the long periods during which admission is de- Diabetes (EASD) congress in Lisbon, Portugal. nied to new drugs is in large part due to cost considerations. “If they opened it up on an annual basis, then than would potentially pave GLP-1 ADVANTAGE the way for innovative drugs for more than a billion people, and that Doustdar said getting on the NRDL means Victoza gets ‘first-mover’ has cost implications.” advantage in the GLP-1 space there. “GLP-1 is about 11% of the entire global diabetes market’s value. In MOUSE THAT ROARED the US, it’s around 12%, in Europe it’s around 7%, in emerging mar- A Danish trade delegation which recently visited authorities in China kets it’s around 4%, but in China it’s around 1% ... No matter what included the Danish Prime Minister. There is currently a collaboration market you use as reference, there’s clearly a lot of room for growth between Novo Nordisk, the Danish Medicines Agency, and the Chi- implied for us in China with this drug type,” he said. nese Food and Drug Administration on how to build world class into An extra advantage is that Eli Lilly & Co.’s a once-weekly GLP-1 all elements of their drug approvals. inhibitor Trulicity (dulaglutide) is not on China’s NRDL. “I am extremely excited about the collaboration between the Dan- “Trulicity, which is perhaps our biggest competitor in the segment, ish Medicines Agency and the SFDA [China’s State Food and Drug is not available there yet so we have … a good upside on our side to Administration], said Doustdar, who was part of that visiting delega- really make the most of that, and we are now working out those plans tion last November and which included with Denmark’s prime min- which will in many ways represent a re-launch of Victoza in China.” ister Lars Løkke Rasmussen, together with the head of the Danish “We have had the product in there but in a very fractured, piece- Medicines Agency. meal fashion. You will start to see a different type of uptake of Victoza Doustdar, who is of Iranian origin, said that “during the visit the there hopefully at the start of next year. We are currently negotiating head of the SFDA applauded Novo Nordisk’s activities in China, be- with those 31 provinces. I assume that at the end of December those cause we not only have a very large production site there, but we negotiations will have concluded, and that by Jan. 1 then we could have a very large research center there and we are by far the largest more or less move to making it more or less available everywhere in Danish company in China.” China,” Doustdar said. He said Denmark’s cradle-to-grave welfare state and healthcare Doustdar said Victoza’s inclusion on the NRDL was the product of system has attractions to Chinese authorities. a step-by-step approach. “I think the Chinese look with approval at the Danish system bal- “You need to register a drug in China to be able to market it but if it ancing both access in somewhat a socialistic way regarding medi- is not on national reimbursement then you need to go to each of the cines for their population, while healthcare is mandatory and it’s 31 provinces in China individually and negotiate your way through good and works, while not fully bankrupting their system, like some the reimbursement process, and the uptake is pretty slow. But that other European healthcare systems have virtually done by not mak- changes when you’re put on the so-called national drug list whereby ing ends meet.” the government induces the provinces to take on the drug, allow- He said the Danish companies best known in China are Lego, ing for a much quicker pace of pick-up by the provinces, occurring Carlsberg and Novo Nordisk. within three to six months, at which point the drug becomes free of “Novo Nordisk is a niche business - so to have a brand similar in rec- charge for patients there,” he explained. ognition to Lego and Carlsberg which are more consumer-oriented “Victoza was first approved by Chinese regulators around products and companies, was probably a compliment.” three years ago, and since then we have been working with the Published online 14 September 2017

Pfizer Poised To PROSPER From Xtandi JESSICA MERRILL [email protected]

ositive Phase III data on the prostate cancer drug Xtandi (enzalutamide) Pin an expanded indication will take some of the edge off at Pfizer Inc., where the brand’s near-term growth prospects fizzled right after the expensive acquisition of Medivation Inc. Pfizer and Xtandi marketing partner Astellas Pharma Inc. announced positive top-line data from PROSPER on Sept. 14. The results showed that non-metastatic, castration-resistant prostate cancer (CRPC) patients treated with Xtandi and androgen deprivation therapy (ADT) had improved metastasis-free survival versus patients treated with ADT alone.

Expansion into the earlier prostate can- Nichiata Carla Shutterstock: cer setting would greatly expand the commercial market for Xtandi – a significant A POTENTIAL BUMP AFTER A get population. This eases investor concerns driver behind Pfizer’s $14bn acquisition DIP IN SALES around consensus estimates, which had of Medivation last year. (Also see “Pfizer’s After closing of the expensive Mediva- Xtandi going from less than $600m run rate $14bn Medivation Buyout Shows How Far tion acquisition last year, sales of Xtandi in US now to $1bn+ in 2020 amidst this Pharma Will Go In Oncology” Scrip, 22 Aug, hit a roadblock in the US, not because of evolving [prescription] trajectory in the ex- 2016.) Pfizer previously said expansion demand, but due to what Pfizer manage- isting indication.” into the non-metastatic population would ment viewed as short-term anomaly, an in- double the commercial opportunity for creased use of patient assistance programs PROSPER RESULTS AMENDED Xtandi. There are about 30,000 to 35,000 to pay for treatment. US sales of Xtandi FOR FASTER ANALYSIS patients in the US with non-metastatic declined 11% in the first quarter, resulting Pfizer and Astellas successfully sped up the CRPC, the company said during a presen- in some backlash from investors over the data results by nearly two years by amend- tation at the American Society of Clinical valuation of the deal. Second quarter sales ing the PROSPER trial earlier this year. The Oncology (ASCO) meeting last year. were also below analyst expectations as trial was originally expected to read out in Pfizer and Astellas said they plan to dis- the challenge continued. Although Xtandi June 2019. The main change was to review cuss the results with global health authori- is a blockbuster, Pfizer shares sales and prof- the analysis plan for the primary and sec- ties to support an expanded indication for its in the US with Astellas, which also mar- ondary endpoints, paving the way for a re- the androgen receptor inhibitor, which is kets the drug outside the US and pays a duction in the target sample size to around already approved for men with metastatic royalty on sales to Pfizer. 1,440 from 1,560. The companies said the CRPC. It was developed by Medivation and Expansion into a broader patient setting change would accelerate the collection and approved in 2012 for the treatment of ad- should go a long way to alleviate investor evaluation of the data. vanced metastatic prostate cancer after concerns at Pfizer, especially since rival Zyt- The Phase III trial enrolled 1,400 patients chemotherapy based on improvements in iga is expected to face generic competition with non-metastatic CRPC that had pro- overall survival; the label was expanded in in the second half of 2018, which could also gressed, based on a rising prostate-specific 2014 to include pre-chemo patients. impact sales of Xtandi. antigen (PSA) level despite ADT, but who While Xtandi competes with Johnson & “These results are one of several key had no symptoms with no prior or present Johnson’s Zytiga (abiraterone) in the meta- catalysts for Pfizer in the near term,” BMO evidence of metastatic disease. The primary static setting, there are no FDA-approved Capital Markets analyst Alex Arfaei said in a objective of the trial was metastasis-free sur- treatments for patients with non-metastatic same-day research note. “We forecast peak vival, measured as the amount of time that CRPC until they develop confirmed radio- Xtandi revenue (Pfizer’s share) at $2.7bn passes until a cancer can be radiographical- graphic metastatic disease. In the case of by 2027 with 30% coming from the [non- ly detected as having metastasized to other PROSPER, the trial was evaluating patients metastatic] setting.” parts of the body. whose cancer had progressed based on ris- Evercore ISI analyst Umer Raffat noted Pfizer expects to release the full data at a ing prostate-specific antigen (PSA) levels, in an email to investors, “PROSPER trial just future medical meeting. but with no metastatic disease. added a brand new leg of growth and tar- Published online 14 September 2017

scrip.pharmamedtechbi.com 22 September 2017 | Scrip | 21 PIPELINE WATCH

Scrip’s weekly Pipeline Watch tabulates the most recently reported CLICK late-stage clinical trial and regulatory developments from the more Visit scrip.pharmamedtechbi.com than 10,000 drug candidates currently under active research worldwide. for the entire pipeline with added commentary.

Selected clinical trial developments for the week 8–14 September 2017

LEAD COMPANY/PARTNER COMPOUND INDICATION COMMENTS Phase III Suspended Prostvac (rilimogene Bavarian Nordic AS prostate cancer PROSPECT; deemed futile on interim analysis . galvacirepvec) Amicus Therapeutics Inc. SD-101 epidermolysis bullosa ESSENCE; missed primary endpoint. super-refractory status SAGE Therapeutics Inc. brexanolone STATUS; missed primary endpoint. epilepticus Livatag (doxorubicin) Onxeo SA liver cancer ReLive; missed primary endpoint. Transdrug Phase III Results Published AstraZeneca PLC Farxiga (dapagliflozin) diabetes, type 1 DEPICT-1; The Lancet, Sept. 14, 2017. Eli Lilly & Co. Cyramza (ramucirumab) bladder cancer RANGE; The Lancet online, Sept. 12, 2017. melanoma, BRAF V600E/K Mekinist (trametinib) Novartis AG mutation positive, early COMBI-AD; NEJM, Sept. 8, 2017. plus Tafinlar (dabrafenib) stage AstraZeneca PLC Bydureon (exenatide) diabetes, type 2 EXSCEL; NEJM online, Sept. 14, 2017. Sanofi/Lexicon Pharmaceuticals Inc sotagliflozin diabetes, type 1 inTandem3; NEJMonline, Sept. 13, 2017. GlaxoSmithKline PLC mepolizumab eosinophilic COPD METREX, METREO; NEJM online, Sept. 12, 2017.C Clovis Oncology Inc. Rubraca (rucaparib) ovarian cancer ARIEL3; The Lancet online Sept. 12, 2017. Amgen Inc. Evenity (romosozumab) osteoporosis ARCH; NEJM online, Sept. 11, 2017. Breo/Relvar (fluticasone/ GlaxoSmithKline PLC/Innoviva Inc. asthma The Lancet online, Sept. 10, 2017. vilanterol) Bristol-Myers Squibb Opdivo (nivolumab) melanoma CheckMate-238; NEJM online, Sept. 10, 2017. Updated Phase III Results Eli Lilly & Co. lasmiditan (oral) migraine SPARTAN; reduced pain. chronic and episodic Teva Pharmaceutical Industries Ltd. fremanezumab HALO; reduced headache, well tolerated. migraine prevention AstraZeneca PLC Imfinzi (durvalumab) NSCLC PACIFIC; improved PFS. CheckMate-017, 057; survival benefit at Bristol-Myers Squibb Co. Opdivo NSCLC three years. Eli Lilly & Co. abemaciclib breast cancer MONARCH3; positive results . Medigen Biotechnology Corp. muparfostat liver cancer PATRON; mixed results. Argos Therapeutics Inc. rocapuldencel-T renal cell carcinoma ADAPT; mixed results, study continuing. adalimumab, biosimilar Novartis AG psoriasis ADACCESS; positive data. to Humira glycopyrronium tosylate, Dermira Inc. axiliary hyperhidrosis ATMOS-1, -2; improved symptoms. topical cisplatin-induced hearing Fennec Pharmaceuticals Inc. sodium thiosulfate SIOPEL6; encouraging signs. loss Novartis AG Cosentyx (secukinumab) psoriasis Sustained benefit over five years. Source: Biomedtracker View full results here: http://bit.ly/2hjcxAW

Santhera Shares Sink On Duchenne Setback in Europe KEVIN GROGAN [email protected]

he week could not have ended worse so well for Santhera after it announced 2014 and is now available to eligible pa- for Santhera Pharmaceuticals AG that Raxone is now being used to treat tients in the UK. T as its share price sank after European DMD patients under the UK’s early access Observers will be looking to see where regulators recommended against approval of to medicines scheme (EAMS). That will re- Santhera can go from here, given that its investigational Duchenne muscular dystro- main valid until a final regulatory decision the US FDA has also been less than im- phy hope Raxone (idebenone). has been reached by the European Union. pressed with Raxone for DMD. Last year, The Swiss group’s stock closed down Patient groups, which are particularly vo- the agency asked Santhera for further almost 46% on Sept.15 to 38.75 francs, cal in the DMD field, were also unhappy. Still, data before it considers the therapy for which was some improvement on an Muscular Dystrophy UK said that while it is approval. (Also see “Santhera Setback earlier plunge of nearly 60%. The market disappointed by the news, “we would like to Could Have Wide-Reaching Effects For DMD response was unsurprising given that the reassure UK patients that families enrolled or Drugs” Scrip, 14 Jul, 2016.) Committee for Medicinal Products for Hu- planning to enrol in the EAMS should not be Raxone is already approved for Leber’s he- man Use (CHMP) of the European Medi- affected. We welcome the news that San- reditary optic neuropathy and contributed cines Agency adopted a negative opinion thera are planning to appeal the decision.” 10.9 million francs to Santhera’s coffers in the for Santhera’s application to expand ap- The group’s director of campaigns, care first half of 2017, up 51% on the like, year-earli- proval of Raxone to include DMD. and information Nic Bungay noted that er period. Last week, the company noted that Santhera said it plans to appeal the opin- the negative opinion is indeed disap- in the last few months, its commercial op- ion and will seek a re-examination by the pointing “but not unprecedented in the erations in Europe were increased to support CHMP. Chief executive Thomas Meier said regulation process.” He cited the case of marketing of the drug for LHON “and to pre- he was “surprised and disappointed “ at the another DMD drug, PTC Therapeutics pare for a timely market entry of Raxone for decision and the company expects to find Inc.’s Translarna (ataluren), which was DMD,” the company added. After the CHMP’s out if its appeal has been successful in the initially rejected by the CHMP but finally decision, the wait could be a long one. first quarter of 2018. The week had started got conditional approval from the EMA in Published online 18 September 2017

APPOINTMENTS

Gyroscope Therapeutics, an ophthalmol- ence, gained from companies such as Bayer general manager pharmaceuticals at Harlan ogy company focused on retinal diseases, HealthCare LLC, GlaxoSmithKline PLC and Laboratories and vice president corporate has appointed Soraya Bekkali CEO, chief Novartis AG. and medical affairs at DeveloGen AG. medical officer and director of its board. Be- fore Gyroscope, Bekkali was senior vice presi- Horizon Pharma PLC. has named Irina Timothy A. Marcotte has joined Adheri- dent and chief medical officer of Lysogene Konstantinovsky executive vice presi- um Ltd. as chief financial officer and will be SAS and previously, she was global head of dent, chief human resources officer – ef- based in the company’s US headquarters in the ophthalmology business unit at Sanofi, fective immediately. Before this, Konstanti- San Mateo, California. Marcotte brings over where she spent 10 years in various positions. novsky was vice president of global talent 35 years’ experience to Adherium and pre- at Baxter International Inc. viously worked at various medical device Keith A. Katkin has been elected Urovant companies, including Zonare Medical Sys- Sciences’ CEO and most recently, he was Veloxis Pharmaceuticals Inc. has ap- tems Inc., VNUS Medical Technologies Inc., president and CEO of Avanir Pharmaceu- pointed Ulf Meier-Kriesche, a nephrolo- and Repeater Technologies. ticals Inc. Katkin joined Avanir in 2005 as gist with over 20 years of clinical experience, senior vice president of sales and market- chief scientific officer. Prior to this position, TiGenix NV has appointed Gregory Gor- ing and before this, he was vice president, Meier-Kriesche was the clinical trials lead don head of medical department. He joins commercial development for Peninsula immunology at Bristol-Myers Squibb Co. the company from Nestle Health Science Pharmaceuticals Inc. SA, where he was global clinical affairs lead, Thomas Knittel has been appointed Mo- gastrointestinal health. Previously, Gordon Nevoii Pharmaceuticals AG’s CEO, Alex- dus Therapeutics’ chief medical officer held roles at Stealth BioTherapeutics Inc., andre Sudarskis, is to retire and will be re- (CMO) and joins the company from Prima Ironwood Pharmaceuticals Inc., and Pa- placed by Juergen Pohle – effective Jan. 1, Biomed, where he was executive vice presi- ralex Inc. In addition to this, Annette Valles- 2018. Pohle has been chief commercial of- dent medical & scientific development. He Sukkar has been named associate director, ficer of the company since March 2016 and has been acting CMO for InDex Pharmaceu- clinical project. Valles-Sukkar joins TiGenix in addition to his role as CEO, he has also ticals AB since 2012. Knittel has also previ- from Alexion Pharmaceuticals Inc., where been appointed managing director of the ously held positions as business unit direc- she was responsible for all aspects of clini- company. He has 25 years’ worth of experi- tor at Novo Nordisk AS for central Europe, cal trial development. scrip.pharmamedtechbi.com 22 September 2017 | Scrip | 23 scrip_press_ad_297x210_v5_HR.pdf 1 2017/09/18 1:03 PM

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