China Surprises With First CRISPR INFOGRAPHIC: The Growth Of A Giant Expert View Trial Despite Regulatory Lag As Teva and Allergan close the The European Commission is looking The lack of a comprehensive regulatory largest generics deal in history, to boost confidence in biosimilars to pathway has not hindered Chinese review their M&A journeys for the support their uptake on a much wider researchers from initiating first human last two decades (p16) scale across Europe (p20) trial using CRISPR technology (p10)

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Scripscripintelligence.com Pharma intelligence | informa day include Pfizer’s SAM-531 (suspended in 2012) and AbbVie Inc.’s ABT-354 (sus- pended in 2014). The PF-05212377 failure raised ques- tions about future prospects for others in the 5-HT6 class. Lundbeck’s idalopirdine (Lu AE58054), licensed from Eli Lilly & Co. and partnered with Otsuka Pharmaceutical Co. Ltd., and Axovant Sciences Ltd.’s RVT-101, obtained very cheaply from GlaxoSmithKline PLC for $5m in 2014, are both in Phase III. Performance of Pfizer’s 5-HT6 antagonist PF-05212377 was numerically worse than placebo in Phase II. Suven Life Sciences Ltd.’s SUVN-502 and Avineuro’sAVN 101 are in Phase II.

THE DISAPPOINTING Shutterstock: ThitareeS Shutterstock: PFIZER DATA Results from the failed Phase II study of PF- 05212377 were presented in a poster on Pfizer’s Failed 5-HT6 Alzheimer’s July 24 at the AAIC meeting, held in Toronto. The 18-week study randomized patients with mild-to-moderate Alzheimer’s disease Drug Leaves Hope For Class and neuropsychiatric symptoms to the test EMILY HAYES [email protected] drug with Eisai Co. Ltd./Pfizer Inc.’sAricept (donepezil) or donepezil with placebo and Presentation of data at Alzheimer’s As- Antagonists against 5-HT6 are part of an assessed improvements after 12 weeks on sociation International Conference high- emerging oral class of drugs that have shown treatment. The trial’s primary endpoint was lights failure of Pfizer’s 5HT6 antagonist modest efficacy in mid-stage studies for re- improvement on the Alzheimer’s Disease PF-05212377, while still leaving room to lieving symptoms of Alzheimer’s disease. Assessment Scale-Cognitive Subscale at 12 hope for others in class like Lundbeck’s In a therapeutic area marked by trial weeks from baseline (ADAS-Cog 13) and idalopirdine and Axovant’s RVT-101 failure, modest efficacy means a lot, but the key secondary endpoint was the score expectations were shaken by Pfizer’s an- on the neuropsychiatric inventory (NPI). he presentation of full Phase II data nouncement that PF-05212377 was quietly The plan was to include 342 patients for Pfizer Inc.’s failed serotonin 5-HT6 terminated early in October 2015, after an but the protocol allowed for two interim T antagonist PF-05212377 at the Al- interim analysis of the drug as an add-on analyses. zheimer’s Association International Confer- therapy in a Phase II study of mild-to-mod- As it turned out, an interim analysis of ence is disappointing, but still leaves room erate Alzheimer’s disease indicated it was 185 treated patients showed no improve- for others in the class to succeed, like Lund- likely to fail. The termination was widely ment for any endpoints, which also in- beck Inc.’s idalopirdine and Axovant Scienc- publicized in February. Other drugs in the cluded the Cornell Scale for Depression in es Ltd.’s RVT-101, now dubbed intepirdine. same class that failed to see the light of CONTINUED ON PAGE 5

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

GSK’s specialty franchise head Vlad Hogenhuis on the big Is there still hope pharma’s big plans for 2018 2Q earnings results for 5-HT6 receptor have raised questions antagonist class in about Bayer’s long- Alzheimer’s? 5 12 term strategy 15

COVER / Pfizer’s Failed 5-HT6 Alzheimer’s Drug Leaves from the editor Hope For Class [email protected] 3 When Will Gilead Make Its M&A Move?

Quarterly results are an opportunity to take stock. 4 Semler Dirty Data: EMA Suspends Over 200 Products Lilly provides a case in point (p6). Applause and cheering met Lilly and Boehringer Ingelheim’s 6 Lilly Awaits New Rewards For Jardiance EMPA-REG cardiovascular outcomes data at the 7 Amgen Plugs Away On Repatha, With Hope For New European Association for the Study of Diabetes Monthly Product meeting last September. It was predicted that their SGLT-2 inhibitor Jardiance would overtake Johnson 8 R&D Bites & Johnson’s first-to-market Invokana. 9 Revlimid Trial Miss Removes Blockbuster Indication In contrast, the recent FDA advisory committee only For Celgene narrowly (by a vote of 12-11) endorsed a new indication of reduced CV mortality. Skeptical panelists argued 10 China Surprises With First CRISPR Trial Despite that changes to the study, which had first been de- Regulatory Lag signed to demonstrate CV safety but was later amend- 11 Japan Phase III Start Cements Roxadustat’s Lead ed to measure CV superiority, compromised its reliabil- ity. The partners are now pursuing further studies in 12 Ex-Naval Medical Officer Vlad Hogenhuis Describes heart failure-related hospitalization. The PDUFA date Life In Leadership At GSK for the CV death indication is in September, and addi- 14 Business Bulletin tional studies will take more time. Meanwhile, J&J’s CV study of Invokana is due to complete in February 2017. 15 Is Monsanto A Mistake When Pharma Is Bayer’s Last year EMPA-REG appeared to offer Jardiance a Leading Business? chance to piggyback over Invokana. But Invokana’s 16 Infographic a big piggy, booking H1 sales of $708m compared with Jardiance’s $157m, and Jardiance’s run-up may 18 Policy & Regulation Briefs not be sufficient to clear it. 19 Stockwatch: The Iceberg Beneath Gilead

20 Expert View: Biosimilar Confidence And Knowledge Needed In Europe, Say Experts exclusive online content 22 Pipeline Watch 23 Appointments Kidney Cancer Gets A Double Uplift From Latest CHMP Meeting Europe’s scientific committee, the CHMP, recommends approval for two anticancers, cabozantinib and lenvatinib, that will likely shake up the advanced kidney cancer sector. http://bit.ly/2ar3XHb

Public Biopharma Financings Plunge In 2016, But Is It A Sign Of Health? Public biopharmaceutical companies raised more than four times as much cash during the first half of 2015 than during the first half of 2016 – $20.9bn versus $4.7bn – reflecting macroeconomic and industry conditions that may not change in the second half of this year, but maybe that’s a good thing. @scripnews /scripintelligence http://bit.ly/2aYX2qA

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When Will Gilead Make Its M&A Move? JOSEPH HAAS [email protected]

While HCV sales continue to slow due to company reported product sales revenue programs internally and externally that we a lengthy list of factors, Gilead is seeing ($7.651bn) that was flat sequentially and can use to talk about why the long-term a strong launch for revised HIV combo down 6% year-over-year from $8.126bn in prospects for growth are as good as we therapies incorporating TAF – but most the second quarter of 2015. believe they are and that’s what we will be analysts believe that major M&A is need- “The outstanding question about Gil- focused on.” ed to offset stagnation. ead now is what it does next; with nearly $20bn in operating cash flow and close to STRONG GENVOYA LAUNCH ith ongoing stagnation in its $17bn in free cash flow, it has plenty of op- ENCOURAGES hepatitis C business, analysts are portunities,” Leerink Partners analyst Geof- It’s not just the TAF-related launches that are Wlooking for Gilead Sciences Inc. frey Porges wrote in a July 26 note. “So far, encouraging. Overall Gilead’s HIV sales rose to dip into business development activity its internal pipeline does not seem to have 10% year-over-year from second quarter as a way to return to growth, but the firm the scope, or probability of success, to ma- 2015, as well as 5% from the first quarter of offered few clues during its July 25 second terially improve its outlook or offset what 2016, bolstered by increasing use of Truvada quarter earnings call, other than that it is increasingly looks like a steadily eroding (emtricitabine/TDF) for prevention. The Fos- looking outside virology. mountain of HCV revenue.” ter City, Calif.-based firm also reported that HCV and HIV have made for a vigor- Beyond HCV and HIV, Gilead’s pipeline Genvoya is showing strong trends both for ous two-pillar antiviral business model at focuses on candidates for hepatitis B, non- switches from patients taking predecessor Gilead, but the still prosperous HCV fran- alcoholic steatohepatitis (NASH), cancer Stribild and from patients who had been on chise, anchored by sofosbuvir-containing and autoimmune disorders. CEO John non-Gilead HIV therapy. products, is showing unmistakable signs of Milligan indicated that its business devel- Gilead’s new chief operating officer slowdown. The company reported global opment focus likely would occur outside Kevin Young took a central role in report- HCV product sales of $4.0bn for the quar- of virology, to strengthen one of the bur- ing the company’s financials for the second ter, down 20% year-over-year from $4.9bn geoning areas other than hepatitis B. quarter, noting that non-HCV antiviral rev- in the second quarter of 2015, attributable “With regard to business development, enue was up 11% sequentially to $2.2bn, primarily to a sales decline for combo stal- obviously this is a company that has been thanks to the strength of the TAF-based wart Harvoni (sofosbuvir/ledipasvir), down very open about being interested in doing drugs. Genvoya “represents the most suc- more than 50% to $2.564bn on the quarter. more deals, especially deals of a certain cessful HIV launch since the introduction of A silver lining for the infectious disease size where we think we can get some le- Atripla, the first single-tablet regimen, a de- powerhouse is the strong launch being verage and we can use our organization cade ago,” he said. “After its first six months seen with revamped HIV drugs incorpo- to effectively accelerate or expand indica- of availability, Genvoya is already the most rating Viread follow-on tenofovir alafen- tions,” the exec said, citing last December’s prescribed regimen for both treatment- amide (TAF). in-licensing deal with Galapagos NV for au- naive and switch patients.” Gilead’s reformulated HIV quad pill Gen- toimmune candidate filgotinib and April’s To date, 78% of Genvoya prescrip- voya (elvitegravir/cobicistat/emtricitabine/ $400m buyout of Nimbus Apollo Inc. to tions have derived from patient switches, TAF), which updates Stribild with TAF in- strengthen its NASH pipeline. he added, with about half coming from stead of tenofovir disproxil fumarate (TDF), “We are very interested in continuing to Stribild and about 10% from non-Gilead gave Gilead reason for optimism with a add more things to our pipeline, especially therapies. At launch last November, Gilead strong launch including blockbuster run in the non-antiviral area where we contin- decided to rely on a safety edge to win pa- rate quarterly sales of $320m, slightly more ue to see growth in franchises,” he contin- tients over from Stribild, as it priced Gen- than double the combo’s $158m in world- ued. “It’s our hope as we exit this year [that] voya at parity with the older drug. wide sales during the first quarter. Two we’ll have a better, more complete story of While $268m of the Genvoya sales re- other TAF-containing HIV regimens also are corded during the second quarter were off to solid starts – Descovy (emtricitabine/ from the domestic market, the EU launch TAF) with $61m worldwide and Odefsey ‘We are very interested is proceeding as planned, Young said. Sales (emtricitabine/rilpivirine/TAF) with $58m in adding to our pipeline, were $30m in Europe during the quarter. in the US. The combo pill has gotten pricing approval especially in the non- in 11 EU markets so far, and already is the M&A LIKELY OUTSIDE OF market leader in Germany for both treat- VIROLOGY antiviral area where we ment-naïve and switch patients, after just Despite the promising present and fu- continue to see growth’ six months of availability. The drug is slated ture for Gilead in HIV, several analysts said to launch in the UK, France and Italy during Gilead’s return to growth likely hinges on the second half of 2016. M&A activity after a quarter in which the Published online 26 July 2016 scripintelligence.com 5 August 2016 | Scrip intelligence | 3 HEADLINE NEWS

Semler Dirty Data: EMA Suspends Over 200 Products Dirty data issues continue to plague Indian contract research organizations, denting the reputation of the beleaguered local industry and piling up challenges for marketing authorization holders.

ANJU GHANGURDE [email protected]

he European Medicines Agency the system due to which the firm was not SETBACK FOR INDIAN CROS (EMA) has now suspended close to able to identify “who and why this happened.” Action against Semler, industry experts say, T 300 products that relied on flawed The WHO had questioned the validity of comes as a setback for Indian CROs that bioequivalence studies done by the Ben- studies for a range of pre-qualified products have been keen to shrug off any impression galuru-based Semler Research, including: and those under assessment at the time that data integrity issues are a deep rooted erlotinib, saquinavir, celecoxib, eletriptan, including fixed dose combinations of efa- malaise. GVK Biosciences and Quest Life Sci- duloxetine, amoxicillin and eprosartan. virenz, lamivudine and tenofovir, azithromy- ences were earlier hauled up over data in- Marketing authorization holders for the sus- cin and isoniazid. tegrity issues. pended products include Sandoz NV, Teva The EMA said that the findings from FDA An industry expert told Scrip that a sec- Pharma Belgium NV, Mylan AB, Sanofi Aven- and WHO inspections call into question the tion of the Indian CRO industry (he estimates tis France, Zydus France, Ratiopharm GmbH quality management system in place at Sem- around 40-50 CROs) have significant bio- and Glenmark. ler, and thus on the reliability of the data of all equivalence-related activity driving business But the Agency’s action was not really bioequivalence studies, including those used and foreign companies could now get jittery entirely unexpected – both the FDA and to support marketing authorization applica- about having these studies done out of India. the World Health Organization (WHO) had tions in the EU. “Some could consider switching off earlier pulled up Semler over compliance “The EMA’s Committee for Medicinal Prod- from India; even Indian firms that use local deviations. ucts for Human Use (CHMP) has concluded CROs for bioequivalence studies for exports The EMA said its review followed an FDA that the studies conducted at Semler cannot could be cautious, though cost economics inspection that raised several issues at Sem- be accepted in marketing authorization ap- are a factor,” he said. Bioequivalence studies ler Research Centre Private Ltd’s bioanalytical plications in the EU. Thus, no medicines can typically form the basis for approval of ge- site, including the “substitution and manipu- be approved on the basis of these studies,” neric medicines. lation of subjects’ clinical samples”. The FDA the EMA statement said. Dilip Shah, secretary general of the Indian had earlier said that Semler engaged in prac- Pharmaceutical Alliance (IPA), which repre- tices and processes that undermined the sents leading domestic drug firms, however, analytical methods used at the firm which ‘It would be short maintained that while the “local unknown resulted in the submission of “invalid” study sighted to tarnish CROs” may suffer, the established global ones data to the agency. with “good internal oversight” may even ben- Semler was also previously pulled up by the image of the efit following the EMA action. “India still con- the WHO for “critical and major” deviations tinues to be cost effective, providing access from good laboratory practice (GLP) and Indian CRO industry to a large patient pool and trained doctors,” good clinical practice (GCP), resulting in a Shah told Scrip. stinging notice of concern (NOC) against the based on few, Industry bodies were quick to swing into Indian CRO in April. isolated incidents,’ damage control mode. The Indian Society The NOC referred to an “indicator of fraud” for Clinical Research (ISCR), whose mem- and manipulation of at least five studies over – ISCR bers include several large multinational an extended period of time suggesting that firms and clinical research organizations, this is a “common practice”. The WHO at the told Scrip that it would be “short sighted time said it believed that to execute such ma- The Agency has also recommended that and damaging” to the reputation of many nipulation, several staff members on various medicines currently being evaluated for au- high quality Indian CROs to tarnish the im- levels of the organization had to be “collabo- thorization and which rely only on bioequiv- age of the Indian CRO industry based on a rating and co-ordinating”. alence studies from this site should not be “few, isolated” incidents. “The issue is thus not confined to a single authorized until bioequivalence is demon- “The quality of clinical research work done person operating outside of the quality man- strated using alternative data. in India is comparable to that of any other agement system,” the WHO had said. There is, however, currently no evidence country,” ISCR president Suneela Thatte told Semler had, the NOC said, acknowledged of “unexpected harm or lack of effectiveness” Scrip. ISCR noted that there have been over that four FDA studies and one WHO study with any medicine approved on the basis of 40 US FDA clinical trial inspections in India had “questionable” data and these trends studies conducted at Semler, the EMA state- with no critical findings reported; there have were not “physiologically explainable” and ment noted. also been several all clear European regula- that there were system gaps identified dur- Semler could not immediately be reached tory audits of Indian clinical trial sites. ing the retrospective investigative audit in for a comment. Published online 25 July 2016

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CONTINUED FROM COVER analysis) and that the class needs longer to with Aricept is similar to Aricept mono- Dementia (CSDD) the Mini-Mental State show an effect, he said. The study was also therapy, Datamonitor analysts noted in Examination (MMSE), the ADAS Activities relatively small and short, he added. a March 2016 report on the Alzheimer’s of Daily Living (ADS-ADL) and Columbia It’s also unclear how strong the diagno- disease pipeline. Suicide Severity Rating (CSSR). sis of Alzheimer’s disease was in the 185 “This superb tolerability is an important In fact, performance in the test drug patients treated – development of better differentiator for RVT-101, with common arm was numerically worse for the primary diagnostics has been a challenge for the side effects including nasopharyngitis and endpoint and all secondary endpoints field, Hendrix said. urinary tract infection, and the low inci- aside from CSDD, investigators reported. Pfizer’s drug showed adverse events sim- ilar to the comparator arm.

BUT HOPE FOR OTHERS IN THE CLASS The efficacy results are “discouraging, but do not necessarily impact the outlook of 5-HT6 receptor antagonist class of drugs,” as there are a number of aspects of the trial design that could explain the failure and which differ from the way idalopirdine and RVT- 101 have been tested, Datamonitor analyst Maha Elsayed commented in a dispatch from the meeting. Both drugs showed efficacy in Phase II and Phase III design mostly mirrors mid- stage protocols. Lightspring Shutterstock: The 12-week duration of treatment used in the Pfizer trial may not have been long The Alzheimer’s Association is still en- dence of additional AEs should encourage enough to show a cognitive benefit, she couraged that candidates from Lundbeck physicians to use it as an adjunctive treat- said. In studies of idalopirdine and RVT-101, and Axovant progressed to Phase III, which ment,” the report states. benefit was seen after 24 weeks. offers hope for a new option in treating In addition to the Pfizer data, the AAIC Elsayed also noted that differences in pa- cognitive symptoms in patients with Al- meeting featured a poster presentation tient population may have played a role, as zheimer’s, as millions of Americans are liv- of Suven’s SUVN-502 in an initial proof- patients with neuropsychiatric symptoms ing with the disease, he said. of-concept study that tested the drug as are more difficult to treat. Lundbeck announced July 7 that an add-on to Aricept and Allergan PLC’s There are also some differences between idalopirdine was granted Fast Track desig- Namenda (memantine) and suggested drugs in the class in terms of the mecha- nation from FDA. The company is running cognitive benefits after treatment for 14 nism of action, she noted. “For example, four Phase III studies in 2,500 patients and days. The findings are in line with reported in addition to its 5HT-6 activity RVT-101 is expects data in the second half of this year. cognitive and mechanistic effects of other also an antagonist of the 5HT-2A receptor,” Axovant’s pivotal data will be completed 5-HT6 receptors antagonists, Elsayed not- whereas there is no binding at the 5HT-2A in October 2017. The company has a spe- ed, though obviously early. receptor for PF-05212377,” Elsayed said. cial protocol agreement with FDA for one The Datamonitor report also comments James Hendrix, director of Global Sci- Phase III study in 1,150 patients of the drug that “it is becoming widely accepted that ence Initiatives in the Alzheimer’s Asso- as an add-on to Aricept. antagonism of 5-HT6 receptors invokes an ciation’s medical and scientific relations Axovant’s RVT-101 has looked inferior improvement in cognition in a range of division, agrees that the outlook still looks as a monotherapy compared to Aricept in learning and memory models, and that this good for other drugs in the class, such as Phase II. It did show efficacy in mid-stage effect is mediated through enhancements idalopirdine and intepirdine. trials when added to cholineresterase in- of cholinergic, glutamatergic, norepineph- It’s common in drug development to hibitors in terms of ADAS-Cog and ADCS- rinergic, and dopaminergic neurotransmis- see different outcomes for drugs with the ADL endpoints, but had no effect on the sion, together with learning-associated same mechanism of action; sometimes a clinical dementia rating scale CDR-SB. neuronal remodeling.” candidate isn’t good enough for whatever During an investor call at the 2015 Improvements have been modest, but reason, Hendrix, a former top exec in cen- AAIC meeting, Axovant execs said that there is “precedent for drugs from new tral nervous system diseases at Sanofi, com- CDR-SB is an endpoint more appropriate classes to have commercial success, even mented in an interview. In the case of PF- for earlier-stage disease and this is not without standout efficacy,” the analysts 05212377, it could be because the study a primary endpoint in Phase III. Further- concluded. was stopped too early (after an interim more, the safety profile for intepirdine Published online 25 July 2016 scripintelligence.com 5 August 2016 | Scrip intelligence | 5 HEADLINE NEWS

Lilly Awaits New Rewards For Jardiance EMILY HAYES [email protected]

Although Jardiance is supported by out- said that the company is optimistic it will agonist Trulicity (dulaglutide), approved in comes data, it has not yet been incorpo- get an indication for cardiovascular benefit, September 2014 by FDA, were notewor- rated into labeling, nor has it translated as opposed to merely the inclusion of data thy at $201.3m. into greater sales. in labeling. Rice said that the product is capturing The company expects that after FDA 25% of new patient starts in a GLP-1 class li Lilly & Co. has reported a cardiovas- makes its decision, there could be a – and in many markets outside of the US cular outcomes benefit for its SGLT-2 change in treatment guidelines some- the company is seeing uptake comparable Etargeted diabetes drug Jardiance, but time next year to reflect the EMPA- to Novo Nordisk AS’s GLP-1 agonist Victoza still awaits the translation of that clinical ad- REG data, Conterno said. Lilly reported (liraglutide). vantage into sales. $40.1m in sales for Jardiance in the quar- “In addition to our strong performance, ter, compared with $383m for J&J’s com- we’re benefiting from strong growth of the peting Invokana. GLP-1 class, with the US market growing Despite the outcomes data supporting 30%,” Rice said. Jardiance in the EMPA-REG study, “J&J has Kliff noted that “Lilly has the potential to done an excellent job of locking up prime own this category,” given that it does not formulary position,” Diabetic Investor pub- appear that GlaxoSmithKline PLC is putting lisher David Kliff said in a July 26 note. much effort into its once-weekly GLP-1 He expects the entire SGLT-2 class will agonist Tanzeum (albiglutide), and Astra- continue to grow “and Jardiance will get its Zeneca PLC made a lot of mistakes with its fair share of this growth. Will it replace In- once-weekly GLP-1 Bydureon (long-acting vokana as the leader in the class? Unlikely, exenatide). but we suspect Jardiance will close the Looking ahead, Lilly said that it is plan- gap,” Kliff wrote. ning 20 new drug launches between 2014 Sales growth for the class is now in the and 2023. One of the next filings will be for 25% range Jardiance’s share with new pa- the firm’s CDK4/CDK6 inhibitor abemaci- tients with endocrinologist prescribers is clib, which will compete with Pfizer Inc.’s over 35%, according to IMS Health data, Ibrance (palbociclib).

Shutterstock: Sergey Nivens Sergey Shutterstock: and outside the US the company has seen The company presented Phase II results very strong uptake in Italy and encourag- from the MONARCH 1 study at the Ameri- Jardiance (empagliflozin), which is part- ing trends across all countries, Chief Finan- can Society of Clinical Oncology annual nered with Boehringer Ingelheim GMBH, cial Officer Derica Rice said. meeting in June. There will be an interim demonstrated an improvement in the EM- The company guided for total annual readout of MONARCH 2, a Phase III study, in PA-REG outcomes study and the company sales of $20.6bn to $21.1bn, in line with “the near future,” CEO John Leichleiter told has been looking to get revised labeling consensus, but Jardiance quarterly sales the call. with a new indication for reduction in risk were lower than consensus expectations “Given the close proximity of this read- of cardiovascular mortality. of $63m, Jefferies analyst Jeffrey Holford out to the final MONARCH 1 data, we ex- An FDA advisory committee recently observed in a July 26 note. pect to submit MONARCH 1 data to the voted in favor of a claim for Jardiance, but Based on the volume of scripts, analysts FDA as early as later this quarter after the FDA has not acted on the advice yet. For expected higher sales, but Conterno ex- interim MONARCH 2 read,” Leichleiter said. now, Johnson & Johnson’s SGLT-2 inhibitor plained that there has been much higher Abemaciclib has breakthrough therapy Invokana (canagliflozin) has the edge as utilization of copay cards for Jardiance. designation with FDA. the first in the class approved. The company has a “robust plan” with The company is also developing the In its second quarter earnings call July 26, partner Boehringer to promote Jardiance, anti-amyloid beta antibody solanezumab Lilly reported sales of $5.4bn, up 9% from the exec asserted. in Alzheimer’s disease. Lilly is planning a the same time last year. Of that, the insulin “Clearly we view this as a very significant top-line release from a study of early stage product Humalog was the top seller, with opportunity, so we’re going to be fully re- (prodromal) Alzheimer’s disease by the end $702m in revenue, followed by the cancer sourced,” Conterno said. of this year. drug Alimta (pemetrexed) in number two That means making all of the proper But even if things don’t pan out with position, with $607m in sales. investments when it comes to “ensuring solanezumab, the company expects a Development in the company’s diabetes that we have the right reach” for both pri- minimum growth of 5% annually between franchise was, as expected, an important mary care specialists (cardiologists and now and the end of the decade, according part of the company’s earnings call. En- endocrinologists), the exec added. Quar- to Rice. rique Conterno, president of Lilly diabetes, terly sales of Lilly’s once-weekly GLP-1 Published online 26 July 2016

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Amgen Plugs Away On Repatha, With Hope For New Monthly Product In a very strong second-quarter earnings report, Amgen reports just $27m in worldwide sales for cholesterol-busting PCSK9 inhibitor Repatha, as reimbursement continues to present a big hurdle. EMILY HAYES [email protected]

mgen Inc. is plugging away with the cholesterol drug Re- week. On July 11, Amgen announced FDA approval of a 420mg patha (evolocumab), which had just $27m in worldwide dose given once monthly in a hands free Pushtronex system, Asales in the second quarter, amid continued reimbursement through an on-body infuser that administers the drug subcuta- challenges, and has hopes that launching a monthly version of the neously. “There appear to be a fair amount of patients who pre- drug will give it an edge. fer to have a convenient once-a-month dose. We’ll be coming to Amgen’s Repatha and Sanofi/Regeneron Pharmaceuticals market in the next couple of weeks,” Hooper said. Inc.’s competing PCSK9 inhibitor Praluent (alirocumab) were ap- Out of the $27m in total sales for Repatha, $7m derived from outside proved in the summer of 2015, after much fanfare and inves- the US. The company said that it continues to make good progress tor excitement over the class’s dramatic LDL-lowering. Sponsors with Repatha’s reimbursement negotiations on a country-by-country had sought very broad labeling, but without outcomes data in hand, the initial approvals were limited to high-risk patient basis and is in the early launch stages in several European countries. populations. 2Q 2016: Drug Sales Highlights* Both drugs have struggled to gain a foothold without the out- Enbrel (etanercept): $1.5bn (+10%) comes data and because with price tags around $14,000, payers have imposed barriers to use, such as cumbersome utilization Neulasta (pegfilgrastim): $1.1bn (-1%) Prolia (denosumab): $441m (+30% management requirements, which cardiologists say make it very difficult to treat even very high-risk patients. Xgeva (denosumab): $381m (15%) Still, Repatha is showing signs of progress: during its July 27 Kyprolis (carfilzomib): $172m (+45%) earnings call, Amgen reported second-quarter sales of $27m Neupogen (filgrastim): $141m (-23%) worldwide, up from $16m in the first quarter. Sanofi is set to re- Blincyto (blinatumomab): $30m (+76%) port its earnings on July 29; the company has been open about Repatha (evolocumab): $27m (% change NA) reimbursement challenges in the past. Amgen’s report on Repatha was in line with analyst expecta- *Sales growth compared to same period in 2015 tions for that product, in a quarter with better-than expected PIPELINE UPDATES performance overall. In addition to working on Repatha, the company is gearing up for new Amgen reported total quarterly revenue of $5.7bn, up by 6% from the same period in 2015. Product sales were up by 5%, driv- indications, new launches and advancement of its late-stage pipeline. en by core products like the top-selling inflammatory disease It awaits results from the Phase III CLARION study of the prote- drug Enbrel (etanercept), which rose to about $1.5bn, thanks to asome inhibitor Kyprolis (carfilzomib) in newly diagnosed, trans- price increases and despite lower volume. plant-ineligible, relapsed/refractory multiple myeloma, which Addressing Repatha performance during the call, Anthony are due in the second half of this year. The trial tests the drug Hooper, executive VP of global commercial operations, said that head to head against Takeda Pharmaceutical Co. Ltd.’s Velcade the company’s cardiovascular teams have executed well in the (bortezomib), both on top of standard of care therapies. marketplace, but that utilization management criteria and pro- On July 22, Amgen and partner UCB Group announced the fil- cesses by insurers and pharmacy benefit managers continue to ing of romosuzumab for post-menopausal osteoporosis in the US. be the “biggest hurdle.” Results from the Phase III pivotal study are slated for presentation “We are working diligently to address these restrictions so at the American Society for Bone and Mineral Research annual the appropriate patients are able to access the treatment” pre- meeting in September. Amgen also plans to present Phase IIb scribed for them, Hooper said. data for its migraine drug erenumab (AMG 334), a CGRP inhibi- Amgen expects data from a coronary imaging study later this tor, at the European Headache and Migraine Trust International year and from the large, event-driven FOURIER outcomes study in Congress in September. the first quarter of 2017. “This is a large study at 27,500 patients and we remain focused on generating the most robust data set Amgen’s sales guidance for this year has increased from a possible in this field from an analysis of the completed study,” Sean range of $22.2bn to 22.6bn up to range of $22.5bn to $22.8bn. Harper, executive VP of research and development, told the call. The company’s operating margin of 51.4% continues to improve The company also said it is also excited to offer a monthly dos- and is already very close to AMGN’s 2018 guidance of 52%-54%, ing option, which is not available for Praluent. The initial dose of Evercore ISI Group analyst Mark Schoenebaum observed in a Repatha approved was 75mg, given subcutaneously every other July 27 note. Published online 27 July 2016 scripintelligence.com 5 August 2016 | Scrip intelligence | 7 R&D BITES

Tobira, Dong-A Stick To NASH Plans Despite No Fanfare For US Approval Of Sanofi’s CENTAUR Results GLP-1 Adlyxin The failure of Tobira’s cenicriviroc to Sanofi has secured US approval for its a once-daily mealtime GLP-1 injec- meet its primary endpoint in the Phase tion Adlyxin (lixisenatide) as an adjunct to diet and exercise for the treat- IIb CENTAUR study has raised some ment of adults with type 2 diabetes, but as the sixth GLP-1 product to concerns in South Korea over the pros- enter this market the drug is unlikely to gain a strong foothold. Adlyxin, pects for a combo therapy with Dong-A which is marketed as Lyxumia in more than 40 countries, is more than a ST’s evogliptin. But the two firms are day late and a dollar short as it finally gets the thumbs up from the US sticking to their clinical development FDA for the treatment of adults with type 2 diabetes, and as such poses plans based on the positive secondary little threat to market-leading GLP-1 products Novo Nordisk AS’ Victoza endpoint outcome in the study. Tobira (liraglutide) and Eli Lilly & Co.’s Trulicity (dulaglutide).While access to announced on July 25 that cenicriviroc the US market is always crucial due to the size of the market, Datamoni- missed its primary endpoint of improve- tor Healthcare analyst Rajan Sharma told Scrip that Adlyxin’s outlook as ment in non-alcoholic fatty liver disease a standalone product isn’t particularly positive. “Lixisenatide is the sixth (NAFLD) activity in the CENTAUR trial. GLP-1 agonist to launch in the US and it has shown no real advantages However, the Phase IIb study did demon- over market leading drugs in this class,” Sharma said. He added that while strate a clinically and statistically signifi- Adlyxin is likely to compete with the smaller brands within the class such cant improvement in fibrosis of at least as GlaxoSmithKline PLC’s Tanzeumand, AstraZeneca PLC’s Byetta and one stage without worsening of non-al- Bydureon; Sanofi’s offering won’t contend with the two big players. coholic steatohepatitis (NASH) after one [email protected], 29 July 2016 year of treatment, a key secondary end- point. South Korean brokerage HI In- vestment & Securities said that the latest been pursuing a heavy stock-promoting for its Alzheimer’s disease therapy LMTX, study outcome had “raised uncertain- campaign since November 2015, cre- having identified positive results in a ties” over the successful clinical develop- ating a hype around its potential Alz- subgroup analysis of a pivotal trial that ment of the combination therapy, and heimer’s therapy, but mixed Phase IIa failed overall, but the analysis has limita- cut its valuation of Dong-A’s evogliptin results in a small number of patients tions and there are questions that could pipeline by 70%. In April, Dong-A, a lead- caused investors to back off last week, affect the entire field of tau-based inter- ing South Korean pharma firm, licensed with the New York-based biotech drop- ventions in Alzheimer’s disease. TauRx out evogliptin’s development and sales ping from a steady price of $7.3 at the Therapeutics presented the results of the rights in the US, Europe, Canada and start of the week to a close of just $3.5 first Phase III study evaluating LMTX’s Australia to US-based Tobira in a deal per share on July 28 (NASDAQ). The (leuco-methylthioninium) efficacy and worth $61.5m in upfront and milestone sharp decline prompted Anavex to put payments, plus sales royalties. safety in Alzheimer’s disease at the Alz- out another press release on July 29, fol- [email protected], 28 July 2016 heimer’s Association International Con- lowing from its initial data release on ference in Toronto on July 27. The study July 27, confirming the “positive” data failed to demonstrate LMTX’s therapeu- Anavex Stock Price Crash: A for ANAVEX 2-73. The second press re- tic benefits in patients with mild to mod- lease highlights that the Phase IIa study erate disease. However, when a subgroup Fault By Trial Design? was a first in Alzheimer’s patients trial analysis was carried out in patients re- focused on testing safety of ANAVEX Anavex Life Sciences’ unabashed self- ceiving LMTX as a monotherapy, an 2-73. It remains to be seen if this update promotion since late-2015 for its lead- efficacy signal emerged. While TauRx from the company will be enough to ing pipeline product ANAVEX 2-73, Therapeutics, a Singapore-based neuro- convince skittish investors though. which is being studied as a treatment degenerative drug and diagnostics firm [email protected], 29 July 2016 for Alzheimer’s disease, may have been spun out of the University of Aberdeen, one reason the firm’s stock crashed attempted to spin these findings as posi- down last week following the presenta- tive and encouraging, the analysis was tion of Phase IIa data at the Alzheimer’s TauRx’s Data Massage misleading. TauRx Therapeutics plans Association International Conference. Can’t Work Out Kinks Of to discuss these findings with regula- But the study with no control arm and tory authorities after the readout of the only 32 patients for a neurological dis- Failed LMTX Study second pivotal Phase III trial evaluating order also has some analysts question- TauRx Pharmaceuticals Ltd. is going to LMTX in mild AD patients. ing how robust the data are. Anavex had talk to regulators about a route forward [email protected], 28 July 2016

8 | Scrip intelligence | 5 August 2016 © Informa UK Ltd 2016 HEADLINE NEWS

Revlimid Trial Miss Removes Blockbuster Indication For Celgene Celgene Corp.’s hopes of extending the market reach of its blockbuster oncology therapy Revlimid (lenalidomide) have taken a blow as Phase III data for the drug in elderly diffuse large B-cell lymphoma (DLBCL) patients have failed to show benefit on overall survival.

LUCIE ELLIS [email protected]

The highly anticipated REMARC trial – which evaluated main- buster Revlimid by expanding into additional lymphoma indica- tenance therapy with Revlimid compared with placebo in elderly tions,” because DLCBL is the most common type of NHL subgroup. DLBCL patients responding to first-line rituximab plus CHOP che- However, Biomedtracker has now highlighted the Phase III RELE- motherapy (R-CHOP) induction therapy – achieved its primary end- VANCE study as the most interesting in Celgene’s ongoing Revlimid point of a significant improvement in progression-free survival, but program due to its potential market size. Results from RELEVANCE an interim analysis of overall survival data produced disappointing are expected in the first half of 2017. results for Celgene Corp. and its partner the Lymphoma Academic Datamonitor Healthcare analyst Rachel Lloyd agreed the poor Research Organisation (LYSARC). Phase III data is a “major blow” for Celgene. “Revlimid is one of Cel- gene’s biggest drugs and it had the potential to become a block- buster in this indication due to the size of the market and lack of targeted therapies that currently have approval,” Lloyd told Scrip. However, she highlighted that the trial failure is not a big surprise as a number of drugs have failed to show efficacy in this maintenance setting, including Roche’s Rituxan (rituximab), which has revolu- tionized the treatment of DLBCL since it was granted approval for this indication. Earlier in July Novartis also saw disappointment in this area of development that resulted in it suspending a Phase III trial of m- TOR inhibitor Afinitor (everolimus) after it failed to demonstrate a significant increase in disease free survival in patients in complete remission after treatment with Rituxan containing chemotherapy. Novartis is continuing to explore options for Afinitor in DLBCL but Biomedtracker has cut the drug’s likelihood of approval rating in

Shutterstock: jannoon028 Shutterstock: this indication to 30% (5% below the average for a similar product at the same stage of development). Lifecycle management of its leading oncology drug is a current priority for Celgene but as a result of Revlimid’s failure to show a positive effect on overall survival, the big biotech will not to pur- Trial failure is not big surprise as sue approval for its cancer therapy in this DLBCL population. This is unfortunate for Celgene as the maintenance setting in DLBCL has other drugs have failed to show huge commercial potential due to the combination of increasing disease incidence and improved patient survival due to successful efficacy in this maintenance setting treatment with rituximab containing chemotherapy. However, the company confirmed it will continue to progress Revlimid is still in development for a subtype DLBCL population four other ongoing non-Hodgkin’s lymphoma Phase III trials for in the ROBUST trial but even if it does manage to gain approval Revlimid, including one in another DLBLC patient population. in this setting the commercial rewards will be nowhere as great They are: as if the drug was approved as a maintenance therapy, Lloyd said. • RELEVANCE, a combination with rituximab in previously untreat- Topline data from the ROBUST study are not expected until 2018. ed follicular lymphoma; Revlimid, which boasted worldwide sales of $5.8bn for Celgene • AUGMENT, a combination with rituximab in relapsed/refractory in 2015, is already indicated for the treatment of myelodysplastic follicular and marginal zone lymphoma; syndrome (MDS), multiple myeloma and mantle cell lymphoma – • MAGNIFY, a combination with rituximab in relapsed/refractory with the latter being the most recent approval in June 2013. How- follicular, marginal zone and mantle cell lymphoma; and, ever, it has previously been suspended in a number of oncological • ROBUST, a combination with R-CHOP in previously untreated ac- indications, including NHL disease cutaneous T-cell lymphoma; tivated B-cell (ABC) type DLBCL. prostate cancer; colorectal cancer; melanoma; ovarian cancer; my- Analysts at Biomedtracker said the mixed results from the RE- elofibrosis; and renal cell cancer. MARC study have “hurt Celgene’s plans to grow sales of its block- Published online 26 July 2016 scripintelligence.com 5 August 2016 | Scrip intelligence | 9 HEADLINE NEWS

China Surprises With First CRISPR Trial Despite Regulatory Lag BRIAN YANG [email protected]

The lack of a comprehensive regulatory “proceed cautiously” in dose escalation. would not seem to bode well for local sci- pathway has not hindered Chinese re- Biomarkers will also be collected to analyze entists looking to forge ahead - the national searchers from forging ahead with the patients’ response. government is not expected to sit idle and world’s first human clinical study using Locally based biotech Chengdu Med- allow others to take the lead in this ground- CRISPR-Cas9 gene editing technology, genCell will also collaborate with the hos- breaking area. which will be used to treat advanced pital to provide support for cell selection to It seems that it will allow selected major lung cancer. ensure correct gene knock-out before the hospitals to start experimental trials after edited T-cells are infused back to patients. obtaining clearance from their ethics com- ncologists at Huaxi Hospital in Chi- mittees. In a document released March na’s eastern Sichuan province are AHEAD OF US 2015, the National Health and Family Plan- Opreparing to start what appears to The development is set to put China ning Commission laid out seven major con- be the world’s first human clinical trial using ahead in the world and before the US in ditions for medical facilities to be able to the gene editing technology CRISPR-Cas9, terms of the practical clinical application start clinical work with cell-based therapies. to treat patients with advanced non-small of the cutting edge CRISPR (Clustered Among these were a requirement for hos- cell lung cancer. Regularly Interspaced Short Palindromic pitals to have Class 3A status, meaning they Led by Lu You, the head of the hospi- Repeats) technology. are certified to conduct clinical trials and tal’s lung cancer division, the study has In June, scientists from the University of have a certain level of medical, teaching and obtained ethics committee clearance and Pennsylvania won a crucial approval from research capabilities. Clinical sites should also will start in August in 15 patients with met- the Recombinant DNA Advisory Commit- have a “comprehensive and thorough” stem astatic NSCLC who have failed previous tee, a federal ethics board at the US Nation- cell quality control system; primary investiga- chemotherapy, radiology and other treat- al Institutes of Health, to use CRISPR-Cas9- tors with a senior medical professional certifi- ments, according to a report in Nature. modified cells against multiple myeloma, cate and trained in GCP; an ethics board ca- Lu, the study’s primary investigator, had not melanoma and sarcoma. This study is being pable of reviewing stem cells-related issues; responded to a Scrip request for comments sponsored by Silicon Valley billionaire Sean and the ability to handle adverse events. by the time of publication, but a person an- Parker through the Parker Institute for Can- After the issuance of a document allow- swering a call at the hospital confirmed that cer Immunotherapy. ing the studies, the cell therapies will not the study will start next month and that pa- However, the UPenn trial has still to ob- be classified as Category 3 medical prod- tient screening is ongoing. Qualified patients tain final approval from the US Food and ucts, meaning they won’t be subject to include these who have failed to respond to Drug Administration, and the university regulation by the China FDA, the commis- third-line treatments, she noted. has said it expects to commence the trial sion implied. While the facilities can’t apply A description of the planned Phase I, in the three indications by the end of the trial results outside the study design, they dose escalation trial on clinicaltrials.gov year. Others planning clinical trials include can use the data towards applying for sub- shows that Lu and his team will collect pe- Editas Medicine Inc., CRISPR Therapeutics sequent clinical trials with regulatory agen- ripheral blood lymphocytes and then use and Intellia Therapeutics Inc. cies, the NHFPC said. the CRISPR-associated endonuclease Cas9 In China, lung cancer is a priority disease The NHFPC’s guidelines define CRISPR as in the lab to knock out the gene coding for target given that it is the most prevalent type a cell technology conducted by research programmed cell death protein 1 (PD-1). of malignancy among Chinese males and the hospitals/institutions for research purposes, T-cells from patients’ own blood will be most deadly cancer in the country overall. which is why for now the technology falls under its remit, given that the commission selected and expanded ex vivo, and then Merck & Co. Inc. and Bristol-Myers Squibb is the regulatory agency for hospitals. The the engineered cells with the knocked out Co. are developing their PD-1 checkpoint China FDA usually regulates actual products, gene infused back into participants. Given inhibitors Keytruda (pembrolizumab) and and treatment methodologies are therefore PD-1’s well characterized role as an immune Opdivo (nivolumab) in Phase III trials for more of a grey regulatory area at present. checkpoint, the researchers hope the modi- various indications in China, where a flur- From the editors of PharmAsia News. fied cells will improve progression-free and ry of domestic biotechs are also vying to Published online 25 July 2016 overall survival, with a planned completion launch the nation’s first PD-1 antibody. date for the trial of April 2018. Due to potential immune overreaction REGULATORY FRAMEWORK CLICK with the engineered T-cells, Huaxi hospi- Although China has not issued a full official Read full story at: tal researchers say the primary endpoint regulatory pathway for novel cell therapies http://bit.ly/2aLM34v is safety and tolerability, and that they will using technologies such as CRISPR - which

10 | Scrip intelligence | 5 August 2016 © Informa UK Ltd 2016 HEADLINE NEWS

Japan Phase III Start Cements Roxadustat’s Lead Astellas/FibroGen’s oral candidate for anemia in chronic kidney disease has moved into Phase III in Japan on the basis of promising Phase II results, cementing the global development lead for the first-in-class product and taking it closer to a potentially big market. IAN HAYDOCK [email protected]

stellas Pharma Inc. has begun dosing in a Phase III program ranged from 10.20-10.53g/dL with increases varying between in Japan with roxadustat, it and partner FibroGen Inc.’s oral 1.33 and 1.57g/dL), versus 1.25g/dL and 1.42g/dL respectively Asmall molecule inhibitor of hypoxia-inducible factor prolyl for placebo. Roxadustat was well tolerated in both studies hydroxylase (HIF-PH), for the treatment of anemia in patients with and one death in the second study was deemed unrelated to chronic kidney disease (CKD). the drug. The trial start triggers a $10m milestone payment to FibroGen The companies have now completed a suite of six Phase II stud- under the two firms’ 2006 agreement for the drug, through which ies in either setting, and the Japanese results were consistent with the Japanese firm holds development and commercialization those elsewhere, they said. rights to roxadustat (along with selected sister compounds) in Eu- The ongoing global Phase III program includes eight studies to rope, the CIS, Middle East and South Africa, along with Japan (for support approval filings in the US and Europe - a US submission which rights were granted in 2004). is expected in 2018 - and two in China, where AstraZeneca PLC, The 2006 alliance was worth $300m upfront and up to $465m in FibroGen’s partner for non-Astellas regions including the US, could development milestones, with Astellas also taking an undisclosed make a submission this year. equity stake in San Francisco-based FibroGen. Roxadustat (FG-4592/ASP1517) is FibroGen’s most advanced LOOK BEHIND YOU product candidate and stands to become a first-in-class oral thera- HIF is a protein transcription factor that triggers the physiological py for CKD-related anemia if approved. With a standard three times response to low oxygen, turning on gene transcription to make a week dosing regimen, it offers important convenience ben- erythropoietin and thereby stimulate red blood cell production. efits overcurrent erythropoiesis-stimulating agent (ESA) therapies, The hope that is that the new class of HIF-PH inhibitors will trig- which are given intravenously. ger a more “natural” mechanism for raising red blood cell levels Roxadustat is already in an ongoing global, 10-study Phase III compared to ESAs, and also avoid the cardiovascular side effects development plan for use in CKD sufferers either receiving or not that can be caused by large doses of these agents. receiving dialysis (the latter accounting for the majority of patients), But although FibroGen has the lead in the HIF-PH field, others with the sites in Japan now added to this program. are coming up behind including Akebia Therapeutics Inc., whose Under the 2006 agreement with FibroGen, Astellas is covering vadadustat is also in Phase III and partnered with Mitsubishi Tanabe the costs of development in Japan while the two companies share Pharma Corp. for Japan and Asia. these equally in the other territories. There are a further eight or so HIF-PH inhibitors in clinical devel- The two companies also unveiled new results from two Phase II opment including GlaxoSmithKline PLC’s daprodustat moving into trials in Japan conducted in either patients receiving or not receiv- Phase III, a competitive situation that recently prompted another ing dialysis, with both showing increases in hemoglobin (Hb) levels player, Bayer AG, to search for licensees for its candidate molidustat over six weeks of treatment. rather than pursue Phase III trials itself. Helped by its probably first to market position, Datamonitor HB INCREASES Healthcare sees global roxadustat sales rising to $2bn by 2024, The study in 107 patients not on dialysis assessed roxadustat 50mg, based on its convenient dosing without need for medical supervi- 70mg or 100mg three times a week for the first six weeks and then sion, safety, and lack of requirement for concomitant intravenous dose-titrated every four weeks until Hb response, thereafter main- iron administration. tained with weekly or three times a week dosing. These should confer a “huge advantage” over current treatments Mean Hb increases ranged dose-dependently from 0.200- in a worldwide anemia in CKD market worth around $5.2bn in 0.570g/dL per week in the first six weeks, compared with a de- 2015, Datamonitor Healthcare analysts said. Astellas and FibroGen crease of 0.052g/dL for placebo. Around 94% of roxadustat patients put the global CKD patient population at around 200 million, in- achieved Hb correction, versus roughly 15% achieving a response cluding 30 million adults in the US. on placebo. Although cheaper biosimilar epoetin and erythropoietin prod- The 130-patient trial in subjects receiving dialysis enrolled ucts will start becoming available over the next few years, Data- participants who had discontinued previous ESA therapy and monitor Healthcare sees roxadustat as having the potential to had Hb levels of more than 9.5g/dL, who were given the three replace these as the standard of care. The total Japanese anemia fixed doses of roxadustat three times a week or intravenous in CKD market is forecast to expand to $882m by 2024, with roxa- once-weekly darbepoietin for the first six weeks, with doses ti- dustat sales reaching $515m the same year. trated to the desired Hb level every four weeks. During weeks From the editors of PharmAsia News. 18-24, average Hb levels achieved (a secondary endpoint) Published online 27 July 2016 scripintelligence.com 5 August 2016 | Scrip intelligence | 11 HEADLINE NEWS

Ex-Naval Medical Officer Vlad Hogenhuis Describes Life In Leadership At GSK LUCIE ELLIS [email protected]

Dr. Vlad Hogenhuis, a Merck & Co. Inc. person helps you. I keep this mentality at gelos, who was very interested in hiring phy- veteran who joined GlaxoSmithKline PLC work, whether it is projects at GSK or external sicians to work at Merck. He had built a very in 2012, is currently responsible for the projects, it’s all about the relationships that successful company focused on R&D for new UK company’s vast specialty franchise – bring a team together. medicines with a very rigorous approach, formulating a global strategy for novel but he was also convinced it was important drug development and product launches LE: What was the first job that saw you enter to have healthcare professionals at the com- in the areas of cardiovascular, neurosci- the healthcare industry? pany to ensure that the value of the medical ence, immunology, oncology, infectious VH: Just after graduating medical school I intervention was seen in the context of total disease, dermatology and a small group was appointed a navy surgeon in the Royal healthcare provision. It was through him I of additional diseases. These are markets Dutch Navy, which was a great experience. was invited for an internship. Vagelos was a of significant potential and unmet need Fresh out of medical school and I was on a visionary but he was also very generous with for patients, comprising over £280bn in ship with 100 sailors going off for an expe- his time – he coached, mentored and coun- total sales for 2015. dition for six weeks at a time. This did two selled me and really helped me get off to a things for me: it allowed me to take care of good start in this industry. n this latest edition of Scrip’s executive the health and safety of 100 crew members, profile series, Hogenhuis discusses with which taught me it is not just about what you LE: Can you explain a bit more about what ILucie Ellis GSK’s big plans for 2018 and know but it’s communication that is critical to your current role is at GSK? onwards, his most difficult moments work- understanding a patient when they come to VH: From all of my professional experience ing in pharma and his top tips for leading a you; secondly it taught me early on about the so far I had learned that getting the right global business unit within an ever evolving need for accountability within a team. Expe- medicine to the right patient in the right way company and expanding industry. riencing the power of a team was something relies on much more than just great science I really enjoyed learning on a ship. Plus it was or developing the right drug. It depends on LUCIE ELLIS: What key things do you a great way of seeing different cultures and how that drug is developed, how it is mar- think shaped you growing up? exploring other parts of the world. keted and a variety of political, economic, VLAD HOGENHUIS: Three things come commercial and social factors. I am lucky in to mind. Firstly, I grew up in a family of LE: From that experience being in the that I have a background that helps me un- physicians: my great grandfather, grand- Navy, what was your next step? derstand this wider picture, and that makes father, father, some of my uncles and my VH: After the Navy I spent a lot of time think- this role such a good fit. brother were all physicians. When I turned ing about how care is delivered. This led The specialty franchise I head up compris- 17 I decided I was going to become a doc- me into my next role as a National Institute es seven therapeutic areas: cardiovascular, tor too. It’s not just about the science for of Health fellow at the New England Medi- neuroscience, immunology, oncology, infec- me but also about caring for patients. cal Center in Boston, working in outcomes tious disease, dermatology and a small group The second aspect that’s really important research. In this position I got to further un- of additional therapeutic areas. My job is two- is the international family I grew up with. I derstand the rigor of science and the impor- fold: firstly I am responsible for our interaction speak five languages; my father is Dutch, my tance of how care is best delivered to the pa- with the markets on a global basis, what we mother is French Russian, I was born in the tient, in considering resources, privatization call LOCs, Local Operating Companies, to en- States but grew up in the Netherlands and and the value to society. This really helped sure that we understand the context, com- this all makes me kind of a “global citizen.” me understand that there’s so much more to petitive, payer and physician needs those There are always lots of languages being medicine than the science; how solutions are LOCs operate within and to provide global spoken around our kitchen table and loads provided is just as important, ensuring an un- strategy and the resources to execute that of cultures being compared. It really is some- derstanding of the total healthcare environ- strategy. The second part of my job is to work thing I hold dear today, working in different ment. This job helped me to identify the role very closely with the manufacturing and the cultures, with different people, in various pharmaceutical companies can play in the R&D organization to ensure they have the countries and speaking their languages. context of total healthcare delivery. best view of where the opportunities lie in And the third part is that despite this cos- the future, where the competition is, what mopolitan background, I grew up in a very LE: Was this the point where you thought the payer needs are and what the patient small town of less than 30,000 inhabitants. you were going to make a career in the phar- needs are so that they are fully equipped to This taught me an awful lot about com- ma industry? develop the best medicines for the future. I munity relationships: it’s all about working VH: It was at the end of that job I actually have a group of about 30 to 40 individuals together. You help another person, another got a call from former Merck CEO, Dr. Roy Va- working in these different therapeutic areas

12 | Scrip intelligence | 5 August 2016 © Informa UK Ltd 2016 HEADLINE NEWS ensuring we have one approach to the spe- next CEO of the company following Sir An- a new medicine to this therapeutic area as no cialty franchise because whereas all of the drew Witty’s departure? new drug had been introduced for the last 50 needs in the different therapeutic areas are VH: Sir Andrew, our current CEO, has had a years. With the significant efforts of our col- different, our approach to specialty is very, tremendous amount of accomplishment leagues in the US, as a company, we’ve been very similar across the spectrum. over the last eight years as head of GSK, so able to reach over 33,000 patients. when I think about the new CEO I would really LE: Do you think this integrated approach is LE: On the flip side, what’s been the most dif- like to see somebody who is global. As we all different to the way other companies work? ficult moment for you? know, opportunities are not limited to the US, VH: Different companies approach chal- European markets and Japan but in a signifi- VH: The most difficult time for me was ac- lenges in different ways. Some companies cant portion of the developing and emerging tually switching companies from Merck to have a very dedicated unit for individual markets. I’d really like to think that the new GSK. I’d been with my former company for areas and others are more decentralized. chief exec would be open-minded – change about 18 years before accepting the role at What we’re trying to do at GSK is the best in our industry is rapid, it’s frequent and can GSK. I didn’t realize at the time how much of both worlds. To be successful you need be brutal so we need to be open-minded. The change I would go through. My family had to have a team of specialists who really new CEO also needs to be a “people person,” to relocate from one country to another, understand this dynamic market, all the here at GSK we are very proud of our prod- we had to learn about another culture; and way from development, up until the point ucts, but we are also all about being a com- then I was also learning a new business of communication to physicians and pa- munity that works together. culture at GSK. I underestimated the chal- tients when a product reaches the market. lenge but I was really blessed with good Given that the price points are often high- LE: You were previously at Merck & Co, can management and a great team. We really er in specialty, you need to be sure that you think of any particular skills you brought pulled it off in defining a new vision, agree- your value proposition for payers is crystal with you to GSK? ing what behaviors would be needed to clear, in terms of which patients will ben- VH: At Merck I had the opportunity to be execute on that vision and also things that efit and should be considered for reim- head of marketing and strategy in China and we wanted to stop doing. bursement and you need a strong medical led four business units. At that time there LE: Tell us something surprising about you team to be able to answer any physician were significant unmet needs in China that that people don’t know. queries accurately and swiftly. Further- we could fulfil. It was also a great opportu- more, patients are often supported by nity to enjoy learning a new culture and a VH: I really love high altitude trekking; I spent highly organized patient groups who can new language. Really early on I felt I needed time in the Himalayas with my wife trekking help us better understand their needs. We to learn Chinese to interact effectively, espe- for three weeks going from village to village. decided to form this specialty franchise to cially with physicians. I’ll tell you about one I have also been on trips with my family to serve the needs of the patients wherever of my most memorable times: I had been the French Alps and the Sierra Nevada in Cali- the geography is, whatever the therapeu- asked to speak in Chinese at a Cardiovascular fornia. It’s just such a great energy builder to tic area is, in a consistent way. Society meeting and foolishly I accepted the go with your family or your loved ones from opportunity. As the evening approached and point A to B enjoying the landscape, enjoying LE: Where do you see GSK in five to ten years’ my time to speak came up – I was following a the mountains. Not having any cell phone time and where would you like to be? couple of native speakers – I really started to reception and no data is probably the most VH: We are going in a targeted direction, ex- sweat buckets. I spoke for about five minutes, liberating part. ecuting the strategy for the three core busi- it wasn’t the prettiest of speeches but when LE: Finally, if you could meet anybody dead nesses, but we still have work to do. We have I sat down afterwards next to a Chinese phy- or alive who would that be and why? had initial successes but we will be deliver- sician he told me he wouldn’t have wanted ing on this strategy for the next two to three to do what I had after only a few months in VH: The person I would love to meet years. Longer term, by 2020, we’ve been very the country. So I felt comforted that even if I would be Johan Cruyff. He was the captain clear that we want our new products to be had been the entertainment for the evening, of the Dutch soccer team that did really a large portion of our total turnover and it was something I would do again. That oc- well in 1974, he died three months ago GSK is well on its way to executing on that casion taught me about the power, if you will, because of lung cancer, and not only was and achieving about £6bn in sales for these of understanding and speaking the language he brilliant at playing football he was also recently launched drugs by 2018. If you look in a local culture. a leader. He has written a couple of books further than 2020 I think we’ll see novel ways about how being successful in soccer is LE: That sounds like an important moment of interacting with patients coming to the not just about your technical skills it’s also for you, but what would you pick as the fore. I’m very excited about the pipeline we having the ability to anticipate where the proudest moment in your career? have communicated and about advances in ball is going to be, and it’s about leader- immunology, nephrology and dermatology VH: Recently we’ve been very successful in ship, nobody is above the team, everybody that will take the spotlight shortly. bringing Benlysta, a medicine for lupus dis- works for the team and it’s about you as a ease, to patients. As a team we’ve worked leader showing the example to the rest of LE: To move forward with this strategy, what hard on educating physicians about the dis- the team to achieve the success. skills or qualities would you like to see in the ease and we’ve been really proud of bringing Published online 26 July 2016 scripintelligence.com 5 August 2016 | Scrip intelligence | 13 BUSINESS BULLETIN

Another Strong Quarter For AbbVie Questions Hang Over Sanofi’s Diabetes With continued strong growth for Hu- Franchise mira, AbbVie Inc. doubles down on con- fidence to protect the franchise with “A somewhat challenging quarter,” was how Sanofi CEO Olivier Brandi- IP strategy. Imbruvica and Viekira Pak court described the second three months of 2016, but analysts say there show growth, although the latter is were no surprises in the downward trajectory of Sanofi’s fortunes. There was also little news on Sanofi’s pursuit of Medivation. Sanofi reported a flourishing only ex-US. The narrative decline in net profit of 11% to €1.16bn for the second quarter of 2016 com- on AbbVie has been unchanging – it pared with a year earlier. Total sales fell 5% to €8.14bn. Sanofi’s business relies too much on top-seller Humira, net income – its preferred measure of net profit – declined 8.7% to €1.68bn. is clearly behind Gilead in hepatitis C Business EPS dropped 7% to €1.31. Sanofi said it expected business EPS and its cancer portfolio and pipeline, to remain broadly stable at CER, barring unforeseen major adverse events. while promising, aren’t threatening to Pharmaceutical sales were broadly in line with expectations at €7.35bn overtake competitors like Bristol-Myers “with stronger Specialty Care and Rare diseases sales and lower erosion of Squibb Co. or Merck & Co. Inc. To that Diabetes sales offsetting slightly weaker Oncology and Consumer Sales,” familiar litany, AbbVie continued its noted Credit Suisse analysts. “As it is a measure you are all interested in, recent success July 29, reporting a sixth I will point out that our global diabetes franchise declined by 3.2% in the consecutive quarter of double-digit sales quarter,” Brandicourt said helpfully in a conference call accompanying the growth, paced by continued increas- earnings presentation. However, less helpful was the lack of information ing sales of Humira. The Chicago-area on how Sanofi planned to tackle pricing discussions for Lantus in light of pharma brought in $6.432bn in global the upcoming biosimilar challenge from Eli Lilly in the form of Basaglar. net revenue during the second quarter [email protected], 29 July 2016 of 2016, up 18.0% year-over-year, with Humira (adalimumab) reporting 17.7% growth and global sales of $4.149bn. [email protected], 29 July 2016 point inhibitors. Merck reported sales of inflammation and immunology (I&I) in $314m for Keytruda in its second-quar- 2010, with apremilast as an anchor; at ter earnings release July 29, in line with the time, management said it believed the Merck Defends Its Offensive expectations. drug could become a $2bn to $3bn seller, [email protected], 29 July 2016 though many investors were doubtful. Strategy For Keytruda [email protected], 28 July 2016 While Merck & Co. Inc.’s Keytruda con- tinues to trail Bristol-Myers Squibb Co.’s Celgene’s Otezla Shines Opdivo and most of its sales continue to GSK Foresees Return To Celgene Corp.’s Otezla (apremilast) is derive from the melanoma indication, Emerging Markets Growth the firm believes it can build its position expected to become a blockbuster seller in the checkpoint race with the first- this year, surpassing sales of $1bn, man- The second quarter saw continued de- mover advantage in first-line lung cancer agement said during the company’s sec- clines in GlaxoSmithKline’s China and and a “huge wall of data” it hopes will ond quarter sales and earnings call July wider emerging markets business, but insulate the drug from follower competi- 28. The drug would become the com- CEO Andrew Witty expects a return to tors and potential price wars later on. pany’s fourth blockbuster franchise and growth in these sectors over the remain- Merck had the first-to-market advantage the first outside of Celgene’s specialty der of the year. The UK-based group’s with its PD-1 inhibitor Keytruda (pem- in oncology. Sales of the psoriasis drug total emerging market pharma sales brolizumab), with approval for meta- increased 170% in the second quarter to slumped by 9% in the quarter, dragged static melanoma in October 2014. But $242m, giving the blood cancer special- down by a 14% fall in China, due largely Bristol’s Opdivo (nivolumab) was cleared ist a strong anchor as it looks to expand to business changes and price reductions for the same indication two months lat- in inflammation and immunology. The in this market. Witty said during a results er, and went on to nab the first approval oral drug was approved in the US and Q&A session that “EMs [emerging mar- in second-line non-small cell lung cancer Europe to treat active psoriatic arthritis kets] are actually improving underlying and continues to rack up more indica- and moderate-to-severe plaque psoriasis but we have had a number of disposals tions. Both drugs are now approved in in 2014 and is a key product in the com- this year, [on top of] the Venezuela [eco- second-line NSCLC and are moving into pany’s strategy to expand beyond its cor- nomic] situation and the continued re- the frontline setting; lung cancer is the nerstone therapy Revlimid (lenalidomide). shaping of China.” largest market for the immune check- Celgene unveiled plans to expand into [email protected], 29 July 2016

14 | Scrip intelligence | 5 August 2016 © Informa UK Ltd 2016 HEADLINE NEWS

Is Monsanto A Mistake When Pharma Is Bayer’s Leading Business? LUCIE ELLIS [email protected]

Second-quarter earnings results have around the Monsanto deal and the ap- ness once its leading drug Xarelto reach- raised questions about Bayer AG’s long- propriate price to pay for that business. In es the end of its patent life. “People are term strategy, including over how long mid-July Bayer increased its all-cash offer getting very concerned about the close- the company’s pharma unit can continue for Monsanto from $122 to $125 a share, ness of the patent cliff for Xarelto but to come out on top and drive the group putting the price tag for the US business this is nine years away at least in the US,” based on the performance of just five “re- at €49.5bn. Bayer’s chief said. Bayer expects Xarelto cently” marketed drugs. “Furthermore, when Bayer launched to lose patent protection in the US, its its offer the company pointed to its track biggest market, in 2024 or possibly 2025 n the back of mixed second-quar- record in M&A, of which the acquisition if it is successful in securing a pediatric ter results it would seem Bayer AG of the Merck OTC business is the most indication. Oneeds to readdress its business pri- recent major example. [The second quar- Xarelto, which is approved for the treat- orities: perhaps to focus on further growth ter’s] weak performance in OTC will raise ment of venous thromboembolism (VTE) of its strong innovative Pharma unit through questions about Bayer’s ability to deliver creative partnerships and in-house R&D in- on sales and cost synergies in major deals,” Xarelto’s patent vestment, instead of conducting massive Berenberg analysts said. acquisitions in its failing CropScience and Meanwhile, the Pharma unit was dubbed expiry is at least nine struggling Consumer Health units. “the highlight of 2Q” by analysts. Anticoag- ulant product Xarelto (rivaroxaban) alone years away in the US saw sales of €703m in the second quarter, beating expectations by 6%. For its group of “recently launched products,” including and stroke prevention in atrial fibrillation Xarelto, the eye medicine Eylea, cancer (SPAF), is expected to reach peak world- drugs Xofigo and Stivarga, and Adempas wide sales of €5.7bn by 2022, according to to treat pulmonary hypertension – which Datamonitor Healthcare. are starting to become more established drugs now – Bayer is predicting full-year KEY 2Q NUMBERS sales of €5.5bn, up from €5bn previously. • Group revenues: €11.83bn (+2.3% CER);

Shutterstock: Shutterstock: Watman Anton Eylea (aflibercept) was Bayer’s second best- consensus forecast: €12.18bn) performing product for the quarter, pro- • Pharma sales: €4.10bn (cons: €4.04bn) For yet another quarter Bayer’s Pharma ducing sales of €418m that beat consensus • Consumer Health sales: €1.55bn (cons: unit has driven profits and growth for estimates by 6%. €1.59bn) the whole company, while its Consumer Though the immediate future looks • CropScience sales: €2.52bn (cons: €2.71bn) Health and CropScience units both missed bright for the Pharma unit, concerns are • Animal Health sales: €426m (cons: €438m) sales expectations and posted disappoint- focused on the sustainability of this perfor- Bayer has lowered its sales expectations ing results for 2Q 2016. Bayer has also up- mance. When asked to explain why Bayer for the full-year to €46bn-47bn, having dated its full-year expectations for all busi- is pursuing such a high monetary deal in previously expected more than €47bn. ness units, for which it is now anticipating a CropScience as opposed to investment or Underlying EBITDA for 2Q 2016 was €3bn, low-single-digit percentage decline for the transactions in healthcare, Bayer’s new CEO a beat of 4% that was accredited to the CropScience business for 2016. Werner Baumann gave a fluffy response. strength of the Pharma business with help Despite these weak results in Crop- Baumann, for whom the second quarter is from good numbers from Covestro (its Science, Bayer is currently pursuing a his first quarterly report as chief executive materials manufacturing business), offset- merger with US genetically modified seeds of the business after taking up the role in ting poor performance by the Crop and business Monsanto – which currently rep- April, simply said that there was a “sound Consumer units. Full-year EBITDA guid- resents the largest ever acquisition bid by and logical rationale” behind the Monsanto ance has been raised to high single-digit a German company. But Monsanto also deal and that the company’s current deci- growth from mid-single digit growth. Core missed expectations for the second quar- sion not to pursue a large transaction in EPS for continuing operations is now ex- ter of the year, underlining the difficult the healthcare sector is a “complex” discus- pected to grow at mid- to high single dig- market conditions in this sector. Analysts sion for another time. its, previously expected to be mid-single at Berenberg Bank highlighted that Bayer’s Baumann also dismissed trepidations digit growth. poor 2Q results have increased uncertainty over the future of Bayer’s Pharma busi- Published online 27 July 2016

scripintelligence.com 5 August 2016 | Scrip intelligence | 15 INFOGRAPHIC

Watson Pharmaceuticals/Actavis/Allergan 2014 GROWTH OF A Forest Laboratories Inc. 2015 2012 in May; Forest had Australia-based acquired Aptalis Pharma, Auden Mckenzie Holdings Ltd., a 2000 2011 Ascent a specialty pharma Schein Pharmahealth Ltd. company focused on UK-based company Pharmaceutical Inc. Greece's Specifar 2013 gastrointestinal focused on Pharmaceuticals SA disorders and cystic development, 2012 Belgium-based brosis in February and licensing and GIANT Uteron Pharma SA, had announced marketing of niche Teva is about to acquire Allergan's Switzerland-based Actavis Group and which has a pipeline acquisition of GI-focused generic medicines generics business for roughly 2009 adopts Actavis name of women's health Furiex Pharmaceuticals and proprietary products Inc., which was brands $40.5bn, the largest generics deal 1983 Arrow Group completed in July. in history. The two entities have founded by 2013 2015 each grown through numerous Allen Chao, PhD, and David Irish company Allergan PLC and acquisitions over the past two 2014 changes its name to Hsia, PhD 2006 Warner Chilcott PLC decades. Here are the deals that and relocates Durata Allergan; US generics Andrx Corp. headquarters to Therapeutics Inc. business continues to have made them dominant players Ireland operate as Actavis in the generics space. 1983 2015

Teva Pharmaceutical Industries Ltd. 1992 2008 2014 Purchases W.R. CoGenesys Inc., a NuPathe Inc., Grace's 50% division of Human gaining the 2016 Genome Sciences Inc. prescription 1985 share of TAG 1996 Representaciones e 1951 Pharmaceuticals migraine patch Investigaciones Forms 50-50 and together Zecuity (sumatriptan Becomes Teva Purchases UK's 2008 Médicas S.A. de C.V. joint venture with Lemmon third largest iontophoretic (Rimsa), a leading Middle East with W.R. Grace creates Teva Spain's Bentley transdermal system) Pharmaceutical generics company 2011 pharmaceutical 1980 to form TAG Pharmaceutical APS/Berk from Pharmaceuticals Inc. manufacturing and Chemical Works Pharmaceuticals; USA Inc. Taiyo Company Ltd. Rhone-Poulenc 2014 distribution company Israel's leading the joint venture Rorer 2008 Pharmaceutical in Mexico drug manufacturer acquires 2004 Industry Co. Ltd. Labrys Biologics Inc., in Japan Ikapharm and Lemmon Co. Sicor Inc. Barr a private start-up 50% of chemical in Sellersville, 1996 Pharmaceuticals developing a novel manufacturer PA, which gives Inc., including its 2011 migraine prophylaxis Plantex Ltd. from Teva entry into Biocraft European treatment Koor Industries U.S. market Laboratories Inc. subsidiary PLIVA Cephalon Inc.

1901 2016

1976 1995 2000 2015 Teva merges with 1989 Hungary's Biogal Novopharm Ltd., 2010 1901 Assia and Zori to Pharmaceutical second largest Auspex Pharmaceuticals S.L.E., predecessor of create Teva remaining 50% of Works Ltd. producer of ratiopharm, Inc., which is developing Germany's deutretrabenazine for Teva named after its Pharmaceutical Israel's API producer 1999 generics in Industries Ltd. Plantex Canada second largest potential treatment of chorea three founders, is Copley generics 2013 associated with Huntington's established in Jerusalem Pharmaceutical disease, tardive dyskinesia producer MicroDose Inc. and Tourette syndrome Therapeutx, a drug delivery 1998 2006 company focused Netherlands-based IVAX Corp. on inhalation Pharmachemie BV technologies Founded Purchased Acquired Merged Formed Became

16 | Scrip intelligence | 5 August 2016 © Informa UK Ltd 2016 INFOGRAPHIC

Watson Pharmaceuticals/Actavis/Allergan 2014 GROWTH OF A Forest Laboratories Inc. 2015 2012 in May; Forest had Australia-based acquired Aptalis Pharma, Auden Mckenzie Holdings Ltd., a 2000 2011 Ascent a specialty pharma Schein Pharmahealth Ltd. company focused on UK-based company Pharmaceutical Inc. Greece's Specifar 2013 gastrointestinal focused on Pharmaceuticals SA disorders and cystic development, 2012 Belgium-based brosis in February and licensing and GIANT Uteron Pharma SA, had announced marketing of niche Teva is about to acquire Allergan's Switzerland-based Actavis Group and which has a pipeline acquisition of GI-focused generic medicines generics business for roughly 2009 adopts Actavis name of women's health Furiex Pharmaceuticals and proprietary products Inc., which was brands $40.5bn, the largest generics deal 1983 Arrow Group completed in July. in history. The two entities have founded by 2013 2015 each grown through numerous Allen Chao, PhD, and David Irish company Allergan PLC and acquisitions over the past two 2014 changes its name to Hsia, PhD 2006 Warner Chilcott PLC decades. Here are the deals that and relocates Durata Allergan; US generics Andrx Corp. headquarters to Therapeutics Inc. business continues to have made them dominant players Ireland operate as Actavis in the generics space. 1983 2015

Teva Pharmaceutical Industries Ltd. 1992 2008 2014 Purchases W.R. CoGenesys Inc., a NuPathe Inc., Grace's 50% division of Human gaining the 2016 Genome Sciences Inc. prescription 1985 share of TAG 1996 Representaciones e 1951 Pharmaceuticals migraine patch Investigaciones Forms 50-50 and together Zecuity (sumatriptan Becomes Teva Purchases UK's 2008 Médicas S.A. de C.V. joint venture with Lemmon third largest iontophoretic (Rimsa), a leading Middle East with W.R. Grace creates Teva Spain's Bentley transdermal system) Pharmaceutical generics company 2011 pharmaceutical 1980 to form TAG Pharmaceutical APS/Berk from Pharmaceuticals Inc. manufacturing and Chemical Works Pharmaceuticals; USA Inc. Taiyo Company Ltd. Rhone-Poulenc 2014 distribution company Israel's leading the joint venture Rorer 2008 Pharmaceutical in Mexico drug manufacturer acquires 2004 Industry Co. Ltd. Labrys Biologics Inc., in Japan Ikapharm and Lemmon Co. Sicor Inc. Barr a private start-up 50% of chemical in Sellersville, 1996 Pharmaceuticals developing a novel manufacturer PA, which gives Inc., including its 2011 migraine prophylaxis Plantex Ltd. from Teva entry into Biocraft European treatment Koor Industries U.S. market Laboratories Inc. subsidiary PLIVA Cephalon Inc.

1901 2016

1976 1995 2000 2015 Teva merges with 1989 Hungary's Biogal Novopharm Ltd., 2010 1901 Assia and Zori to Pharmaceutical second largest Auspex Pharmaceuticals S.L.E., predecessor of create Teva remaining 50% of Works Ltd. producer of ratiopharm, Inc., which is developing Germany's deutretrabenazine for Teva named after its Pharmaceutical Israel's API producer 1999 generics in Industries Ltd. Plantex Canada second largest potential treatment of chorea three founders, is Copley generics 2013 associated with Huntington's established in Jerusalem Pharmaceutical disease, tardive dyskinesia producer MicroDose Inc. and Tourette syndrome Therapeutx, a drug delivery 1998 2006 company focused Netherlands-based IVAX Corp. on inhalation Pharmachemie BV technologies Founded Purchased Acquired Merged Formed Became

scripintelligence.com 5 August 2016 | Scrip intelligence | 17 POLICY & REGULATION BRIEFS

Large Employer Drug Contracting Block Could Chinese Stamp On Indian Pharma Challenge Manufacturers The Fosun group led by its billionaire chair Guo Guangchang has snapped up the injectables firm Gland for around $1.26bn, the first mega Chinese Express Scripts has been talking to buy in the Indian pharmaceutical space. The deal opens up many potential members of the Health Transforma- collaborative opportunities, though it remains to be seen how smoothly tion Alliance about negotiating pricing it sails through in the Indian regulatory maze. Fosun Pharma and Fosun on behalf of the group, which includes International Ltd. are acquiring 86.08% in India’s Gland Pharma Ltd. for 20 large employers providing health up to $1.26bn. The Chinese group will buy approximately 79.9% equity benefits for four million individuals. interest in Gland and subscribe to convertible preference shares to be is- Collective prescription drug contract- sued by the Hyderabad-based company representing an additional 6.083% ing by a group of large private em- equity interest. The deal closing is subject to regulatory approval from ployers that have formed the Health antitrust authorities of India and the US and India’s foreign investment Transformation Alliance could pose authorities – a potentially tricky area going by early reactions from some challenges for both manufacturers Indian industry experts. “The FIPB [India’s Foreign Investment Promotion and pharmacy benefit managers. For Board] will probably take a good hard look at the deal; it’s an injectables manufacturers, a group of up to 20 unit, a Chinese acquirer, even though much of it is said to be for exports,” an expert told Scrip. India’s new liberalized foreign direct investment policy permits up to 74% FDI via the automatic route in brownfield pharmaceuti- cals, though government approval is necessary beyond this threshold. [email protected], 29 July 2016

changes in the way employers contract how many products FTC might require with PBMs. The 20 large employers Teva to divest before clearing the un- managing insurance for four million ion of the two generic drug units. As it individuals have banded together to turns out, FTC’s blessing carries a high lower health care costs by leveraging price: the agency is requiring substan- the information and experience of its tial divestments, including the sale of members. Formation of the group was 79 pharmaceutical products to eleven announced in early 2016 and the drug different firms. The agency’s action rep- pilot will be its first project. resents the largest drug divestiture ever Shutterstock: RomanR Shutterstock: [email protected], 26 July 2016 ordered by FTC in a pharmaceutical merger review, the agency said. The di- employers covering millions of peo- vestments are significantly greater than ple would wield significant leverage in FTC Clears Teva/Allergan Teva originally anticipated. During its contracting negotiations. Members of Generics Deal financial update July 13, management the organization include companies said the proceeds generated from the such as American Express, Coca Cola The news Teva Pharmaceutical In- sale of products would be significantly and IBM. For PBMs, representing a dustries Ltd. investors have been an- greater than Teva had originally fore- block of business that size would of- ticipating has come to pass: the Israeli cast, about $2.9bn versus $400m. Teva fer a significant business opportunity pharmaceutical company’s $40.5bn is the biggest generic drug company in but also would come with substantial acquisition of Allergan PLC’s generic the US with an overall generic market pressure on rates and fees. On the other drug unit was cleared by the Federal share of approximately 13%, while Al- hand, if the alliance decides to bypass Trade Commission July 27. Investors lergan is third, with approximately a 9% the use of PBMs, it could set a prec- were anxiously waiting FTC’s blessing, market share, according to FTC’s state- edent in the marketplace that could and growing increasingly concerned ment. The merged company would threaten the PBM business model. The about a potential hang up after Teva have a roughly 22% share of the generic Health Transformation Alliance plans pushed back the timeline for a closing drug market. The combined company to launch a pilot program in 2017 with several times, most recently on July 13, is expected to generate $26.7bn to the goal of lowering prescription drug when the company also updated its $27.8bn in revenues in 2019, up from costs. The group has not released spe- mid-range guidance. Management has the $19.7bn Teva generated as a stan- cifics on how the program will be struc- insisted all along that the closing was dalone business in 2015. tured but has indicated it might involve on track, but one question has been [email protected], 28 July 2016

18 | Scrip intelligence | 5 August 2016 © Informa UK Ltd 2016 STOCKWATCH

The Iceberg Beneath Gilead ANDY SMITH

Gilead was among the companies that drug pricing controversy has restricted Gil- gressively squeezing them down on price. reported 2Q results last week but left ead’s ability to increase the price of its HCV We are likely years away from the next investors wondering what more lay be- antivirals resulting in lowered expectations sustained upturn in the biotech cycle so neath the announcements. At this point of its future earnings growth. Overlooked is in the meantime, while Gilead’s valuation in earnings season, investors’ models are the fact that Gilead’s quarterly sales are 3.6 decays, it is hopefully at a slower rate than as current as they can ever be, but uncer- times what they were before the Pharmas- those smaller targets it could acquire with tainty still prevails. set acquisition. its $25bn cash pile and $5bn in quarterly Despite achieving about 90% market operating cash flow. ilead Sciences Inc.’s. headline sec- share in HCV antivirals and pushing Vertex Other companies saw their stock prices ond-quarter earnings announce- Pharmaceuticals Inc. and soon Johnson rise after reporting their second-quarter re- Gment included a sales and earnings & Johnson out of the market, investors’ sults last week even though they face same beat of analysts’ consensus estimates that response to Gilead’s sales and earnings issue as Gilead. was quickly forgotten because of a rare beat – which was driven by that old stal- Amgen Inc., like Gilead, beat analysts’ cut in full-year guidance. The $300m short- wart; the HIV franchise – is again ‘so what?’ consensus estimates of sales and earnings fall in expected sales from its HCV antiviral Once again it is the limited visibility of what and then, unlike Gilead, raised its full-year franchise – which was carried through to its comes next – if anything – that is eroding guidance. full-year guidance – prompted an 8.4% de- Gilead’s valuation. Although the headline results were cline in Gilead’s share price over the week, in described as “solid” by the analysts from contrast with the NASDAQ Biotech Index’s The valuation of Gilead Piper Jaffray, most other analysts I read (NBI) 3% rise. The expectations of Gilead’s has for some time noted that the results had been achieved future earnings growth – as reflected in its for the second quarter running by price price to earnings ratio of less than 7.0 – are been the source of rises and inventory build against the now so low that the analysts from Leerink backdrop of volume declines. As with Partners had to exclude it in their analysis of consternation amongst Gilead, questions are being asked about the growth outlook for large capitalization investors and analysts what Amgen is going to buy with its biotechs so as not to make the sector look $35bn cash pile. Amgen’s share price too cheap. finished the week up 3.7% in response The valuation of Gilead has for some time to its financial results in deference to its been the source of consternation amongst For at least the past nine months sell-side Gilead-like challenges. investors and analysts. JP Morgan’s increas- analysts have been asking the questions Rarely has earnings season exposed a ingly poignant question for about the last about Gilead’s next acquisition targets and cumulative need in the life sciences sector six months has been “Gilead, value stock the responses they have been getting have for a valuation-stringent approach to M&A. or value trap?”. Value traps are investments been non-specific and opaque. On the one While the residual perspective from last or assets that appear comparatively cheap hand Gilead is not stupid enough to dis- summer’s market peak may still be restrain- and attract bargain hunters, but because close which companies they are thinking ing this bolus of activity, the good news is of either structural or company-specific is- about acquiring, but on the other, no news that a golden period of M&A will ultimately sues their growth remains constrained. For is bad news as far as many investors have occur. The alternative for the sector is not example, had you bought a VCR/VHS re- been concerned. Hence my focus on what worth thinking about. corder early last week because the format is happening below Gilead’s waterline. In The Magna Biopharma Income fund was cheap, the announcement that the order to hold the stock, investors have to holdings include Gilead and Amgen. last factory is about to close would have assume that significant potential transac- Andy Smith is chief investment officer of left your investment value trapped. tions are under discussion. There are, how- Mann Bioinvest. Mann Bioinvest is the in- Investors have been here before with ever, grounds for optimism since we are vestment adviser for the Magna BioPharma Gilead. I remember attending an investor only about a year away from the all-time Income fund which has no position in the dinner in 2010 where Gilead’s plans for high in the NBI. Many management teams stocks mentioned, unless stated above. Dr the expansion of its already dominant HIV have commented on the inability of the Smith gives an investment fund manager’s franchise with single-dose tablets of four boards of companies that they would like view on life science companies. He has been components were greeted with a ‘so what?’ to acquire to accept that valuations have lead fund manager for four life science– response from many investors. Ironically, changed since last summer. My aspiration specific funds, including International Bio- that ‘so what?’ was the acquisition of Phar- and expectation for Gilead is that beneath technology Trust and the AXA Framlington masset Inc. that brought Gilead a second the surface, its global corporate develop- Biotech Fund, and was awarded the Tech- industry-leading antiviral franchise in HCV ment matrix is in constant discussions nology Fund Manager of the year for 2007. but kicked off the drug pricing debate. The with the next Pharmasset and that it is ag- Published online 1 August 2016

scripintelligence.com 5 August 2016 | Scrip intelligence | 19 EXPERT VIEW

Biosimilar Confidence And Knowledge Needed In Europe, Say Experts European biosimilar market penetration varies widely across the EU member states and disease groups, with different government policies on promotion, purchasing and communication leading to mistrust. IAN SCHOFIELD [email protected]

he European Commission is looking to boost confidence in biosimilars to support their uptake on a much wider scale T across Europe, and to get a bird’s eye view of what is driving or hindering the EU market for biosimilars. Biosimilar approvals in Europe are going from strength to strength, with 21 products currently holding an EU marketing authorization. As of July 2016, a total of 15 other biosimilar filings were under evaluation at the European Medicines Agency, many of them versions of top selling monoclonal antibody products such as AbbVie Inc.’s Humira (adalimumab) and Roche’s Rituxan (rituximab). According to Medicines for Europe, which represents firms mar- keting generics, biosimilars and value-added drugs, the biosimilars approved in the EU to date have generated more than 400 million patient days of clinical experience, and Europe is now a leading in- dustrial base for the development of biologics, whether originator or biosimilar. Nonetheless, while Europe is well ahead in terms of biosimilar approvals and the regulatory framework compared with countries like the US, the competitive market landscape in biologicals leaves Balazh Anton Shutterstock: much to be desired. And while biosimilars are seen as a valuable source of savings Among the factors causing these variations are differences in for healthcare systems as populations age and healthcare systems government policies on promoting biosimilars, differing approach- come under increasing pressure, uptake of biosimilars and levels of es to purchasing and procurement, and a lack of reliable informa- patient access in Europe still vary widely as a result of factors like tion and communication to physicians and patients that can result payer attitudes, physician incentives, information and education, in mistrust of biosimilars. In some countries it has been difficult to and originator pricing policies. assess the situation properly because of the lack of data on market shares, local factors affecting biosimilar uptake, and so on. For these reasons, the European Commission is currently running ‘By 2010 both sides of the industry, an initiative to boost confidence in and knowledge of biosimilars in order to support their uptake on a much wider scale across Europe, originators and generics, had moved and to get a bird’s eye view of what is driving or hindering the EU market for biosimilars. into the biosimilar market but In June, the Commission held a multi-stakeholder workshop in patients knew nothing about it, Brussels to look at the current biosimilar competitive situation as well as the need to improve information provided to patients and nor did doctors’ healthcare professionals. At the June 20 workshop, speakers from various EU countries discussed the outstanding issues, the role of patients, and national projects in areas such as biosimilar switching. Some countries have taken steps to boost biosimilar use, notably But as Hilda Juhász, policy officer at the Commission’s internal Norway with its decision to switch Remicade (infliximab) patients en market and industry directorate explains, this event was just the masse to the biosimilar version via the tender process, and Poland, latest step in a process that has its origins in the 2005-2008 “Phar- where uptake of infliximab has been quick because of the use of maceutical Forum” and later became the 2010-13 EU process on the tendering system and encouragement of substitution. Biosimi- corporate responsibility and access to medicines. As part of this lar infliximab is also performing strongly in terms of market share in process, a working group on market access and uptake of biosimi- countries like Bulgaria and Denmark. But biosimilar market penetra- lars was established to address issues and uncertainties around the tion varies widely across the EU member states and disease groups, growing biosimilars market. with G-CSF products, for example, faring well in most countries, but By 2010, “both sides of the industry, originators and generics, had follitropin alfa often gaining only single-digit market shares. moved into this market but patients knew nothing about it, nor

20 | Scrip intelligence | 5 August 2016 © Informa UK Ltd 2016 EXPERT VIEW

did doctors,” says Juhász. “So we set up a working group, which was savings can be achieved even if biosimilar uptake is low, and price good as there was a need for all stakeholders to work together on reductions can be secured through price regulation interventions this,” she told Scrip in an interview. and/or commercial decisions by manufacturers. Even if the biosimi- “One thing we realized early on was that we didn’t know about lar is not always the one that is sold, its presence on the market “is the uptake of biosimilars in the member states – in some there is likely an essential step to generate a more competitive environ- good uptake, in others zero or just a little, but we didn’t know the ment, which leads to lower prices.” factors affecting uptake. There was also a lack of unbiased informa- Competition influences originator behavior in different tion, and a lot of confusion with regard to terminology, the scien- ways: in many cases, biological originators have behaved differ- tific concept of biosimilars and so on.” ently from what was experienced with small molecule products: While the Commission is responsible for issuing marketing au- either maintaining the price of cutting it based on mandatory thorizations for biosimilars, its remit does not extend to issues of price regulations. However, in the biosimilars area there has access in the member states, and the aim in steering this access been “a multitude of different behaviors,” the report says. Some initiative is to provide an EU-wide forum where the member states originators have launched innovative long-acting/pegylated and other interested parties can thrash out the issues and share products without a price premium, “changing the treatment experiences of issues like biosimilar switching. paradigm and therefore usage pattern. This has been seen, for As part of this process, at the end of 2013 the Commission example, in Denmark, where “non-accessible” products like Teva published a “Consensus Information Paper”, What you need to Pharmaceutical Industries Ltd.’s Lonquex and Amgen Inc.’s Neu- know about biosimilar medicinal products, prepared by the work- lasta have kept up the originators’ volume market share. Others ing group and addressing questions relating to EU policy and the have effectively reduced their price levels, for example in Swe- regulatory framework as well as questions of interest to patients, den, where the price per treatment day of HGH has fallen more payers and doctors. sharply for the reference drugs than for biosimilars. The following year, the Commission decided it needed more data on actual uptake of biosimilars in the various EU countries. It therefore approached IMS Health to work on what Juhász de- ‘One thing we realized early on scribes as a “pro bono project to help us bring stakeholders to- gether and agree on a set of indicators to describe the market was that we didn’t know about development on a yearly basis, to have more information, and to see in the different countries and disease groups how uptake, vol- the uptake of biosimilars in the umes, prices, etc., are developing.” The aim was also to “see if we can make some observations, for member states – in some there is example whether it is true that if a biosimilar is approved and mar- good uptake, in others zero or just a keted, prices actually drop, and how that works for different kinds of products,” she says. little, but we didn’t know the factors IMS Health Inc. published its first report, The Impact of Biosimilar Competition, in May 2015, looking at the effects on price, volume, affecting uptake’ and market share following the arrival of biosimilar competition in the EEA countries (the EU plus Iceland, Liechtenstein and Norway), with contributions from Medicines for Europe, the R&D-based in- Lower prices increase patient access in countries with low dustry federation EFPIA, and the biotech industry body EuropaBio. initial usage: while some degree of price elasticity is to be ex- The report, which was accompanied by five key observations pected for biosimilars, the report shows different levels of impact and a reading guide with a broad set of key performance indicators of lower prices in different countries and product classes. While (KPIs) for multiple countries, was presented at the first stakeholder lower prices do impact usage, other factors need to be taken into event on Oct. 6, 2015. It was subsequently consolidated and up- account, such as new indications of restriction of indications, gen- dated with 2015 data, and presented by the Commission at the eral economic conditions imposing use restrictions, and changes in second stakeholder event last month. diagnosis and prevalence of disease. As well as examining the situation of available biosimilars in the Product profile differences can explain differences in- im various countries, the report made the following observations: pact on key performance indicators: differences in approved Competition drives down prices: the four established therapy indications are relatively small for HGH and G-CSF, somewhat larg- areas with competition – epoetins, G-CSF, human growth hormone er for EPO, and the largest for the anti-TNFs. “As a result, different and anti-TNFs – show “a consistent picture of reduced average pric- products are used for different indications which impact the pa- es” in the EEA countries, across the whole product class. Portugal tients for which they compete in the class. This is most obvious in showed the greatest price reductions for epoetins in 2015, at -61%, anti-TNF,” the report says. Frequency of administration and mode Slovakia for G-CSF (-59%), Finland for HGH (-47%) and Sweden for of administration also impact competition within a class, for ex- anti-TNFs (-21%). The countries with the highest reduction show a ample more frequent subcutaneous injection in home treatment reduction of 50-70%, the report says. with anti-TNFFs and a less frequent intravenous infusion in the There is a weak correlation between market share and price: hospital setting. data in the report show that in the four established classes, high Published online 26 July 2016 scripintelligence.com 5 August 2016 | Scrip intelligence | 21 PIPELINE WATCH

Scrip’s weekly Pipeline Watch tabulates the most recently reported CLICK late-stage clinical trial and regulatory developments from the more Visit scrip intelligence.com than 10,000 drug candidates currently under active research worldwide. for the entire pipeline with added commentary. Late-stage clinical developments for the week 22–28 July 2016

LEAD COMPANY PARTNER COMPANY DRUG INDICATION MARKET REGULATORY APPROVAL Sanofi Zealand Pharma AS Adlyxin (lixisenatide) type 2 diabetes US Viekira XR (dasabuvir, Enanta Pharmaceuticals hepatitis C genotype 1 and compensated AbbVie Inc. ombitasvir, paritaprevir and US Inc. cirrhosis ritonavir) tablet Apricus Biosciences Inc. – Vitaros (alprostadil) erectile dysfunction Lebanon REGULATORY FILING ACCEPTED BioMarin Pharmaceutical – Brineura (cerliponase alfa) neuronal ceroid lipofuscinosis US, EU Inc. SUPPLEMENTAL REGULATORY FILING ACCEPTED Isentress (raltegravir) once- Merck & Co. Inc. – HIV-1 infection EU daily formulation Ono Pharmaceutical Co. Bristol-Myers Squibb Co. Opdivo (nivolumab) head and neck cancer Japan Ltd. CHMP POSITIVE OPINION ON FIRST APPROVAL Ipsen Exelixis Inc. Cabometyx (cabozantinib) advanced renal cell cancer EU Eisai Co. Ltd. – Kisplyx (lenvatinib) advanced renal cell cancer EU Merrimack Onivyde (pegylated and Shire PLC metastatic pancreatic adenocarcinoma EU Pharmaceuticals Inc. liposomal irinotecan) Allergan PLC – Truberzi (eluxadoline) irritable bowel syndrome with diarrhea EU Sialanar (glycopyrronium Proveca Ltd. – severe sialorrhea EU bromide) Techdow Europe AB – enoxaparin sodium biosimilar venous thromboembolism EU Pharmathen SA – enoxaparin sodium biosimilar venous thromboembolism EU CHMP POSITIVE OPINION ON SUPPLEMENTAL APPROVAL Bristol-Myers Squibb & Co. – Orencia (abatacept) iv and sc progressive rheumatoid arthritis EU Enanta Viekirax (ombitasvir, hepatitis C genotype 4 with compensated AbbVie EU Pharmaceuticals Inc. paritaprevir, ritonavir) tablets cirrhosis Truvada (emtricitabine, Gilead Sciences Inc. – HIV pre-exposure prophylaxis EU tenofovir disoproxil) COMPLETE RESPONSE LETTER Dextenza (dexamethasone) Ocular Therapeutix Inc. – oculur pain post-eye surgery US insert Valeant Pharmaceuticals Nicox SA Vesneo (latanoprostene bunod) glaucoma, ocular hypertension US International Inc. REGULATORY FILING Amgen Inc. UCB SA romosozumab osteoporosis US SUPPLEMENTAL REGULATORY FILING Teijin Pharma Ltd. Ipsen Somatuline (lanreotide) neuroendocrine tumors Japan PHASE III TRIAL INITIATION FibroGen Inc., Astellas Pharma Inc. roxadustat anemia due to chronic renal disease Japan AstraZeneca PLC Tonix Pharmaceuticals TNX-102 SL (cyclobenzaprine) Holding Corp. – sublingual fibromyalgia – PRODUCT LAUNCH Acerus Pharmaceuticals Aytu BioScience Inc. Natesto (testosterone) hypogonadism US Corp. Source: Sagient Research’s BioMedTracker

22 | Scrip intelligence | 5 August 2016 © Informa UK Ltd 2016 APPOINTMENTS

Marathon Pharmaceuticals, LLC, a bi- Array BioPharma, a biopharmaceuti- at Hebrew University and Hadassah along- opharmaceutical company developing cal company focused on the discovery, side his role as CMO of Galmed Pharma. treatments for rare diseases, has made two development and commercialization of senior additions to its executive team. Dr. targeted small molecule drugs to treat Bioniz Therapeutics Inc., a biopharma- Erik Eglite joins the company as vice presi- cancer, has appointed Jason Haddock ceutical company developing peptide dent, chief compliance officer and corpo- chief financial officer. Haddock succeeds therapeutics to treat immuno-inflamma- rate counsel, and will be responsible for David Horin, who had been acting as Ar- tory diseases and cancer, has appointed the company’s compliance matters. Prior ray’s interim CFO; Horin will continue to Dr. David Pyott chair of its board of direc- to joining Marathon, Eglite was was vice provide services to Array on a consulting tors. Pyott is the past chair and CEO of Al- president, chief compliance officer and basis. Previously Haddock held a number lergan Inc. Furthermore, Ilan Zipkin, senior corporate counsel for Lundbeck Pharma- of positions across accounting, planning, investment director of Takeda Ventures, ceuticals. Meanwhile, Eric J. Messner joins commercial, analytical and business de- and Joe Kiani, chair and CEO of medical Marathon as vice president, sales and mar- velopment capacities during his 13 years device company Masimo Corporation keting and will lead the company’s sales, at Bristol-Myers Squibb. But most recently (MASI), have also joined Bioniz’s board marketing and managed care strategy he was CFO and Chief Operating Officer of directors. The appointments were an- and execution. Prior to joining Marathon, (COO) of BERG Health, an oncology fo- nounced in parallel with the news Bioniz Messner was CEO of Anagin, LLC, which cused research, diagnostics and develop- has raised $13m in its series A financing to develops drugs for post-traumatic stress ment company. fund development of its peptide platform disorder and traumatic brain injury. technology. The investment syndicate Galmed Pharmaceuticals Ltd., a clinical- was co-led by Takeda, via its corporate Selecta Biosciences, Inc., a clinical-stage stage biopharmaceutical company focused venture arm Takeda Ventures, and Pyott; biopharmaceutical company developing on the development of a once-daily oral and also includes investments from Kiani targeted antigen-specific immune thera- therapy for the treatment of liver diseases, and Cota Capital. pies for rare diseases, has named Timothy has appointed Professor Ran Oren, chief C. Barabe to its board of directors. Most medical officer. Oren is currently professor Valeant Pharmaceuticals Internation- recently chief financial officer and execu- of gastroenterology and hepatology at the al, Inc. has named Sarah B. Kavanagh a tive vice president for Affymetrix Inc., Bar- Faculty of Medicine, the Hebrew University director of its board. Kavanagh is currently abe has previously held a broad range of of Jerusalem, Israel, as well as the head of the a director and chair of the audit committee financial and strategic roles at a number of Institute of Gastroenterology and Liver Dis- of Hudbay Minerals Inc. and a trustee and life science companies, including Human ease at Hadassah Medical Center, Jerusalem. chair of the compensation and govern- Genome Sciences and Novartis AG. He will maintain his ongoing commitments ance committee of WPT Industrial REIT.

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