26 April 2019 No. 3952

Scripscrip.pharmaintelligence.informa.com Pharma intelligence | informa

“Gene therapies have the potential to actually cure disease, and consequently the value of that to the healthcare system can be huge, not only for the patients who suffer from that disease but also from a cost perspective because you save a lot of follow-on costs and I would add, go beyond that from a societal perspective, if those patients are really cured, as they can go back to work and make their contribu- tions paying taxes, social contributions, etc.,” Schwan said. “Having said that, what is special with gene therapies is that you get this up-front treatment and that can in- deed be a one-off burden for a health- care system and I believe we will need to find innovative approaches and new pricing models.” The issue will become more relevant once Roche takes control of Philadelphia- Roche CEO: Novel Gene Therapies based Spark Therapeutics, which it has offered to buy for $4.8bn and which, after Justify New Payment Models a regulatory delay, is expected to close in the first-half of the year. STEN STOVALL [email protected] Roche views Spark as a valuable prize, largely due to its gene therapy for he up-front, one-off payment mod- systems and society as a whole. He also a rare type of blindness which the US el for patients being treated with said the advent of gene therapy, which FDA approved in 2017, known as Lux- Trevolutionary gene therapies isn’t introduces new genetic material into a turna (voretigene neparvovec). tenable given the huge burden their high person’s DNA, also promises to reduce The Swiss major’s proposed acquisi- prices would place on healthcare systems, the burden of disease on society in gen- tion of Spark Therapeutics gives it a but any solution must adequately com- eral by providing cures, and that a bal- leading seat at the table in the emerg- pensate the biopharmaceutical groups ance therefore needs to be found that ing field of gene therapy, and thus fu- that develop and commercialize them, might involve spreading the cost of the ture conversations with patient groups, says the CEO of Roche. medicines out over time. payers and HTAs. Speaking to journalists during the “I could well imagine that, rather than Swiss group’s first-quarter update – in GENE THERAPY NEEDS NEW having one-off payment at the beginning which he said Roche’s delayed takeover COMMERCIAL MODEL of the treatment, to actually spread out of US-based gene therapy company “The values of gene therapies can be tre- the payment over several years and link it Spark Therapeutics Inc. remained “on mendous for the system, but we need to to the performance of the medicines,” he track” – Severin Schwan acknowledged find new, innovative approaches to make told reporters. “That approach offers risk that expensive gene therapies could put it sustainable for our partners in the sys- sharing between the providers of such unmanageable stresses on healthcare tem,” the Austrian CEO said. CONTINUED ON PAGE 4

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

Bit By Bit Sky High R&D Updated NASH Notebook Small biotechs at risk if NAS launches reach Developments and diagnoses piecemeal pricing takes hold (p4) record levels in 2018 (p7) from EASL 2019 (p18-20) IN THIS ISSUE

from the executive editor [email protected]

As the first-quarter results reporting season kicks off, pharma or stop developing these products altogether. the tricky issue of pricing models for expensive one- See pages 1 and 4 for more details. time treatments is again to the fore. In light of its In R&D news, the European Association for the Study upcoming purchase of gene therapy pioneer Spark of Liver Disease meeting in Vienna, Austria, saw research Therapeutics, Roche CEO Severin Schwan has joined on efforts to diagnose non-alcoholic steatohepatitis and other companies developing gene therapies, like Swiss its precursor non-alcoholic fatty liver disease better. The rival Novartis, in highlighting the need to develop issue has became more urgent after the US Food and Drug novel systems to spread their cost if long-term benefit Administration issued draft guidance recommending that can be proven. But where would such systems leave drug sponsors work on such diagnostic tools because smaller companies which are less able to absorb the fi- of the burden and expense of liver biopsies, the current nancial impact of annuity payments? Some experts say standard, and will help when the new wave of therapies for biotechs – which in theory should be able to market this disease come to market. Read more on p18. such specialist products themselves without the need Finally, the industry can congratulate itself on its best for large marketing muscle – could be so fearful of the year of the century in terms of new active substance potential impact that they off-load their assets to big launches in 2018. All the details are on p7.

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

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

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

Scrip is published by Informa UK Limited. ©Informa UK Ltd 2019: All rights reserved. ISSN 0143 7690.

2 | Scrip | 26 April 2019 © Informa UK Ltd 2019 Boehringer’s Roche’s Asian Impact Janssen’s MD Exits Diabetes Success

20 11 14 21

exclusive online content inside: COVER / Roche CEO: Novel Gene Therapies Justify M&A A Major Pillar Of Sumitomo New Payment Models Dainippon’s New Mid-Term Plan 4 Annuity-Based Pricing Models Could Mean Problems IAN HAYDOCK [email protected] For Small Biotechs

6 Lilly/Pfizer’s Tanezumab Safety Takes A Hit With Latest Phase III Results

7 Purple Patch For Pharma/Biotech R&D As NAS Launches Reach Record High

10 Cassiopea Hails Breezula’s ‘Good Hair Day’ And Plans FDA Talks On Phase III

11 BI Bets On Expanding Jardiance As Diabetes Drug Sales Soar Sumitomo Dainippon Pharma Co. Ltd. is to set aside a total campaign chest of between JPY300-600bn ($2.68- 12 J&J’s Spravato’s Star Power Rises While Zytiga’s Sets 5.36bn) over the next five years to pursue merger and ac- quisition opportunities, with the immediate focus to be on 13 Novartis Secures FDA Priority Review For psychiatry and neurology to fill a mid-term pipeline gap. Thanks To PRV Strategically, the company is looking to ensure sustained growth and develop into what it describes as a “global spe- 14 Asia Begins To See Impact From Roche ‘De-Siloing’ cialized player” by 2033, amid the looming genericization of its top product within this period. 15 Amgen Launches Evenity For High-Risk Osteoporosis As part of a newly unveiled five-year plan covering the At $21,900 List Price fiscal 2018-2022 period, the mid-sized Japanese firm said it would also pursue external partnerships and in-licens- 18 NASH News & Notes From The European Liver Meeting ing across its core areas of therapeutic focus – psychiatry and neurology, oncology and cell therapies/regenerative 19 Thinks KHK Mechanism Could Work For NASH, Diabetes medicines. More broadly, the Osaka-based company said it is targeting group revenues of JPY600bn by the end of 20 Gilead Increasingly Focused On Combo Therapy In NASH fiscal 2022 (in April 2023), versus a forecast for net sales this fiscal year of JPY467bn; half of the target revenue is 21 Janssen India MD To Depart seen coming from the core psychiatry and neurology area. The new plan has been drawn up against the back- 22 Pipeline Watch ground of a need to better adapt to changing global eco- nomic and pharma industry pressures, and ahead of what 23 Appointments SDP expects will be “a significant decline” in both revenue and profit in fiscal 2023, following the loss of US exclusiv- ity in February 2023 for the firm’s global top seller Latuda (lurasidone), an atypical antipsychotic. Published online 15 April 2019 @PharmaScrip /scripintelligence To read the rest of this story go to: https://bit.ly/2KWUqPN

/scripintelligence /scripintelligence

scrip.pharmaintelligence.informa.com 26 April 2019 | Scrip | 3 HEADLINE NEWS/PRICING let’s open our eyes CONTINUED FROM PAGE 1 therapies and payers and, importantly, Annuity-Based Pricing Models Could you avoid these payment peaks, mak- ing it much more sustainable from a fi- Mean Problems For Small Biotechs nancing point of view.” FRANCESCA BRUCE [email protected] “The values of gene ompanies and payers are increas- therapies can be ingly exploring the idea of paying tremendous for the system, Cfor expensive, game-changing pharmaceuticals in instalments over but we need to find new, time rather than in one big initial lump sum. However, such models could lead innovative approaches to small biotech companies to sell their make it sustainable for our assets to big pharma or stop them in- vesting in certain high-risk ventures partners in the system.” - altogether, warned Walter Colasante, a Severin Schwan vice president of life sciences strategy at Charles Rivers Associates. The solution could be to secure a loan The number of potentially one-off treat- using the annuity payments as collateral. ments, like gene and cell therapies, is set However, this could be costly, particularly if to increase. For example, according to the annuity payments are tied to outcomes M&A STRATEGY Charles Rivers Associates, there are some as this increases risk, which will make the THÉA OPEN INNOVATION TAKES ITS FIRST STEPS The logic behind Roche’s targeting of 34 gene therapies currently in pivotal tri- loan more expensive. This could in turn im- Spark Therapeutics was consistent with als. Meanwhile, these therapies, often pact the valuation of the biotech. the company’s M&A strategy, and could touted as curative, are likely to be very ex- Small companies could be forced to Théa Open Innovation has just signed a licence and collaboration agreement for the OLX301A programme, an be seen again in future transactions, pensive, exceeding €1m. Unsurprisingly, pass on the cost of credit to payers, which innovative new treatment for wet and dry age-related macular degeneration, with OliX Pharmaceuticals, a clinical stage Schwan said. payers are concerned about forking out could lead to a higher price for the ther- pharmaceutical company which develops treatments for retinal vascular diseases in particular. Théa Open Innovation is “We expect to close this transaction in such large sums. Not only are they worried apy. Or companies may instead choose the new Laboratoires Théa entity which aims to identify, evaluate and develop new innovative solutions designed by both the first half of this year ... it’s fully in line about budget impact and the sustainabili- to reduce return on investment, which universities and certain research teams and likely to contribute to the development of new treatments for eye diseases. with what our M&A strategy is and has ty of healthcare systems, they are also con- would make the company less appealing Through licensing agreements and / or shareholdings, this new entity plans to offer: been in the past.” cerned about uncertainties over whether to investors, said Colasante. “We have had a number of very early the treatment will work as promised. - its expertise in ophthalmology development and the funding these partners require to conduct proof of concept in stage transactions, in-licensing op- One idea being explored is that payers FINANCIALLY VIABLE? humans portunities, small acquisitions, and oc- make a series of fixed payments over a Such payment models could make it dif- - its ability to manage the regulatory phases of product development and marketing. casionally there are acquisitions of this given time period to spread costs. Those ficult for small biotechs to remain “finan- size where we complement our portfo- payments can also be tied to patient cially viable,” said Colasante. “Only a few Thanks to Théa Open Innovation, small and medium-sized companies, young innovative companies, researchers and lio with respective technologies such as outcomes over the lifetime of a patient. companies with a lot of financing and universities will from now on be able to join forces with Théa Open Innovation to offer tomorrow’s solutions to patients in this case [with Spark]. So yes, it is very Such payment models are being pro- clever people to organize that will be able and health practitioners. much a reflection of our M&A strategy posed “as a last resort” by companies to do that.” which you should expect in future as when other, more traditional approach- Traditionally, commercializing preci- Managed by Henri and Jean-Frédéric Chibret, Laboratoires Théa is a major player in ophthalmology, with a presence in 70 well,” the CEO said. es have failed, for example agreeing sion medicines like gene therapies does countries around the world, more than 25 subsidiaries and a turnover of over €500 million. a confidential discount on a list price, not require the “big muscles of big phar- STRONG FIRST QUARTER Colasante told Scrip. ma companies,” said Colasante. For ex- OliX Pharmaceuticals, Inc. is a Korean clinical stage pharmaceutical company with cp-asiRNA platform technology, an Schwan made the comments when pre- Although such models may help payers ample, because big sales forces are not RNAi platform optimal for the development of ocular therapeutics, which can circumvent potential side effects arising senting the group’s first-quarter sales address affordability and resolve some un- required, small companies can market from the existing siRNA technology. update which, as widely expected, certainties, they could cause sizable prob- the products themselves. But companies saw strong sales growth from newly lems for small biotechs, particularly those may rethink how viable it is to take such launched products off-set the effects with just one asset, warned Colasante. Busi- products to market and “become fearful of biosimilar competition to its cancer ness becomes not impossible, but “more of commercialization.” franchise in Europe, with Ocrevus (ocrel- complicated and more risky,” he said. They may therefore sell assets to big izumab), hemophilia product Hemlibra Receiving smaller lump sums, of, for pharma companies that are able to ab- (emicizumab), Perjeta () and example, €100,000 rather than one big sorb the financial risks and costs. Some let’s open our eyes Tecentriq (atezolizumab) all substantial- payment of €1m could lead to cash flow companies may instead choose to avoid Colin Francou ly surpassing forecasts. problems, said Colasante. As a result, com- developing high risk, complex products [email protected] panies may struggle to pay employees, altogether. Théa Open Innovation Published online 17 April 2019 service debts or cover R&D costs. Published online 16 April 2019 12, rue Louis Blériot • 63017 Clermont-Ferrand Cedex 2 • France

4 | Scrip | 26 April 2019 © Informa UK Ltd 2019

COMMUNIQUE THEA OPEN INNOVATION AVRIL 2019 ang vok.indd 1 18/04/2019 14:34:39 HEADLINE NEWSlet’s open our eyes

THÉA OPEN INNOVATION TAKES ITS FIRST STEPS

Théa Open Innovation has just signed a licence and collaboration agreement for the OLX301A programme, an innovative new treatment for wet and dry age-related macular degeneration, with OliX Pharmaceuticals, a clinical stage pharmaceutical company which develops treatments for retinal vascular diseases in particular. Théa Open Innovation is the new Laboratoires Théa entity which aims to identify, evaluate and develop new innovative solutions designed by both universities and certain research teams and likely to contribute to the development of new treatments for eye diseases. Through licensing agreements and / or shareholdings, this new entity plans to offer: - its expertise in ophthalmology development and the funding these partners require to conduct proof of concept in humans - its ability to manage the regulatory phases of product development and marketing.

Thanks to Théa Open Innovation, small and medium-sized companies, young innovative companies, researchers and universities will from now on be able to join forces with Théa Open Innovation to offer tomorrow’s solutions to patients and health practitioners. Managed by Henri and Jean-Frédéric Chibret, Laboratoires Théa is a major player in ophthalmology, with a presence in 70 countries around the world, more than 25 subsidiaries and a turnover of over €500 million. OliX Pharmaceuticals, Inc. is a Korean clinical stage pharmaceutical company with cp-asiRNA platform technology, an RNAi platform optimal for the development of ocular therapeutics, which can circumvent potential side effects arising from the existing siRNA technology.

let’s open our eyes

Colin Francou [email protected] Théa Open Innovation 12, rue Louis Blériot • 63017 Clermont-Ferrand Cedex 2 • France

scrip.pharmaintelligence.informa.com 26 April 2019 | Scrip | 5

COMMUNIQUE THEA OPEN INNOVATION AVRIL 2019 ang vok.indd 1 18/04/2019 14:34:39 CLINICAL TRIALS

Lilly/Pfizer’s Tanezumab Safety Takes A Hit With Latest Phase III Results

JOSEPH HAAS [email protected]

li Lilly & Co. and Pfizer Inc.’s efforts to revive the prospects pain patients showed efficacy with a 10 mg dose of tanezumab, of tanezumab – and with it the safety-troubled nerve growth but not a 5 mg dose; safety, however, was deemed acceptable in Efactor (NGF) inhibitor class – endured another setback, as the that study. (Also see “Tanezumab Dances Through Back Pain Stud- two pharmas reported that while their drug hit two of three ef- ies With “Acceptable” Safety Answers” - Scrip, 20 Feb, 2019.) ficacy endpoints in a 16-week analysis in patients, an 80-week safety assessment showed worrisome indications of DEAD COMMERCIALLY, IF NOT YET FROM A disease worsening compared to control. DEVELOPMENT STANDPOINT? In top-line data released after the markets closed April 18, Lilly In an April 18 note, Wolfe Research analyst Tim Anderson declared and Pfizer said a 5 mg dose of tanezumab showed statistically sig- tanezumab effectively dead from a commercial standpoint due nificant improvement in pain and physical function after 16 weeks to its safety issues, even if its development and regulatory fate is in patients with moderate-to-severe osteoarthritis of the hip or not yet sealed. He added that Wolfe has modeled no revenues to knee compared to a control group that received non-steroidal Pfizer or Lilly from the drug, while other estimates have suggested anti-inflammatory drug (NSAID) therapy. Patients’ overall assess- tanezumab could offer blockbuster sales potential in the longer ment of their osteoarthritis with the 5 mg dose of study drug was term if approved. Anderson also suggested that Lilly and Pfizer not significantly different from the control group, however, and seem resigned to moving on from the candidate. a 2.5 mg dose of tanezumab missed all three efficacy endpoints. “The language the companies use in their description of the On an 80-week measure of safety based on joint health out- data is notable for its distinct lack of enthusiasm,” he wrote. “There comes, tanezumab was not as safe as the control regimen by a is a discussion of weighing results and trying to understand them statistically significant margin, the companies announced. Using in the context of the unmet medical need in chronic pain, but a composite measure of rapidly progressing osteoarthritis (RPOA) there is no affirmation that a regulatory filing remains on track.” type 1 or type 2, subchondral insufficiency fracture, osteonecrosis The NGF class overall has a long history of clinical holds due or pathological fracture, the incidence of events was 7.1% in the to neuro-musculoskeletal and joint damage safety concerns, 5 mg treatment arm, 3.8% in the 2.5 mg treatment arm and 1.5% but Pfizer and Lilly revived their development efforts with tan- in the control arm. ezumab in 2015 with a trial protocol they said would offer risk RPOA cases accounted for a significant majority of the events mitigation against joint damage. (Also see “Pfizer/Lilly ready recorded on the composite safety measure, the companies noted: to ditch painful past with new tanezumab trials” - Scrip, 23 Mar, the incidence was 6.3% in the high-dose tanezumab patients; 2015.) In 2018, they reported that the drug met all three ef- 3.2% for the lower dose and 1.2% in the control group. Eighty-one ficacy endpoints in a previous Phase III study in osteoarthritis, percent of the RPOA events were in the type 1 category. but that study’s findings left the safety question unanswered. There was one patient with osteonecrosis in the 5 mg tane- (Also see “Pfizer/Lilly’s Tanezumab Reduces Osteoarthritis Pain, zumab arm, but none in the other two arms. Subchondral insuf- But Is It Safe?” - Scrip, 18 Jul, 2018.) ficiency fractures occurred in seven patients receiving the 5 mg In an April 18 note, SVB Leerink analyst Geoffrey Porges said the dose of the antibody candidate, six patients receiving the 2.5 mg latest tanezumab data might bring about the death knell for the dose and four patients in the NSAID arm. There were no cases of NGF inhibitor class, including a rival candidate, , being pathological fracture in the study. Incidence of total joint replace- developed by Regeneron Pharmaceuticals Inc. and Teva Phar- ment was 8% in the high-dose arm, 5.3% in the low-dose arm and maceutical Industries Ltd. “It is hard for us to imagine how these 2.6% in the control arm. [tanezumab] results could have been much worse,” he said. Overall, patients in the study received tanezumab or NSAID Adding that the Lilly/Pfizer data seem likely to signal a class ef- therapy for 56 weeks to assess efficacy, with an interim look at fect for NGF inhibitors, Porges predicted that Regeneron and Teva 16 weeks and a 24-week follow-up period for safety assessment. will complete their ongoing trials with fasinumab, but “it now Discontinuation rates due to adverse events were higher in the seems likely that their [data safety monitoring board] will apply tanezumab arms than in the control group. There were 10 deaths even more scrutiny to their interim safety analyses, and will have during the study, nine in the treatment arms and one in the con- a low threshold for discontinuing their studies and abandoning trol group; none were assessed to be treatment-related. Half of the target.” the deaths occurred during the treatment period and the other Teva and Regeneron reported modest efficacy success with half during the follow-up period. fasinumab in chronic pain last August, but those findings left The companies said they will review the totality of the data to the safety questions unanswered. (Also see “Regeneron And determine next steps in the development of tanezumab, but at Teva’s Fasinumab Crosses One Threshold; More Remain” - Scrip, least one analyst declared the antibody effectively dead. In Feb- 16 Aug, 2018.) ruary, data from the Phase III TANGO study in chronic lower back Published online 21 April 2019

6 | Scrip | 26 April 2019 © Informa UK Ltd 2019 R&D

Purple Patch For Pharma/Biotech R&D As NAS Launches Reach Record High

ALEX SHIMMINGS [email protected]

o fewer than 68 new active sub- Figure 1: Number of NAS launches by year, 2000–18, with numbers excluding stances were launched in their vaccines also shown first markets in 2018, making it the N 70 most productive year for pharma and bio-

tech this century, new research from Phar- 7 60

maprojects shows. 6 The figure is well up on 2017’s tally of 54, 50

which itself was a vintage year, only trail- 7

ing the previous record year of 2014, when 3 40 3 11 63 novel products reached the market for 6 8 the first time. The overall data point to an 7 30 3

industry that is on an upward trajectory 4 11 on this hard measure of R&D productivity. 20 For the annual review, new active sub- stances (NASs) are defined as novel chemi- 10 cal or biological entities where the active ingredient had received no prior approval 37 57 28 26 31 26 35 36 37 43 34 47 36 29 29 22 26 61 0 37 for human use, and this includes vaccines 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 with novel antigenic component. The list is Other NASs Vaccines therefore a subset of all the first launches Source: Pharmaprojects | Informa 2019 which Pharmaprojects reported during 2018 and excludes the 67 new drug launch- es with reformulated or non-NAS moieties, the precise indications for which they were overactive bladder, were developed in or biosimilars, providing a more stringent approved, their mechanism of action, the partnership with Asian companies, India’s indicator of industry R&D performance. country and month of first launch, and in- Sun Pharma Advanced Research Co. Figure 1 shows the number of NASs dications of whether or not they are first- Ltd. and Japan’s Kyorin Pharmaceutical launched by year for the millennium so in-class, are for rare diseases, and/or had Co. Ltd. and Kissei Pharmaceutical Co. far, revealing just how good a year 2018 orphan drug status. Ltd., respectively. was. The total of 61 non-vaccine NAS The NAS launches were not evenly dis- Eli Lilly & Co., AstraZeneca PLC, No- launches surpassed 2014’s previous re- tributed among the key pharma players, vartis AG and Sanofi each managed two cord by four, and one extra novel vaccine however. Looking at Table 1, which lists the launches, but GlaxoSmithKline failed to debut propelled 2018 even further ahead. top companies by number of NAS launch- produce any. In 2017, the top 10 pharma Indeed, over the past six years pharma has es for all of the top 10 companies, plus any companies brought 21 NASs to market, enjoyed its four highest launch numbers other companies which were involved that figure fell to 19 in 2018. since 2000, clearly showing that R&D pro- in the introduction of more than one Of the six non-top 10 companies who ductivity has entered a purple patch. therapeutic, Pfizer Inc. and Merck & Co. launched more than one NAS, Array Bio- As the 12-month calendar period used Inc. tied, both delivering four new drugs to Pharma Inc. had an outstanding year, in the analysis is somewhat arbitrary the market during the calendar year. producing three new drugs despite only (meaning a few faster-than-expected ap- Pfizer probably edges it, by virtue of ranking at number 153 by pipeline size. provals late in the year can bolster a sin- having originated and developed three Portola Pharmaceuticals Inc. also ex- gle year’s numbers at the expense of its of its novel NASs by itself: Daurismo (glas- celled, achieving two launches out of a successor), it is useful to look at five-year degib), Lorbrena () and Vizimpro pipeline of four products. means. Doing so puts 2014-18’s average (), all for cancer indications. Its over all NASs (including vaccines) at 54.4, one collaboration was with Merck, on the TYPES OF PRODUCTS well ahead of 2009-13’s 41.0 and 2004-08’s antidiabetic Steglatro (ertugliflozin). Examining the NASs by the therapeutic 28.6 – a clear upward trajectory. By contrast, all of Merck’s four drug area of their launched indication, Figure 2 Online can be found a table that pro- launches were developed through col- shows that last year, anti-infectives drew vides a full alphabetical list of the year’s laborations, two of which, the psoriasis with anticancers at the top, with totals of new drugs, along with their trade names, drug Ilumya (til- 17 each, although the anti-infective figure the companies involved in their launch, drakizumab) and Beova (vibegron) for is, as in the preceding year, bolstered by

scrip.pharmaintelligence.informa.com 26 April 2019 | Scrip | 7 R&D

seven vaccines. The report’s author, Ian Table 1: Top Company NAS Launch Performance, 2018 Lloyd, senior director at Pharmaprojects, COMPANY NUMBER OF NAS LAUNCHES 2018 POSITION BY PIPELINE SIZE said, “It’s still another good result for this class though, with antivirals again having Array 3 153 significant success. These included four AstraZeneca 2 4 new HIV therapies, one for hepatitis C, Eli Lilly 2 10 and a rare anti-influenza therapeutic. That leaves four new antibacterials, the best re- GlaxoSmithKline 0 7 sult for this category seen in years.” Ionis 2 34 Anticancers equalled their success in Johnson & Johnson 1 3 2018 compared with the previous 12 Kyowa Hakko Kirin 2 46 months, with 17 NASs, or 24.2% of the Ligand 2 22 NAS launches. This means cancer’s domi- nance of NAS launches is yet to match its Merck & Co 4 8 dominance of the pipeline – 35.2% of the Mylan 2 52 R&D pipeline is currently given over to Novartis 2 1 products for cancer indications – but this Pfizer 4 9 therapeutic area is still outperforming in terms of innovation. Portola Pharmaceuticals 2 1,342 The second largest pipeline therapeu- Roche 1 6 tic area, neurologicals, had a much better Sanofi 2 5 year in 2018. Its six new drugs included Takeda 1 2 three new calcitonin gene-related peptide Source: Pharmaprojects | Informa 2019 inhibitors for migraine prophylaxis, but there were also notable successes in epi- Figure 2: 2018 NAS Launches By Therapeutic Group lepsy and amyloidosis. “Overall, there was a much better therapeutic spread of NAS Sensory 2.90% Respiratory 4.35% launches last year, with winners in every Alimentary/Metabolic 11.59% therapeutic area except the very smallest, Neurological 8.70% antiparasitics,” Lloyd said. Blood & Clotting 7.25% Musculoskeletal 1.45% GEOGRAPHY MATTERS Despite increasing internationalization, Cardiovascular 5.80% the drug industry still primarily launches Dermatological 1.45% its new drugs in the world’s biggest mar- Genitourinary 2.90% ket, the US. In 2018, 41 of the 69 NASs Anticancer 24.64% Hormonal 1.45% made their debut in the US: that equates Immunological 2.90% to 59%, although slightly down on the 63% seen in 2017. “This is on the back of a record-breaking year in approving drugs for the FDA, although it’s notable that Anti-infective 24.64% 2019 started badly with the longest gov- Source: Pharmaprojects | Informa 2019 ernment shutdown in history running on into most of January,” Lloyd said. Japan THE NOVEL NASS OF 2018 is less novelty in our team of new drugs again came in second in 2018, but this 2018 fared well in terms of innovation. this time around,” Lloyd noted. Adding in time doubled the number of first launch- Based on the strict definition of novelty as the cell therapies gives an innovative drug es there to eight from four the previous being the first time a drug with a particu- percentage of 25.0% last year, compared year. Equal third (with Germany) this lar mechanism of action hits the market, with 29.6% in 2017. year was China, which is now matching 2018 produced 15 novel NASs, up from 14 All four of cancer’s innovative drugs its burgeoning R&D field with a genuine in 2017 (although two drugs in 2018 had originally came from specialist compa- presence as a first market to launch in. two novel mechanisms, ensuring that the nies. Array BioPharma and Loxo Oncology Over a third of the new drugs launched new mode of action count was slightly Inc.’s Vitrakvi () is the first TrkA had orphan drug designation for the dis- higher).“This also doesn’t take into ac- inhibitor to hit the market. ease which they were launched for – a count two newly marketed cell therapies, It was approved for use in solid tumors significant proportion, and very slightly which by definition don’t have a specific that have a neurotrophic receptor tyro- up on the previous year’s percentage. pharmacological action. However, given sine kinase (NTRK) gene fusion, making it See Figure 4. that there were more drug launches, there tissue-agnostic.

8 | Scrip | 26 April 2019 © Informa UK Ltd 2019 R&D

Figure 3: 2018 NAS Launches By Country/Region oncological approach induces antitumor cytokines, activates NK cells, suppresses Australia 1 Austria 1 regulatory T-cells and regulates macro- Cambodia 1 Chile 1 phage polarization. It debuted for the China 4 EU 1 treatment of advanced solid tumors, in- Finland 1 cluding lung, breast, liver, colorectal and Germany 4 stomach cancers, in Cambodia. There are Italy 1 plans for western development, and or- phan drug status in the US has already been granted in both hepatocellular car- Japan 8 USA 41 cinoma and pancreatic cancer. A collaboration between Japan’s Kyo- Netherlands 1 wa Hakko Kirin Co. Ltd. and Ultragenyx New Zealand 1 Nordic countries 1 Pharmaceutical Inc. delivered Crysvita Norway 1 Russia 1 (), whose novel mechanism of S Korea 2 Spain 1 action is inhibiting fibroblast growth fac- Thailand 1 tor 23, the first of four alimentary/meta- UK 1 bolic novel NASs last year. The US was Source: Pharmaprojects | Informa 2019 again the first market here, where it was approved for the rare disease X-linked hy- Figure 4: Percentage Of NAS Launches With An Orphan Drug Designation, 2012–18 pophosphatemia in both adult and pedi- 60 atric patients aged one year or older. “The

55 monoclonal antibody is not only the first- 52.2 to-market with this mechanism, it’s the 50 only drug on the entire Pharmaprojects 45 database which we report to work in this way,” Lloyd said. 40 Also emanating from Japan was Ajino- 36.1 37.0 36.8 35 35.2 moto Co. Inc., Mochida Pharmaceutical

30 Co. Ltd. and EA Pharma Co. Ltd.’s Goof- 27.5 27.1 ice (elobixibat), for chronic constipation. 25 This drug has a dual mechanism of action,

20 being an ileal bile acid transport inhibi- tor and sodium/bile acid cotransporter 15 inhibitor, with neither of these activities 10 having been found in a marketed drug before. The former protein absorbs bile 5 acids from the intestinal lumen, bile duct 0 and the kidney, while the latter is a liver 2012 2013 2014 2015 2016 2017 2018 bile acid transporter. Source: Pharmaprojects | Informa 2019 Then there were two new enzyme re- placement therapies: Chiesi Farmaceutici Tibsovo (ivosidenib) was developed by Verastem Oncology’s Copiktra (duvelis- SPA’s Lamzede (velmanase alfa), which is US-based Agios Pharmaceuticals Inc. and ib) is a dual-acting PI3 kinase delta and alpha mannosidase II, and BioMarin Phar- its licensee, the Chinese concern CStone gamma inhibitor, and this is the first time maceutical Inc.’s Palynziq (pegvaliase), a Pharmaceuticals Co. Ltd., and is the first a drug targeting the gamma receptor sub- pegylated phenylalanine ammonia lyase. isocitrate dehydrogenase 1 inhibitor to hit type has been approved for relapsed or the market. It follows on the back of the refractory chronic lymphocytic leukemia, ANTI-INFECTIVES 2017 first-in-class isocitrate dehydroge- small lymphocytic lymphoma and follicu- In the anti-infectives segments, there were nase 2 inhibitor IDHIFA (), also lar lymphoma. two novel anti-infectives. Theratechnolo- from Agios. Both drugs were launched for The final novel NAS in oncology is a gies Inc.’s Trogarzo (ibalizumab) is the first acute myelogenous leukemia, a rare and little different. Chinese company Yisheng in a new class of drugs which inhibit the aggressive cancer which is experiencing a Biopharma’s Yivyka puts together an in- CD4/GP120env interaction, preventing hike in R&D – Pfizer’s Daurismo (glasdegib) activated purified rabies virus with the viral entry. The monoclonal antibody will and Kotobuki Pharmaceutical Co. Ltd./ firm’s proprietary double-stranded RNA- be used as a rescue therapy, for the small Astellas Pharma Inc.’s Xospata (gilteritinib) based toll-like receptor 3 (TLR-3) agonist group of patients who are experience treat- were also launched for the disease last year. adjuvant technology, PIKA. This immuno- ment failure on standard oral treatments. scrip.pharmaintelligence.informa.com 26 April 2019 | Scrip | 9 R&D/FINANCIALS

The second novel anti-infective was for of thrombocytopenic purpura, thrombotic approved for the treatment of complex flu. Shionogi & Co. Ltd. and Roche have and idiopathic. For the former, Ablynx NV perianal fistulae in Crohn’s disease pa- collaborated to bring Xofluza (baloxavir produced the Factor VIII inhibitor nano- tients. The other cell therapy launched marboxil) to the market, first in Japan and body Cablivi (), while the was Chilean company Cells for Cells’ then subsequently in the US. It inhibits idiopathic treatment was Tavalisse (fosta- Cellistem, another allogeneic expanded the CAP-dependent endonuclease, and as matinib disodium), from Rigel Pharma- therapy, here using umbilical cord stem such is the first endonuclease inhibitor to ceuticals Inc., which is the first example of cells delivered intravenously to treat be successfully developed. a Syk tyrosine kinase inhibitor to reach the heart failure and osteoarthritis. Moving to ophthalmology, Spark market (the drug also hits Flt-3). Of the other non-novel MOA NASs, there Therapeutics Inc. and Novartis’s Luxturna The single CNS success in terms of are a few other stand-outs. Two drugs were (voretigene neparvovec) became the first entirely new mechanisms of action pro- launched for transthyretin-related heredi- ever US-approved in vivo gene therapy, duced three new drugs in 2018: the calci- tary amyloidosis: Ionis Pharmaceuticals targeting patients with the ophthalmo- tonin gene-related peptide inhibitors for Inc. and Akcea Therapeutics Inc.’s Tegsedi logical genetic disorder of confirmed bi- migraine prophylaxis. Amgen Inc. and No- (inotersen) was another rare success for allelic RPE65 mutation-associated retinal vartis’s Aimovig (), got there first an antisense therapeutic, while Alnylam dystrophy. It was approved in 2017 but in the US in July, followed a few months Pharmaceuticals Inc. produced Onpattro not launched until May 2018 at a price of later by Eli Lilly’s Emgality () (patisiran), the first RNA interference drug $425,000 per eye, or $850,000 per patient. and Teva’s Ajovy (). to be successfully brought to the market. The other new ophthalmological first- Click here for the full Pharmaprojects in-class product was for the more common OTHER NOTABLES report, Pharma R&D Annual Review 2019 eye disease, glaucoma. Aerie Pharmaceu- Other interesting products to reach the Supplement: New Active Substances ticals Inc. launched Rhopressa (netarsudil), market in 2018 included the cell therapy Launched During 2018. which adds the novel Rho-associated arena, TiGenix NV and Takeda Pharma- Published online 12 April 2019 kinase 2 inhibitor activity to the ways to ceutical Co. Ltd.’s Alofisel (darvadstro- treat this common condition. There were cel), an expanded allogenic adipose-de- To view this story in full including all tables two novel launches for the different forms rived adult stem cell therapy which was please go to: https://bit.ly/2J05pp9 Cassiopea Hails Breezula’s ‘Good Hair Day’ And Plans FDA Talks On Phase III

STEN STOVALL [email protected]

assiopea SPA is to initiate talks with the US Food and Drug product.” She noted that the global hair loss market is very large Administration on Phase III trials in men with Breezula and very underserved, with only OTC products and generic thera- C(clascoterone) and proceed with plans for proof of concept pies available. “Therefore this product, if approved, could serve a studies in women after the topical anti-androgen produced “very global audience,” she added. positive” 12-month Phase II data in males. The double-blind dose-ranging trial evaluated four doses of Final 12-month Phase II data showed Breezula met one of two Breezula: 2.5% twice daily, 5% twice daily, 7.5% twice daily or 7.5% co-primary endpoints, demonstrating statistically significant im- once daily in 400 males with mild-moderate androgenic alopecia. provements in the change from baseline in non-vellus target area Breezula’s benign safety profile was confirmed, with adverse headcount versus placebo, and generated positive trends in the events and local skin reactions similar to placebo, and no treatment second co-primary endpoint of hair growth assessment (HGA). related serious adverse events. Importantly, sub-group analysis Key secondary endpoints were also met, including change from confirmed no systemic effect on cortisol levels, the company said. baseline in non-vellus target area hair width, suggesting Breezula Breezula is a different, higher-strength clascoterone formula- both prevents hair loss and promotes hair growth. tion of Cassiopea’s lead investigational asset Winlevi, which the The 12-month data are largely in-line with prior interim six company hopes will become the first topical anti-androgen drug month results, as the beneficial efficacy is broadly maintained, to be approved for acne. the Swiss-listed company said. “Based on these results, we plan Cassiopea’s pipeline consists of four clinical assets: Winlevi and to meet with the FDA mid-year to discuss the planned six-month CB-06-01 for acne; Breezula for androgenic alopecia; and CB-06- Phase III trials in men,” Cassiopea CEO Diana Harbort said in a state- 02 for anogenital warts. In a reaction note to the 12-month Phase ment when announcing the study’s 12-months data. “Hopefully, II Breezula data, analysts at Jefferies said, “Breezula continues to we will begin our Phase III program in the fourth quarter of 2019.” offer significant optionality, with Winlevi in acne the key value “We also plan to begin, as soon as practicable, a POC study in driver.” They forecast peak US sales for Winlevi of $320m and women, which would enlarge significantly the potential of the $205m for Breezula. Published online 16 April 2019

10 | Scrip | 26 April 2019 © Informa UK Ltd 2019 FINANCIALS

BI Bets On Expanding Jardiance As Diabetes Drug Sales Soar

KEVIN GROGAN [email protected]

oehringer Ingelheim GmbH’s Jardiance consolidated its BI board reviews a strong 2018 performance position as the best-selling diabetes therapy in the selective Bsodium glucose cotransporter-2 (SGLT-2) inhibitor class in 2018 and the German group expects to keep hold of top spot with expanded indications in heart failure and kidney disease. At its annual press conference in Ingelheim on 17 April, the company reported a rise of over 50% for Eli Lilly & Co.- partnered Jardiance (empagliflozin) to €1.5bn, while sales of Synjardy(empagliflozin/metformin) and Glyxambi (empa- gliflozin/linagliptin) added another €300m to BI’s coffers. Speak- ing to Scrip after the results were presented, Allan Hillgrove, head of BI’s human pharma business, noted that the company was continuing to reap the benefits of a label update based on the landmark 7,000-patient EMPA-REG cardiovascular trial, in which Jardiance demonstrated a 38% reduced risk of CV death, a 35% The latter posted 2018 sales of €2.4bn, a decline of 11.4% that reduction in the risk of hospitalization for chronic heart failure was principally driven by generic competition in Europe. Hillgrove and cut the risk of incidence or worsening nephropathy by 39%. said that BI was managing the patent expiry, noting that while That data “at least posed the question on how it looks outside there is “a little bit of price pressure” in some markets Spiriva is diabetes so we thought it was important to go broader,” he said. BI “holding on pretty well,” helped by an encouraging response from began the EMPEROR clinical trial program for chronic heart failure doctors and patients in Europe to the roll-out of the firm’s new- last year, which comprises two Phase III studies in around 7,000 generation inhaler Respimat. patients with and without diabetes. Spiriva lost patent protection in the US last summer but he re- Michel Pairet, BI’s head of R&D, told Scrip that the data from vealed that the product still had no copycat competition there, as it the EMPERIAL exercise capacity trials would be out “in the sum- appears that generics companies have not come up with a soft mist mer, July or August, and we plan a submission for the CHF indi- inhaler like Respimat, making the pathway to approval trickier. Hill- cation this year.” He also referenced the EMPA-KIDNEY program grove would not say when he expected a rival to appear but “I guess in partnership with Lilly, Oxford University, Duke University and economics tells us that at some stage we will have generics enter.” others to study Jardiance in patients with chronic renal disease, As for the anticoagulant Pradaxa (dabigatran), sales were up 7% which is evaluating 5,000 diabetic and non-diabetic patients. to €1.50bn. Hillgrove said there were a number of countries where Data from that program are not expected until 2022 or 2023 the product was performing well “and China growth is still very, and Pairet acknowledged that Jardiance was behind at least one very strong,” as is Latin America. of its SGLT2 competitors for the kidney indication. Last week, However he acknowledged that “our growth hasn’t been as high Johnson & Johnson presented data from the Phase III CREDENCE as the market has been for the whole class, but even in countries study on Invokana (canagliflozin) – which has fallen behind the where the growth slowed down, we’re still seeing growth so Pradaxa class leaders Jardiance and AstraZeneca PLC’s Farxiga/Forxiga will get larger and we’ve still got aspirations for that in the future.” (dapagliflozin) over amputation fears – that showed diabetics Another BI blockbuster, Ofev () for idiopathic pul- with chronic renal disease taking the once-daily pill had a 30% monary fibrosis had 2018 sales of €1.10bn (+29%). The company lower risk of kidney failure, dialysis requirement, transplant or has submitted a applications to the Food and Drug Administra- death than those in the placebo arm. tion and the European Medicines Agency to get approval for the AstraZeneca’s renal outcomes study for Farxiga is expected treatment of interstitial pulmonary diseases in patients with sys- to read out around the end of due in November 2020. Pariet temic scleroderma, a rare disease for which there are no thera- said while EMPA-KIDNEY will come a fair bit later, “I think that peutic options at present. based on the empirical data, we are very confident that they The DPP-4 inhibitor Trajenta/Tradjenta (linagliptin) climbed 9% will be highly convincing and we test in both diabetic and non- to €1.4bn, a decent result given that the diabetes drug that is also diabetic patients.” Hillgrove added that “we think the SGLT2 class partnered with Lilly is still not launched in Germany. The company will continue to grow and we are confident we can maintain our has long been in dispute with the country’s authorities who do number one share” boosted by the indications outside diabetes. It not recognize its advantages over metformin in the price setting also seems highly likely that 2019 will be the year when Jardiance procedure and BI confirmed to Scrip that it has no plans to launch overtakes BI’s chronic obstructive pulmonary disease blockbuster in its home market. Spiriva (tiotropium) as the company’s biggest seller. Published online 21 April 2019

scrip.pharmaintelligence.informa.com 26 April 2019 | Scrip | 11 STRATEGY

J&J’s Spravato’s Star Power Rises While Zytiga’s Sets BRENDA SANDBURG [email protected]

She noted that the company has shown superiority of Tremfya versus Hu- mira (adalimumab) and versus Stelara in patients who are Stelara inadequate responders. In addition, the company recently announced data that shows su- perior efficacy to Novartis AG’s IL-17A inhibitor Cosentyx (secukinumab) on the Psoriasis Area Severity Index at week 48. (Also see “ECLIPSE: J&J’s Tremfya Beats No- vartis’ Cosentyx For Long-Term Psoriasis Clearance” - Scrip, 12 Dec, 2018.) “We now have data out through three years demonstrating real consistency of affect and believe that that’s going to be good for us whether we’re compet- ing versus the IL-17s, whether competing versus the old anti-TNFs, or whether we’re ohnson & Johnson’s antidepressant the time of approval, J&J’s Janssen unit competing against the upcoming IL-23s,” nasal spray Spravato (esketamine) is said Spravato’s wholesale acquisition cost Taubert said. Jbeing administered in as many as 800 will range from $4,720-$6,785 for the one- Cosentyx is the brand J&J is aiming to certified sites six weeks after US FDA ap- month induction phase, followed by a catch. The fight over the market recently proval, the company reported in its quar- range of $2,360-$3,540 for monthly main- extended to court when Novartis sought terly earnings call. tenance therapy. a temporary restraining order to stop Distribution is expected to be tightly J&J’s pharmaceuticals business re- J&J from distributing promotional mate- controlled due to risks of sedation and hal- mained the strongest performing business rial comparing the safety of Tremfya and lucination, but Exec VP, Worldwide Chair- segment in the quarter, fueled by newer Cosentyx. The court ruled a TRO was un- man, Pharmaceuticals Jennifer Taubert drugs even as some mature brands faced warranted. (Also see “Novartis Can’t Halt said during the company’s first quarter generics. Worldwide pharmaceutical sales Janssen’s Promo Comparing Their Psoriasis conference call April 16 that the launch grew by 7.9% to $10.24bn, powered by Drugs “ - Pink Sheet, 5 Mar, 2019.) has gotten off to a strong start. The US double-digit growth from nine key prod- AbbVie Inc.’s competing IL-23 inhibi- FDA approved the drug March 5 with an ucts, including Stelara (ustekinumab) for tor Skyrizi (risankizumab) for treatment enhanced risk Evaluation and Mitigation inflammatory disease, the cancer drugs of moderate to severe plaque psoriasis in Strategy (REMS) that limits its distribu- Imbruvica (ibrutinib) and Darzalex (dara- adults recently received a positive opin- tion and dispensing to certified hospitals, tumumab), and the psoriasis treatment ion by the European Medicines Agency’s pharmacies, and outpatient care centers. Tremfya (guselkumab). Stelara had world- Committee for Medicinal Products for Hu- (Also see “J&J Foresees Broad Insurance wide sales of $1.4bn for the quarter, while man Use (CHMP) and has an FDA user fee Coverage For Groundbreaking Spravato Imbruvica generated $784m and Dar- goal date of April 25. (Also see “AbbVie’s Nasal Spray” - Scrip, 6 Mar, 2019.) zalex brought in $629m. Tremfya, which Skyrizi Poised To Enter Packed Psoriasis “We’ve actually got a number of pa- launched in mid-2017, generated $217m, Market” - Scrip, 4 Mar, 2019.) tients who have actually been dosed putting it on a blockbuster trajectory. with the product and some that actually ZYTIGA, REMICADE SALES have had multiple doses successfully. So, TREMFYA GAINS 6.9% OF US DECLINE we believe that we’re off to a very, very PSORIASIS MARKET J&J said the sales of its top performers strong start with Spravato,” Taubert said. J&J spotlighted the success of Tremfya, were partially offset by declines in Remi- “It is going to be an important growth a first-in-class -23 inhibitor, cade (infliximab) and US sales of Zytiga driver for us.” which has secured a 6.9% share of the (abiraterone acetate) due to biosimilar Indicated for use in conjunction with an psoriasis market in the US. and generic entrants, respectively. oral antidepressant, Spravato is the first “It’s performing really well in the market Sales of Zytiga, an oral once-daily medi- drug approved for treatment-resistant de- and all of our clinical data and compara- cation for use in combination with pred- pression in 10 years. The only other drug tive data continue to reinforce what we’re nisone for treatment of metastatic, cas- approved for the indication is Eli Lilly & seeing as this really being a true leading tration-resistant prostate cancer, declined Co.’s Symbyax (olanzapine/fluoxetine). At brand in psoriasis,” Taubert said. 54.5% in the US, while growing 12.9%

12 | Scrip | 26 April 2019 © Informa UK Ltd 2019 STRATEGY

outside the US. J&J said strong sales growth in Europe and Asia J&J’s consolidated growth was just 0.1% in the quarter, with de- were driven by market growth and share gains primarily from the clines in consumer and medical devices offsetting growth in phar- expanded indication of metastatic high-risk castration sensitive maceuticals. In its January sales and earnings call, the company prostate cancer based on the LATITUDE clinical trial. guided investors to expect operational sales growth (excluding With two infliximab biosimilars on the market in the US, Remi- the impact of currency) of 1% or less in 2019 and a reported de- cade worldwide sales fell 20.6% to $1.1bn versus the prior-year cline in revenues of 0.5% to 1.5% versus 2018 performance, with quarter. Talbert noted that J&J has been able to retain about 92% the pharma division facing more generic and biosimilar competi- of the US volume share of infliximab although at a lower and very tion to Zytiga and Remicade, persistent US pricing pressure and a competitive price in the market. stronger US dollar. (Also see “J&J Expects Persistent Pricing Pressure Exec VP and Chief Financial Officer Joseph Wolk noted that the Into 2019 “ - Scrip, 22 Jan, 2019.) pulmonary hypertension drug Tracleer (bosentan) and multiple The strong pharmaceuticals sales performance led the com- myeloma drug Velcade (bortezomib) will likely face generic com- pany to slightly increase its operational sales forecast but ad- petition later this year. J&J markets Velcade outside the US. The justed earnings per share guidance was slightly narrowed to drug already went generic in the US, where the brand is marketed $8.53 to $8.63. by Takeda Pharmaceutical Co. Ltd.. Published online 16 April 2019 Novartis Secures FDA Priority Review For Brolucizumab Thanks To PRV

JESSICA MERRILL [email protected]

ovartis AG’s brolucizumab for wet competition. It also would be a global for Eylea. (Also see “Novartis Back In AMD age-related macular degeneration opportunity for Novartis, which sells Lu- Game With ‘Potential Blockbuster’ Broluci- N(AMD) could be on the US market centis outside the US, while Roche mar- zumab” - Scrip, 12 Nov, 2017.) by the end of the year after FDA granted kets the drug in the US. Since the completion of those Phase III the biologic license application a prior- Brolucizumab is a VEGF inhibitor like Lu- trials, however, Regeneron has chipped ity review. Novartis used a priority review centis and Eylea, but it may have a dosing away at the potential dosing advantage. voucher (PRV) to expedite the review, the advantage. In two Phase III clinical trials, FDA approved a supplemental BLA for company said while announcing the BLA HAWK and HARRIER, brolucizumab dem- Eylea in August for dosing every 12 weeks was accepted for review April 15. onstrated non-inferiority to Eylea dosed after the first year of treatment. (Also see This is the second PRV Novartis has ben- every 12 weeks versus bi-monthly dosing “Regeneron’s Less Frequent Eylea Dosing efited from recently. The company used Makes Late Sprint Across FDA Finish Line” one for the FDA review of Mayzent (sipon- - Scrip, 17 Aug, 2018.) The drug previously imod), which was approved by FDA for was approved for dosing every four or multiple sclerosis in late March. (Also see eight weeks after the first three monthly “FDA Backs Novartis MS Pill Mayzent With treatments. Nonetheless, labeling does Broad Label” - Scrip, 27 Mar, 2019.) Novar- include the caveat that the 12-week regi- tis had at least two vouchers on hand last men is not as effective as the every eight year, one it gained through the approval week dosing regimen. of Kymriah for a rare pediatric cancer and This is the second PRV The recommended dosing for Lucentis, the other it acquired from Ultragenyx Novartis has benefited meanwhile, is once-monthly, although Pharmaceutical Inc. for $130m. (Also less frequent dosing is allowed after the see “Novartis Stockpiling Priority Review from recently. The first three months, though with a similar Vouchers” - Scrip, 19 Dec, 2017.) caveat about the efficacy. Brolucizumab is poised to be a block- company used one Allergan PLC also is developing an eye buster contender, competing in a cat- for the FDA review of injection, abicipar, and plans to submit egory dominated by Regeneron Phar- a BLA to regulatory authorities in mid- maceuticals Inc.’s Eylea () Mayzent (siponimod), 2019, but the rate of intraocular pressure and Novartis’ own Lucentis (ranibizum- seen in clinical trials has raised questions ab). Brolucizumab represents an oppor- which was approved about its commercial viability. (Also see tunity for Novartis to gain back ground by FDA for multiple “Allergan Improves Safety Of Abicipar, But it lost to Regeneron and extend the life Not Enough Compared To Lucentis, Eylea” - of its ophthalmology franchise as Lu- sclerosis in late March. Scrip, 2 Apr, 2019.) centis could eventually face biosimilar Published online 15 April 2019

scrip.pharmaintelligence.informa.com 26 April 2019 | Scrip | 13 STRATEGY

Asia Begins To See Impact From Roche ‘De-Siloing’ IAN HAYDOCK & ANJU GHANGURDE

oche is now in the implementation stage of a worldwide re- organization program first disclosed last year, which in Asia Rhas so far meant the rationalization of one regional office, among other structural and personnel changes. The moves are part of an ongoing transition and decentraliza- tion process first laid out internally to senior managers in mid- 2018, and that began to take practical effect from the beginning of this year. Strategically, the changes are designed to give individual countries more direct reporting lines and autonomy in decision- making to best meet local needs, as the Swiss giant faces some fundamental shifts both in its business and local operating envi- ronments. Roche has already said it is expecting moderate growth in 2019 before a further pick-up beginning in 2021, as new products be- gin to fill a large potential hole from major expiries for its biolog- Singapore Affected In Roche Asia Restructuring ics-dominated oncology franchise later this year. Blockbuster oncology mainstays Avastin (), The latter grouping was further split into eight major countries, Herceptin () and Rituxan (rituximab) are all likely which report into the head of international, and smaller countries to face US biosimilar competition from the second half. The in seven areas. firm is looking to newer drugs such as Ocrevus (ocrelizumab) As part of this move, one source in Asia told Scrip that resources in multiple sclerosis and Hemlibra (emicizumab; licensed from at the regional area levels within the “group of seven” have been Japanese affiliate Chugai Pharmaceutical Co. Ltd. ) for hemo- reduced in favor of the supra-country structure, leading to a num- philia to help fill the gap. ber of changes in country heads. Its just reported first quarter results came in stronger than ex- A global product strategy group focuses on the “Big 8” (in which pected, with these and other new products surpassing forecasts, China is now included) and the US. and the company raised its sales and core EPS outlook. PERSONNEL CHANGES SINGAPORE STREAMLINING The company has not disclosed how many people globally or in While stopping short of giving specifics about the Asia restructur- Asia have been transferred or lost their positions at part of the ing, Roche in Basel confirmed to Scrip that: “Over the past year we process. As for individual countries in Asia, a source told Scrip that have made changes to our commercial model and how we sup- there have already been changes at the senior management level port our country-level operations.” in the Philippines operation. This has involved simplification of above-country support to Roche in Basel commented that the changes at the country lead- move away from a top-down approach, which in practical terms ership level are “based on retirements and talent development.” has involved the rationalization of some regional offices that had Regionally, Rachel Frizberg was appointed area head for APAC acted mainly as liaison with head office. at Roche in September 2018, after previously being commercial This includes in Singapore, where Scrip understands that the director for Europe for three years. pharma APAC office there (which mainly managed the SE Asia re- Before that, she spent several years as general manager in Hong gion) has been sharply downsized, affecting dozens of jobs, and Kong, where she was also president of the local industry associa- meaning several senior level exits. tion, the HKAPI. Roche explained that: “Specifically, we are focusing on our opera- genomiQa, one of Australia’s leading genomic analysis compa- tions in two areas – international and US, and will be consolidating nies, also announced several months ago that Colin Albert had above country support. Our country-level operations are the most been appointed as CEO. Prior to that he was commercial head of important interface with the patients and customers we serve, and the Asia Pacific region for Roche Pharmaceuticals and regional we believe these changes will make it easier for them [country op- general manager of the Asia Pacific region for Roche Foundation erations] to act and adapt to meet rapidly changing local needs.” Medicine, based in Singapore. With the regional coordination function effectively stripped out, country heads will be able to deal more directly with senior INDIA IMPACT managers globally. Reflecting the corporate line on the changes, Roche India told The global restructuring initiative announced in July 2018 saw Scrip that: “Our goal at Roche is to develop and deliver our break- worldwide pharma operations organized into what some experts through medicines to as many patients as possible. The new af- termed a “cluster” approach, divided into the US and rest of world. filiate model enables Roche to work across various functions and

14 | Scrip | 26 April 2019 © Informa UK Ltd 2019 STRATEGY/LAUNCHES

borders - moving away from a top-down ‘siloed’ approach to become a truly agile, Amgen Launches Evenity For networked organization.” The restructuring appears to have had High-Risk Osteoporosis At $21,900 a positive spin-off for at least one regional company. Roche’s former APAC regional head for Roche Pharma in Singapore, Dr List Price Christiane Hamacher, has joined the In- MANDY JACKSON [email protected] dian firmBiocon Ltd.’s Biocon Biologics India subsidiary as CEO, effective from S FDA approval of Evenity (-aqqg) for osteoporosis in postmeno- March 1. pausal women at high risk for fracture, including women with a prior fracture, In this market, the company also seems Ugives Amgen Inc. an opportunity to redouble past efforts in osteoporosis aware- to be focusing on expanding access and ness as the company launches its newest treatment for the disease, noting that it costs experimenting with new roles, for in- less than competing therapies. stance calling its sales and marketing Evenity was developed in collaboration with UCB SA, but Amgen leads commercializa- personnel “value leads” while the local tion in the US and Japan, while its partner is responsible for sales in other ex-US markets. MD of Roche Pharma India Lara Yumi Tsuji Amgen said on April 15 – less than a week after the drug’s April 9 FDA approval – that Bezerra now holds the position of “chief Evenity is now available for shipment to wholesalers in the US. It also revealed the prod- purpose officer”. uct’s list price of $1,825 per monthly injection administered by a health care professional, Sources in the know said that regional adding up to $21,900 for a full course of therapy, which is limited to one year. value leads in India are expected to build Amgen Executive Vice President, Global Commercial Operations, Murdo Gordon noted team capability and drive value of the in an interview with Scrip that Evenity’s annual wholesale acquisition cost (WAC) is a sig- Swiss multinational’s portfolio, while nificant discount to the WAC prices for other anabolic (-building) drugs, which are implementing state level plans and also approved as 18- and 24-month courses of treatment. partnering with various stakeholders. Gordon said Evenity’s list price for 12 months of treatment is one-third lower than Ensuring delivery on patient-centric the cost of 18 months of treatment with Tymlos (abaloparatide) and half the cost of commitments are part of the core efforts 24 months of the Radius Health Inc. drug. Tymlos, which is an analog of parathyroid of these value leads. hormone-related protein, was approved in 2017 and launched at a WAC of $19,500 Bezerra, in an earlier interview with per year. (Also see “Radius Prices Osteoporosis ‘Blockbuster’ Tymlos To Compete, Grow Scrip, maintained that Roche is looking Market” - Scrip, 1 May, 2017.) at a “completely different” strategy in Evenity’s price also is 64% lower than 18 months of treatment with Eli Lilly & Co.’s For- India, with a thrust towards improving teo (teriparatide), an analog of parathyroid hormone, Gordon said, and 73% lower than patient numbers. Revenue build up, she a 24-months course of Forteo. But, Forteo is expected to see its first generic competition indicated at the time, will then follow. this year. (Also see “Roche India Mandate ‘Com- Amgen and UCB have been working together on a strategy to increase awareness pletely Different’ Says New Head Bezzera” of osteoporosis diagnosis and treatment, because initial awareness of the disease has - Scrip, 8 Apr, 2018.) waned since the launch of older osteoporosis drugs, such as Amgen’s own blockbuster The company hopes India can emerge biologic Prolia (). In the US, the focus is on the 2m women who’ve already as a benchmark for other emerging mar- had a fracture because of osteoporosis, given the low rate of treatment for these patients. kets and “improve the health of people “Only 20% of those women who have a fracture receive any type of treatment post beyond borders.” fracture, so really, the unmet need is high,” Gordon said. “We were pleased with the FDA’s Nonetheless, industry experts with approval; we’re pleased with the product label.” knowledge of the matter claim that there has been significant personnel churn at BLACK BOX WARNING: CV RISK EXCLUDES SOME PATIENTS the India operations over the past couple It’s unclear how many of the 2m women who experience a fracture each year will be eli- of years, although clearly not all of it is re- gible for treatment with Evenity, however, since the drug’s label has a black box warning lated to the current APAC recalibration. noting an increased risk of heart attack, stroke and cardiovascular (CV) death based on It’s not immediately clear if any further findings in the Phase III ARCH clinical trial. (Also see “ARCH CV Signal Scuppers Blockbuster cutbacks are still in the works in India. Hopes For Amgen/UCB’s Evenity” - Scrip, 22 May, 2017.) The restructuring under the wider The warning says that women with a stroke or heart attack in the previous 12 months global restructuring program is not shouldn’t be treated with Evenity and doctors should weigh the drug’s benefit in women confined to Asia, as some European with other CV risk factors. Treatment should be stopped for any patients who experience commercial operations have also been a stroke or heart attack while on Evenity therapy. An FDA advisory committee recom- scaled back and around 300 jobs lost mended approval with post-marketing requirements to study CV risk in January and at US affiliate Genentech Inc. over the Amgen proposed a black box warning to limit those risks. (Also see “Evenity Likely Headed past year or so. For Approval With Amgen’s Proposed Indication, But Postmarketing Requirements Remain Published online 18 April 2019 Unclear” - Pink Sheet, 16 Jan, 2019.) scrip.pharmaintelligence.informa.com 26 April 2019 | Scrip | 15 LAUNCHES

The ARCH study found higher rates of CV events for patients the women seeking treatment with Evenity. “We do discuss new treated with Evenity for 12 months followed by 12 months of innovations in our pipeline with payers, so they were aware of the alendronate versus alendronate alone. Those results eventually approval and we’ve talked to them about the profile of the prod- delayed approval of the product until after Radius’ Tymlos approv- uct since approval,” he said, but couldn’t comment on feedback al. (Also see “US FDA Sends Amgen/UCB Evenity Back With BRIDGE from payers, since contract negotiations are ongoing, so remain Request” - Scrip, 17 Jul, 2017.) Amgen refiled its biologic license ap- confidential. plication with the FDA last year after an external review of CV data “It’s obviously our hope that given this product is really for for the drug. such high-risk patients, given that they’ve already had a fracture Gordon said most postmenopausal women at high risk of frac- despite being on other osteoporosis therapies, and that the re- ture, including women with a prior fracture, will not be excluded quirement for building bone is what people are being treated for, from treatment with Evenity due to their higher CV risk and he we would anticipate that payers would see that as being a good does not expect the black box warning to limit uptake. benefit/risk equation for a high-risk targeted patient population,” He noted that Amgen and UCB have been encouraged by the Gordon said. “I think the price that we’ve just set will further opti- response to Evenity’s data and its approval that they’ve gotten mize our ability to secure broad access.” from doctors, so far. Amgen thinks a once-monthly option administered by a health “I think the osteoporosis-treating community have been wait- care provider could be an advantage over self-administered once- ing for a product like this that they can use to treat many of daily injections, such as Forteo and Tymlos. their patients where they feel that they’ve used everything else “We think a once-a-month visit to a health care professional for and they need to build bone,” he said. “I think that they’re gener- the injection is very manageable,” Gordon said. “The feedback on ally understanding of the label and the patients that should and that from patients and clinicians has been very positive.” To ensure shouldn’t receive treatment with Evenity.” adherence, and given the need to counsel patients with severe Jefferies analyst Michael Yee was generally positive about Eve- osteoporosis and monitor cardiovascular risk, it also could be the nity’s commercial prospects in an April 9 noted even with the preferred approach. black box warning, estimating that it will be a $500m-plus prod- The FDA is requiring Amgen to do a five-year observational uct globally. study of CV risks in patients taking the drug and possibly a follow- “We note despite a boxed warning highlighting the risk of up study depending on those findings. bone cancer, Lilly’s Forteo did over $1.5bn in 2018 and $1.7bn Also regarding Evenity’s in-office administration, Gordon in 2017 in global sales,” Yee wrote. “We appreciate that Amgen noted that from a reimbursement perspective the require- will split profits with UCB and that the launch is likely to take ment for the injection to be delivered by a health care profes- some time.” sional makes Evenity eligible for Medicare Part B coverage at SVB Leerink analyst Geoffrey Porges was less optimistic, saying a lower out-of-pocket cost than a self-administered therapy in an April 9 note that, “There is no doubt that Evenity is the most would have under Part D coverage with higher co-pays and potent anabolic agent for bone, but is also likely to see relatively co-insurance fees. limited use given a target population with significant underlying Overall, Amgen aims to emphasize the cost savings potential of risk for such CV events already” based on the older ages of post- a new bone-building drug like Evenity, which also has some effi- menopausal women. Even so, he estimated global sales could cacy in terms of preventing bone resorption, in regard to reducing reach as high as $700m. fracture-related health care costs. Evenity was approved in Japan in January and it’s under review “If we look at the number of hospital admissions per year in in the EU. (Also see “Japan Approvals Include World Firsts For Ro- the US, we’ve got 432,000 hospital admissions and 180,000 mosozumab, Spinal Injury Cell Therapy “ - Pink Sheet, 16 Jan, 2019.) nursing home admissions every year because of post-meno- Amgen and UCB are working with the European Medicines Agen- pausal fractures,” Gordon said. “You’ve got 2m fractures a cy to address any questions and concerns, but UCB is taking the year and if you do an economic analysis of that that’s $19bn lead on EU regulatory and commercial activities. in related cost.” “Given our aging population in the US, those direct costs could US REIMBURSEMENT DISCUSSIONS UNDER WAY significantly increase by 2025 and go above $25bn,” he added. Gordon noted that in the US Amgen is early in its discussions “We think Evenity is a piece of the solution, but we’re also commit- with payers, but the company believes the $21,900 list price for ted to ensuring better screening and diagnosis of these patients a one-year course of therapy should allow for broad market ac- whether they end up on an Amgen product or not.” cess, including under Medicare Part B, which will cover many of Published online 15 April 2019

’ We are tweeting, liking and sharing the latest industry news and LET S GET insights from our global team of editors and analysts, join us!

SOCIAL @PharmaScrip

16 | Scrip | 26 April 2019 © Informa UK Ltd 2019 HEADLINE NEWS

Scrip Awards 2019

Open for Entries The 15th Annual Scrip Awards Entry deadline: 7 June 2019

4 December 2019 | London Hilton on Park Lane, London www.scripawards.com

Entry and General Enquiries: Lisa Anderberg Tel: +44 (0) 20 7551 9560 | Email: [email protected]

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

Sponsored by Headline Sponsor

scrip.pharmaintelligence.informa.com 26 April 2019 | Scrip | 17

JN1994 Scrip Awards 2019 Open for Entries Advert A4_2.indd 1 2019/04/02 15:37 NASH

NASH News & Notes From The European Liver Meeting JOSEPH HAAS [email protected]

any of the companies develop- MADRIGAL MOVES INTO PHASE ing drug therapies for non-al- III IN NASH Mcoholic steatohepatitis (NASH) In an April 14 summary note from EASL, also are investigating non-invasive ways Jefferies analyst Michael Yee named Mad- to diagnose the disease and its precursor, rigal Pharmaceuticals Inc. and Viking non-alcoholic fatty liver disease (NAFLD). Therapeutics Inc., which are both de- Blood tests or scans are showing some JMP Securities veloping oral thyroid hormone receptor promise to replace liver biopsy as the di- (THR) agonists for NASH, as among the agnostic standard in this setting, but early analyst Liisa Bayko companies to watch behind the first four data are inconclusive on their accuracy. into Phase III – Intercept, Genfit, Gilead The US FDA’s draft guidance for NASH said resmetirom Sciences Inc. and Allergan PLC. Madrigal R&D, issued last December, recommends “offers one of the announced March 28 that it has initiated that drug sponsors work on such diagnos- a Phase III trial of resmetirom (MGL-3196), tic tools because of the burden, expense most compelling its THR selective beta agonist in NASH pa- and potential negative impacts of the tients with F2 or F3 fibrosis scores. current diagnosis process, which requires profiles in the NASH Patients will be randomized 1:1:1 to 80 liver biopsy. (Also see “NASH Drug Devel- field, although it will mg or 100 mg daily of resmetirom or pla- opment Guidance Encourages Sponsors cebo, with a primary endpoint of NASH To Adopt Innovative Trial Designs” - Pink require some patience resolution without worsening of fibrosis. Sheet, 4 Dec, 2018.) Many NASH clinical tri- The first 900 patients to be biopsied after als require each patient to undergo biopsy as top-line results are week 52 of treatment will be the basis for before and at the conclusion of treatment. likely a 2021 event.” the Conshohocken, Pa.-based company’s Intercept Pharmaceuticals Inc. and plan to file for accelerated approval in Genfit SA, two of the most-advanced NASH. Key secondary endpoints in the NASH companies, have included non- study will be reduction of LDL cholesterol invasive diagnosis work in their Phase III ers at the EASL meeting and found that and a one-stage or better improvement in programs. (Also see “NASH Pipeline: Rac- many tests have a high failure rate for fibrosis score. ing To The Finish” - Scrip, 21 Mar, 2019.) diagnosing NAFLD, NASH and measures Madrigal reported last November that Genfit presented data at the European of disease severity. FibroScan has a fail- resmetirom yielded a 49% mean relative Association for the Study of Liver Disease ure rate of about 25.5% in patients with liver fat reduction compared to baseline (EASL) meeting April 10-14 in Vienna sug- body mass indices of 30 or above, he re- in a high-exposure cohort of its Phase IIb gesting the NIS4 blood test can accurately ported in an April 10 note. study and a mean 37% reduction in all diagnose patients with NAFLD scores of “In general, current diagnostic tools patients, compared to an 8% reduction in 4 or higher and significant fibrosis (F2 or are very successful in terms of weeding the placebo arm. The drug also showed higher). The French biotech is partnered out patients who do not have NASH, and lipid-lowering potential. with Covance Inc. on developing a poten- can predict with reasonable certainty SVB Leerink analyst Sarraf wrote March tial diagnostic test for NASH patients that have very severe forms of 28 that Madrigal was raising the bar with Prior to EASL, Intercept Senior VP-Med- NASH, but there is a major unmet need its Phase III design by defining NASH reso- ical Affairs, Safety and Pharmacovigilance in the middle ground of patients that lution as a complete absence of hepato- Gail Cawker told Scrip that she expects fall into the F2-F3 [fibrosis score] range cyte ballooning, minimal lobular inflam- hepatologists will need a variety of meth- of NASH,” Sarraf concluded. For the near- mation (score 0-1), at least a two-point ods ranging from radiographic tests like term, at least, liver biopsy will remain reduction in NAFLD score and no worsen- magnetic resonance elastography (MRE) the standard for absolute confidence in ing of fibrosis. The NAFLD score reduction and FibroScan to blood tests that measure diagnosis, he said. measure is more stringent than NASH- ALT and AST levels to diagnose and moni- Illustrating the issue, the analyst added, resolution metrics used in other studies, tor patient response to therapy. “We’ve are findings that transient elastography – he pointed out. certainly measured a great deal of that the process employed by the FibroScan The secondary endpoints are also key to kind of data,” she said. “If you think about tool – has a predictive value as high as Madrigal’s success, especially since Madri- regular clinical practice, a doctor is never 96.6% in identifying patients who don’t gal also hopes to position resmetirom as going to be doing biopsies as a way of have NAFLD, but a predictive value as a hyperlipidemia therapy. “Hitting either monitoring response and progress.” low as 72.4% for identifying patients with of these endpoints, albeit secondary, will SBV Leerink analyst Pasha Sarraf dis- NAFLD even if they have a high threshold almost certainly differentiate Madrigal cussed the issue with key opinion lead- of liver stiffness. from the pack, consistent with their one-

18 | Scrip | 26 April 2019 © Informa UK Ltd 2019 NASH

two strategy,” Sarraf asserted, noting that an LDL-reduction finding would provide Pfizer Thinks KHK Mechanism Could important differentiation compared to In- tercept’s obeticholic acid (OCA). Work For NASH, Diabetes JMP Securities analyst Liisa Bayko said resmetirom “offers one of the most JOSEPH HAAS [email protected] compelling profiles in the NASH field, -al though it will require some patience as fizer Inc. boasts deep pockets and placebo-adjusted reduction in liver fat top-line results are likely a 2021 event” in R&D expertise in a broad range of from baseline, improvement in a mea- a March 28 note. Ptherapeutic areas, but it generally sure of resistance called HOMA-IR, isn’t regarded yet as one of the big players and a reduction in C-reactive protein that VIKING SHOWING SOLID in non-alcoholic steatohepatitis (NASH). suggests “it was going in the right direc- EFFICACY WITH LOWER DOSES However, the big pharma has four NASH tion in signs of inflammation.” Viking, meanwhile, showed progress candidates in clinical development – each during the EASL meeting for its dose- of which takes a hepatic fat-reduction ap- HOPED FOR LIPID-REDUCING reducing strategy with THR beta agonist proach to the multifactorial disease – and ABILITY NOT SEEN VK2809. (Also see “Viking’s Liver Fat Reduc- has begun talking up its first-in-class, The 75 mg dose did not show a benefit in tion Data Portend A New Competitor In Phase II ketohexokinase (KHK) inhibitor either measure and Birnbaum conceded NASH” - Scrip, 18 Sep, 2018.) In a 12-week, for the disease. that neither dose of ‘5919 showed an abil- 45-patient, placebo-controlled study in Pfizer presented data from a 53-patient ity to reduce LDL cholesterol or triglycer- NAFLD patients with elevated LDL cho- Phase II study of PF-06835919 at the Euro- ide levels as hoped. But the overall profile lesterol, the San Diego biotech reported pean Association for the Study of the Liver of ‘5919 gives Pfizer confidence to take the that all 33 patients who received the study meeting April 10-14 in Vienna, saying the KHK inhibitor forward in larger studies, as drug were deemed responders, with the compound showed potential benefit for both a potential NASH or diabetes thera- drug yielding a median relative reduc- insulin resistance and reduction of inflam- py, with subsequent studies also likely to tion in liver fat (measured by MRI-PDFF) of mation. Morris Birnbaum, the New York investigate doses between the 75 mg and 56.5% (p<0.0001). pharma’s chief medical officer for internal 300 mg range, the exec said. A nine-patient cohort receiving a 5 mg medicine, cautioned Scrip that it is early “The decrease in C-reactive protein daily dose had a composite 53.8% medi- days in testing a brand-new mechanism of really provides an indication that we’re an reduction in liver fat (p=0.0001), while action in NASH, but said these initial find- decreasing generalized inflammation by 10 mg daily (p=0.0004) and every other ings suggest the KHK inhibitor might offer blocking fructose metabolism,” Birnbaum day (p=0.0018) also achieved the primary therapeutic utility in NASH and/or diabetes. said. “That shows that we’re going beyond endpoint of a 30% or greater reduction in KHK inhibition is intended to modulate simply reducing fat and really having a fat from baseline. In an April 11 note, Laid- the effect of fructose in a patient’s metab- more generalized effect on the underlying law & Company analyst Yale Jen called the olism. Pfizer also has an acetyl-CoA-car- pathology that leads to NASH, which is in- 5 mg cohort data “highly encouraging.” boxylase (ACC) inhibitor, PF-05221304, in sulin resistance in abnormal metabolism.” “It is encouraging that the 5 mg results Phase II for NASH, while its GLP-1 receptor As it moves toward initiating a Phase IIb are similar to that of the higher doses,” the agonist PF-06882961 and DGAT2 inhibitor combination study in NASH with Novar- analyst said. “We are also impressed by PF-06865571 are in Phase I. The company tis, Pfizer hopes to see indications its own the safety profile of VK2809, and believe inked a partnership to study Novartis AG’s agents can produce a positive cascade a pristine [cardiovascular] safety profile Phase II FXR agonist tropifexor (LJN452) in of effects that may address the fibrosis could showcase the high specificity of the combination with several of its NASH can- seen in NASH by reducing hepatic fat. But drug.” In the study, cardiovascular adverse didates last fall. the Novartis collaboration is intended to event rates were similar between the pla- “There’s data – some in humans, most in study whether greater benefit can come cebo and treatment arms, Jen noted, and preclinical models – that high fructose can from combining fat-reducing and fibrosis- no changes were seen in cardiovascular cause a bad metabolic state, but the reality reducing mechanisms, Birnbaum said. toxicity markers. is that exactly which adverse metabolic pa- “Why we’re looking for collaborators like SVB Leerink’s Sarraf wrote April 12 that rameter fructose alters has really been a bit Novartis, even though we believe our anti- despite the small size of the study, the mysterious and controversial,” Birnbaum steatotics will eventually reverse fibrosis findings should drive Viking to test the said. “It depends on the experiment.” to a certain extent, [is that] having a direct efficacy of even smaller doses of its drug, Some of the data from the PS-110 anti-fibrotic obviously would speed up such as 1 mg and 2.5 mg. “This provides study that tested 75 mg and 300 mg the process and be much more effective,” an additional favorable risk-benefit profile doses of the KHK inhibitor ‘5919 against he said. “We’re certainly on the lookout for and great optionality for patients and phy- placebo in a six-week treatment duration other mechanisms, both internally and ex- sicians if approved,” he said. are encouraging, he added, but not con- ternally, that address inflammation and to clusive because of the size and length of a certain extent fibrosis.” Published online 16 April 2019 the trial. The 300 mg dose showed a 19% Published online 15 April 2019 scrip.pharmaintelligence.informa.com 26 April 2019 | Scrip | 19 NASH

Gilead Increasingly Focused On Combo Therapy In NASH JOSEPH HAAS [email protected]

hile combination therapy ultimately is expected to rule SELONSERTIB/OZEMPIC COMBO WOULD SEEM A the day in non-alcoholic steatohepatitis, much of the LOGICAL APPROACH Wcurrent focus is on which individual drug will be first to A lot is being read into the combination components selected market for the unmet medical need. For Gilead Sciences Inc., how- by Gilead and Novo Nordisk. In a same-day note, Jefferies ana- ever, disappointing results with its NASH candidates to date – and lyst Michael Yee emphasized that the collaboration does not previous success with combo therapy in HIV and hepatitis C – ap- include selonsertib, even though an ASK1 inhibitor “is actually pear to have it looking ahead to combination regimens for NASH. supposed to be the most antifibrotic and the one you’d want to Following February’s Phase III trial failure with its apoptosis- combine a GLP1 with.” He added that “expectations [are] very signaling kinase 1 (ASK1) inhibitor selonsertib, which failed low” for selonsertib. to meet statistical significance for fibrosis reduction in NASH In a statement announcing the partnership, Gilead said patients with cirrhosis (F4), Gilead got some positive attention working in NASH with Novo Nordisk would combine the Dan- at the European Association for the Study of the Liver (EASL) ish firm’s “broad expertise related to diabetes and metabolism” meeting April 10-14 with promising proof-of-concept data for with Gilead’s knowledge of liver disease and combination the combination of Phase II candidates cilofexor (GS-9674) and therapy. The two also plan to explore preclinical research to firsocostat (GS-0976) in NASH. Selonsertib is slated to report better understand the nature of NASH. The collaboration also data from another Phase III trial in patients with bridging fibro- reflects the growing view of the hepatology field that com- sis (F3) during the second quarter, and it also is being investi- bination therapy will emerge longer-term as the standard of gated along with cilofexor and firsocostat in the Phase II ATLAS care in this multi-factorial disease setting. “The takeaway from combination study. EASL so far is some drugs will work (e.g., Intercept), but ulti- On April 12, Gilead also announced a clinical trial collabora- mately various combinations could emerge down the road to tion in NASH with diabetes specialist Novo Nordisk AS. Details further improve efficacy,” Yee commented. are scant on the planned study, which will test Novo’s GLP-1 “This [deal] is smart and generally makes sense as Gilead has analog Ozempic (semaglutide) in combinations with cilofexor consistently stated the combo approach will be best given NASH and firsocostat. While Ozempic is the only type 2 diabetes drug is a complicated disease and KOLs [key opinion leaders] have said to reach Phase II in NASH, a number of candidates are being in- antifibrotic drugs (e.g., FXR which has derisked fibrosis benefit af- vestigated simultaneously for NASH and diabetes because the ter Intercept’s positive Phase III) should definitely look to combine two diseases have similar causality from metabolic dysfunction. with metabolic mechanisms,” he added. Furthermore, NASH is a multifactorial disease, thus the push for He also predicted that this tie-up likely means Gilead won’t pur- combinations that target the metabolic effects along with in- sue NASH-driven M&A activity in the short term. Gilead memorably flammation and fibrosis. took charge of the competitive hepatitis C space with an eyebrow- That the agreement with Novo Nordisk – to test the potential of raising but ultimately well-valued $11bn buyout of Pharmasset a metabolic therapy with compounds that might lessen fibrosis Inc. and then Phase II HCV candidate sofosbuvir back in 2011. So- and/or inflammation – does not include investigation of combina- fosbuvir (Sovaldi) became the backbone of several HCV combina- tion therapy with selonsertib might indicate declining confidence tion therapies that yielded tens of billions in sales to Gilead. by Gilead in that molecule’s future prospects. Analysts frequently “The deal probably means Gilead won’t be acquiring any mid- predict that STELLAR-3, the Phase III monotherapy study in less or late-stage NASH company in the near-term as they want to severely ill patients, is unlikely to succeed. see how combos of their FXR/ACC look at year-end first – plus “This likely reflects pessimism that selonsertib will yield any suc- want to see some of the combo data with Novo Nordisk too cessful results in the Phase IIb combination trial or in the Phase before they go after mechanisms with diabetes and metabolic III trial in F2-F3 patients,” Datamonitor Healthcare analyst Hannah mechanisms,” Yee said. Longer-term, however, the analyst thinks Cohen told Scrip. “Not only did selonsertib fail to show efficacy in acquisition of other NASH assets is likely once Gilead leadership F4 NASH patients, it also produced disappointing results in Gil- has assessed the field. ead’s Phase IIa combination trial.” At EASL, Gilead presented data from a 20-patient, 12-week Those data and the previous Phase III failure “contribute to study of the cilofexor/firsocostat combo that showed improve- doubt that that selonsertib will show histological improvements ment in hepatic steatosis, liver stiffness, liver biochemistry and in its Phase III trial in F2-F3 NASH patients,” she added. serum fibrosis markers. A decline of 30% or more in liver fat from The Gilead/Novo tie up will instead test Ozempic – a GLP-1 baseline measured by MRI-PDFF (magnetic resonance imaging- agonist also in development for obesity – with firsocostat, an proton density fat fraction) was seen in 74% of patients, the com- acetyl-CoA-carboxylase (ACC) inhibitor, and cilofexor, a farne- pany reported. In liver biochemistry, the study showed a median soid X receptor (FXR) agonist. Cilofexor targets the same mech- relative reduction of 37% in alanine aminotransferase (ALT) and anism as Intercept Pharmaceuticals Inc.’s obeticholic acid 32% in gamma glutamyl transferase (GGT). The drugs were well (OCA), widely expected to be the first drug to obtain approval tolerated, Gilead said, with no reports of pruritus, a frequent side to treat NASH patients. effect seen with Intercept’s OCA.

20 | Scrip | 26 April 2019 © Informa UK Ltd 2019 NASH/EXECUTIVES ON THE MOVE

SHORT-TERM DATA PROBABLY MEANINGFUL, But the bigger inflection point for Gilead’s NASH aspirations is BUT NEEDS LONGER-TERM VALIDATION data from the Phase IIb ATLAS study, a seven-arm study investi- In an interview from the meeting, Gilead VP-Fibrosis Clinical Re- gating selonsertib, cilofexor and firsocostat monotherapy as well search Lead Rob Myers called the data “exciting” but cautioned as all of the two-drug combination regimens possible from those that they need to be confirmed in longer-term testing, including three compounds. It is expected to report out data before the end histological data from liver biopsies, which were not part of the 12- of 2019, but probably too late for a presentation at the American week study. “We weren’t particularly surprised by those results,” he Association for the Study of Liver Diseases meeting in November, said. “We’ve previously seen with ACC monotherapy that we had Myers said. significant fat reduction. The data in combination with cilofexor Gilead will decide on what regimen to take forward into Phase are better than that, and that’s what we expected.” III based on the ATLAS results, he said. “When we have the ATLAS With programs moving toward approval in NASH using surro- data available at the end of the year, we want to choose one regi- gate Phase III endpoints for reduction of fibrosis and/or resolution men to take forward into Phase III,” he explained. “We expect that of NASH, it’s not entirely clear yet what findings will prove clinical- to be a combination regimen but we really need to confirm that ly meaningful in NASH patients. But Myers said the findings from based on the data. We’re waiting for the data and we’ll make an the two-drug combo study are likely to lend themselves to better evidence-based decision once the data are available.” liver health outcomes. He didn’t rule out selonsertib being part of a combination “I’d say all of those endpoints are clinically important,” he assert- regimen that advances, saying that the Phase III STELLAR-4 trial ed. “We think that liver fat drives the inflammation and the fibrosis should be seen as more than simply a failure. that is characteristic of this disease, so we think that if we reduce “Certainly, those weren’t the results we were hoping for, but first liver fat we should see downstream benefits in terms of fibrosis. of all we’re learning a lot by digging into the data, learning a lot So, I think those reductions are valuable.” about placebo responses in NASH, about the natural history of “I think the improvements in liver biochemistry also are clini- NASH,” the exec noted. “Although seemingly the study could be cally relevant,” he continued. “At the end of the day, what causes viewed as a failure, we certainly don’t see it that way because it’s complications in these NASH patients is fibrosis, so the fact that teaching us a tremendous amount. Targeting patients with cir- we’ve seen improvements in serum biomarkers of fibrosis and rhosis is a high bar; these patients have significant fibrosis and to then liver stiffness by MRE elastography suggests that we may be regress that over one year was always going to be challenging.” seeing an anti-fibrotic effect.” Published online 13 April 2019 Janssen India MD To Depart ANJU GHANGURDE [email protected]

anssen India chief Sanjiv Navangul is moving on after an eventful stint at the helm of the US multinational’s operations Jin India. Sarthak Ranade, who has been with Janssen for over a decade in various leadership positions, will succeed Navangul as managing director of Janssen India. Navangul, who has been managing director of Janssen In- dia since 2013, steered the launch of key products from the US parent’s stable including Invokana (canagliflozin) and Sir- turo (bedaquiline) onto the Indian market. Growth at John- son & Johnson’s Indian arm is believed to have been robust during his six-year tenure, though specifics around the num- Significant leadership changes bers could not be immediately ascertained since J&J is not are underway at J&J INDIA listed in India. With pricing always a tricky issue for innovator firms in emerg- ing markets, Navangul has been careful to position J&J’s prod- Microbial Technology (IMTECH), a research institute of India’s ucts as being “responsibly” priced in India. For instance, Invokana Council of Scientific and Industrial Research (CSIR). The alliance which was launched in 2015, came at a daily therapy cost of INR51 with IMTECH was aimed at exploring “more effective, safer, all-oral ($0.8 at the time), comparable with some newer treatment op- treatment regimens” for multidrug-resistant TB (MDR-TB) and also tions available in the country and at a fraction of the product’s US developing new molecular entities to treat all TB patients. cost which was then said to be in the region of around $8.77 per pill (wholesale price). NEW MD TO TAKE OVER IN MAY Navangul, a former managing director in the Philippines for Johnson & Johnson confirmed the leadership change at Janssen Merck Sharp & Dohme Ltd. (MSD), is also believed to have played India and said that Navangul will leave employment of Johnson a role in cementing J&J’s 2017 partnership with the Institute of TURN TO PAGE 23 scrip.pharmaintelligence.informa.com 26 April 2019 | Scrip | 21 Pipeline Watch - 12-18 April 2019 Phase II

Search

Change Lead LOA Event Type Drug Name Indication Comments To LOA Company/Partner (%) (%) Phase IIb Diabetes Type 2, DPO-203; Reduced Updated Opko Health OPK-88003 0 23 Obesity HbA1c, Weight Results Phase IIb ENCORE-PH; Non-Alcoholic Updated Novartis AG emricasan Supports Further 0 10 Steatohepatitis Results Studies Phase IIb Mirum ICONIC; Updated Pharmaceuticals maralixibat Alagille Syndrome Encouraging 0 21 Results Inc. Results w/selonsertib + Phase IIa Non-Alcoholic GS-0976; Updated Gilead Sciences cilofexor 0 24 Steatohepatitis Encouraging Results Results w/selonsertib + Phase IIa Gilead Sciences, Non-Alcoholic GS-9674; Updated �rsocostat 1 26 Inc. Steatohepatitis Encouraging Results Results Phase IIa Primary Biliary Encouraging Updated Gen�t SA ela�branor 0 23 Cholangitis Results Results Phase II PF-06482077, 20-valent S pneumoniae Adults (60-64 y/o); Updated P�zer Inc. 0 61 vaccine Pneumonia Immunogeneic Results Phase II Entasis Urinary Tract Updated ETX2514 E�cacy Shown 0 62 Therapeutics Infections Results Progressive Phase II Mirum Familial INDIGO; Reduced Updated Pharmaceuticals maralixibat 0 24 Intrahepatic Symptoms Results Inc. Cholestasis Phase II Alnylam ALN-GO1-002 Updated Pharmaceuticals, lumasiran Hyperoxaluria (OLE); Oxalate 0 62 Results Inc. Reduced Phase II S Aureus CF-301-102; Updated ContraFect Corp exebacase (CF-301) 0 28 Bacteremia Positive Data Results Phase II Androgenetic Improved Hair Updated Cassiopea SpA Breezula (clascoterone) 0 25 Alopecia Growth Results Phase II STEMTRA; Sumitomo Traumatic Brain Updated SB623, cell therapy Improvements 0 19 Dainippon/SanBio Injury Results Observed Phase I/IIa Arrowhead AROHBV1001; Updated JNJ-3989, RNAi Hepatitis B 0 29 Pharma/J&J E�cacy Signs Results Phase I/IIa Myonexus Muscular Encouraging Updated Therapeutics MYO-101, gene therapy 0 26 Dystrophy Results Results (Sarepta) Phase I/II Orchard TIGET-BTHAL; Updated Therapeutics OTL-300, stem cell therapy Thalassemia Proof-Of-Concept 0 30 Results Limited Achieved Phase IIb Emergent Chikungunya Top-Line Chikungunya Vaccine Promising Results 0 27 BioSolutions/NIH Infection Results Phase IIa Promethera Acute-On-Chronic HEP101; Early Top-Line HepaStem 00 Biosciences Liver Failure E�cacy Signal Results Phase IIa Study 201, 202; Assembly Top-Line ABI-H0731 Hepatitis B Encouraging -2 25 Biosciences, Inc. Results Results Phase II Top- Albireo Pharma, Alagille Syndrome, Reduced Serum A4250 00 Line Results Inc. Biliary Atresia Bile Acids, Pruritus Phase II Top- Axsome AXS-05 Smoking Combination 1 18 Line Results Therapeutics, Inc. (bupropion/dextromethorphan) Cessation Showed Bene�t Phase IIa Auto-Antibody Berlin Cures Trial BC007,ssDNA Assoc. Heart In 20 Patients 0 0 Holding AG Initiation Failure Spring Bank Phase II Trial CATALYST 1, 2; Pharmaceuticals, inarigivir Hepatitis B 0 29 Initiation Global Trials Inc. Phase II Trial w/SOC; A Zymeworks, Inc. ZW25 Gastric Cancer 4 10 Initiation Bispeci�c Antibody Phase I/IIa Antibody-Derived Trial FunPep Co., Ltd. FPP003 Psoriasis 00 Peptide Initiation PIPELINE WATCH Phase I/IIa Precision Acute Lymphocytic Gene-Edited CAR-T Trial BioSciences PBCAR0191 10 10 Leukemia, NHL Cell Therapy Scrip’sInitiation weekly Inc./ServierPipeline Watch tabulates the most recently reported Phase I/IIa Mesothelin-Click here for the entire pipeline late-stage clinicalHarpoon trial and regulatory developments from the more Trial HPN536 Solid Tumors Targeted T-Cellwith added10 commentary: 10 than 10,000 drugTherapeutics candidates currently under active research worldwide. Initiation Engager http://bit.ly/2mx4jY3 Phase III PIPELINE WATCH, 12–18 APRIL 2019 Search

Change Lead LOA Event Type Drug Name Indication Comments To LOA Company/Partner (%) (%) Phase III COTEZO IMblaze370 Colorectal Published Roche Holding AG Tecentriq (atezolizumab) (w/); The 0 28 Cancer Results Lancet Oncology, 16 April Phase III HAVEN 4; The Lancet Published Roche Holding AG Hemlibra (emicizumab) Hemophilia A 0 100 Hematology, 16 April Results Phase II/III DELIGHT; The Lancet Diabetes Type Published AstraZeneca/BMS Farxiga (dapagli�ozin) Diabetes & Endocrinology, 0 100 2 Results 13 April Phase III TRACON TAPPAS (w/); TRC105 (carotuximab) Angiosarcoma -35 0 Suspension Pharma/Santen Futility At Interim Analysis Phase III ALKS 3831 ENLIGHTEN-2; Reduced Updated Alkermes plc Schizophrenia 0 57 (olanzapine/samidorphan) Weight Gain Results Phase III Intra-Cellular Long-Term Safety (Switch Updated lumateperone Schizophrenia 0 81 Therapies, Inc. Study); Favorable Results Results Phase III Diabetic CREDENCE; Reduced Renal Updated Johnson & Johnson Invokana (canagli�ozin) 0 99 Nephropathy Failure Risk Results Phase III Ventilated Merck & Zerbaxa ASPECT-NP (vs Updated Nosocomial 0 96 Co./Astellas (ceftolozane/tazobactam) meropenem); Non-Inferior Results Pneumonia Phase III Ameluz (5-aminolevulinic Actinic Phototherapy; Lesions Updated Biofrontera AG 0 100 acid) Keratoses Cleared Results Phase III Fungal Updated Scynexis, Inc. ibrexafungerp Infections, FURI; Favorable Responses 0 63 Results Refractory Phase III Spinal STR1VE; Encouraging Updated Novartis AG Zolgensma gene therapy Muscular 0 99 Results Results Atrophy Leber's Phase III GenSight Biologics Hereditary RESCUE; Positive At Week Updated GS010, gene therapy 2 47 S.A. Optic 72 Results Neuropathy Phase II/III Stealth Barth TAZPOWER; Positive Updated BioTherapeutics elamipretide 0 40 Syndrome Results Results Inc. Phase III Candida auris CARES; EncouragingSource: Biomedtracker | Informa, 2019 Top-Line Scynexis, Inc. ibrexafungerp 1 63 Candidemia Results Results 22 | Scrip | 26 April 2019 © Informa UK Ltd 2019 Phase III vs. NSAIDs; Met Two Of Top-Line P�zer Inc./Eli Lilly tanezumab Osteoarthritis Three Co-Primary -13 52 Results Endpoints Phase III Atopic Top-Line Galderma S.A. nemolizumab Achieved Primary Endpoint 2 26 Dermatitis Results Phase III Alnylam ILLUMINATE-B; Global Trial Pharmaceuticals, lumasiran Hyperoxaluria 0 62 Pediatric Study Initiation Inc. Phase III CStone GEMSTONE-303; A anti- Trial Pharmaceuticals CS1001 Gastric Cancer 0 PD-L1 Antibody Initiation (Suzhou) Co., Ltd Phase II/III Leber's ProQR Therapeutics ILLUMINATE; An RNA Trial sepofarsen (QR-110) Congenital 27 57 N.V. Therapy Initiation Amaurosis Phase II/III Alzheimer's GAIN; In Mild To Moderate Trial Cortexyme, Inc. COR388 42 52 Disease Disease Initiation Approvals

Search

Event Type Lead Company/Partner Drug Name Indication Market Comments Accelerated Bladder Johnson & Johnson Balversa (erda�tinib) US First FGFR Kinase Inhibitor Approval Cancer AbbVie/Boehringer Skyrizi Moderate To Severe Approval Psoriasis Canada Ingelheim (risankizumab) Disease

Source =Biomedtracker; LOA = Biomedtracker's opinion on likelihood of approval. EXECUTIVES ON THE MOVE

CONTINUED FROM PAGE 21 tend the monopoly rights on bedaquiline from 2023 to 2027. J&J & Johnson Pvt Ltd (the India operating company) on April 30 to has refuted these claims. J&J has donated over 10,000 courses of pursue “other opportunities”. bedaquiline in 2016 as part of a global donation program, op- The company said that Sarthak Ranade would take charge as erated in partnership with the US Agency for International De- managing director, Janssen India, and member of the Janssen velopment (USAID), to support and enable the Government of Asia Pacific leadership team effective May 1, 2019. India to build capacity for the medicine’s introduction. Recently, Sarthak, who joined Janssen in 2007, has held senior commer- Janssen said it would provide an additional 10,000 courses of cial roles in India, Japan and at the regional level in Asia Pacific. Sirturo free of charge through USAID to India. Most recently, he was vice president, commercial operations for Janssen India. COMPENSATION MAELSTROM “We are confident that under Sarthak’s leadership, Janssen will Much of the spotlight in India, however, has been on the con- continue to deliver innovative medicines to address the unmet troversy over compensation payable to Indian patients who had medical needs of Indian patients,” J&J told Scrip. received J&J’s DePuy unit’s faulty ASR hip implants. J&J has chal- Ensuring a steady flow of innovative products from the US par- lenged the government’s formula for determining compensation ent, despite the multiple challenges and limited pricing leverage and the matter is in court. The company has claimed that the gov- in markets like India is something Ranade will need to keep his ernment has no jurisdiction under India’s Drugs and Cosmetics focus on, some industry experts suggested. Act or the rules to fix such compensation. Significantly, there has been top level personnel movement in INDIA MARKET SIMMERING ISSUES the devices segment as well in India. J&J confirmed that Raghav- Ranade’s appointment also comes at a time when J&J has in gen- endra Shenoy has been appointed managing director of Johnson eral been in firefighting mode in India on multiple issues, largely & Johnson Medical India, while previous head, Sushobhan Das- led by those pertaining to its faulty hip implants. gupta, has moved into an “expanded role” as VP, orthopedics, On the pharma front, public health activists and the humani- Johnson & Johnson Asia Pacific. Dasgupta serves on both the tarian group Médecins Sans Frontières have been pushing for orthopedics global leadership team and the Asia Pacific medical halving of the price of Sirturo to no higher than $32 per month. devices leadership team. “As the regional leader, Sushobhan will Two TB survivors have also challenged J&J’s patent application continue to support key orthopedic matters in India, including for a salt form of bedaquiline in India that they claim could ex- ASR,” J&J clarified. Published online 17 April 2019 Company Move APPOINTMENTS Search

Effective Executive To Company New Role From Company Previous Role Date Roland Vice President, Drug Head, Medicinal Chemistry, Cerevance Inc AstraZeneca, UK 4/16/19 Burli Discovery Neuroscience GW Executive Vice President, Darren Pharmaceuticals Chief Commercial O�cer, US Seattle Genetics Commercial and Member, 4/22/19 Cline plc Executive Committee Beni B. KSQ Blueprint Senior Vice President, Clinical Chief Medical O�cer 4/16/19 Wolf Therapeutics Medicines Development Samia MC2 Executive Vice President, Speci�c Pharma Chief Executive O�cer 4/4/19 Kappe Therapeutics Sales and Marketing, Europe AS Senior Vice President, Barry MetrioPharm AG Strategy and Business Frankel Group llc Founder 4/10/19 Frankel Development Aerpio Steve Chief Medical O�cer and REGENXBIO Inc Pharmaceuticals Chief Medical O�cer 4/17/19 Pakola Senior Vice President Inc Head, Research and Giles Silence Development and Chief Albumedix Chief Medical O�cer 6/1/19 Campion Therapeutics Medical O�cer Fairooz Senior Vice President, Tocagen Genentech Principal Medical Director 4/15/19 ClickKabbina here forv arall appointments: https://bit.ly/2oHWRYnClinical Development Source: Medtrack | Informa, 2019 scrip.pharmaintelligence.informa.comPromotion 26 April 2019 | Scrip | 23

Search

Effective Executive To Company New Role Previous Role Date Alphatec Holdings Executive Vice David Sponsel Area Vice President, West 4/15/19 Inc President, Sales Patrick J Cerecor Inc Chief Strategy O�cer Vice President, Business Development 4/15/19 Crutcher Carmen Vice President, Medical Chiesi USA Inc Senior Director, Medical Affairs 4/16/19 Dell’Anna Affairs Andrew G. INSYS Chief Executive O�cer Chief Financial O�cer 4/15/19 Long Therapeutics Inc Head, Corporate Development and Interim Chief John Trzupek KSQ Therapeutics Chief Business O�cer 4/16/19 Financial O�cer Director

Search

Executive To Company New Role Effective Date Anne Phillips AMAG Pharmaceuticals Inc Director 4/12/19 Kathrine O'Brien AMAG Pharmaceuticals Inc Director 4/12/19 George Milne, Jr. Aurinia Pharmaceuticals Inc Chairman 4/29/19 Simon Pedder Cerecor Inc Executive Chairman 4/15/19 Amit K. Sachdev Eiger BioPharmaceuticals Inc Director 4/15/19 Glenn Dubin Frequency Therapeutics Director 4/4/19 Marijn Dekkers Ginkgo Bioworks Chairman and Strategic Advisor 4/16/19 W. Mark Watson HedgePath Pharmaceuticals Inc Chairman 4/15/19 Paul Edick Milestone Pharmaceuticals Inc Chairman 4/16/19 Samuel Broder Sensei Biotherapeutics Director 4/15/19 Masaru Onishi Teijin Ltd Director 6/20/19 Lori Kunkel Tocagen Director 4/15/19 Advisor

Search

Executive To Company New Role Effective Date Lori Kunkel Rain Therapeutics Scienti�c Advisory Board Member 10/1/19 Alain Algazi Sensei Biotherapeutics Immuno-Oncology Advisory Board Member 4/11/19 Daniel H. Sterman Sensei Biotherapeutics Immuno-Oncology Advisory Board Member 4/11/19 Robert Pierce Sensei Biotherapeutics Immuno-Oncology Advisory Board Member 4/11/19 Robert Schreiber Sensei Biotherapeutics Immuno-Oncology Advisory Board Member 4/11/19 Saar Gill Sensei Biotherapeutics Immuno-Oncology Advisory Board Member 4/11/19 Sara Pai Sensei Biotherapeutics Immuno-Oncology Advisory Board Member 4/11/19 Other

Search

Executive From Company Previous Role Effective Date Move Type Peter Greenleaf Cerecor Inc Chief Executive O�cer and Director 4/15/19 Resignation Saeed Motahari INSYS Therapeutics Inc President and Chief Executive O�cer 4/15/19 Resignation Brought to you by Headline sponsor Sponsored by

Citeline Excellence Awards | 2019 Pharma intelligence |

CLINICAL & RESEARCH EXCELLENCE AWARDS 2019 May 2, 2019 Hyatt Regency Boston, Boston, MA

BOOK YOUR TABLE NOW!

www.clinicalresearchexcellence.com

General Enquiries: Jo Kirkpatrick | Tel: +44 (0) 20 7017 7180 | Email: [email protected]

JN0000 CARE Awards 2019 Book Now Advert A4.indd 1 2019/01/14 13:15