In Lung Cancer

4 August 2017 No. 3865

Scripscrip.pharmamedtechbi.com Pharma intelligence | informa • a Phase I asset also in development for SCLC, though trials for this compound, known as 2879552, will continue in acute myelogenous leukemia (AML) and myelodysplastic syndrome (MDS); • retosiban, which is in Phase III for sponta- neous pre-term labor; • three Phase II assets that had been targeting heart failure, cholestatic pruritus and psoriasis.

RARE DISEASE REVIEW The UK big pharma has also undertaken a strategic review of its rare diseases unit and is now considering options for future ownership of these assets. GSK’s rare disease portfolio currently generates sales of around £425m annually. Bernstein analysts said in a Shutterstock: Gajus Shutterstock: July 26 note that the business could fetch between £2bn and £3bn. The corporate changes presented by Walmsley Shakes Up GSK; Walmsley during a three-hour company update in London on July 26 are based on three long-term priorities: innovation, per- Cuts 30 Drug Programs formance and trust. LUCIE ELLIS [email protected] R&D REFURBISHMENT uring the company’s second In a move to “strengthen” its pharma Under its “innovation” priority, in paral- quarter earnings report, GlaxoS- unit, GSK is doing away with more than 30 lel with pipeline divestures, GSK has de- DmithKline PLC’s new CEO Emma development programs that are “unlikely veloped a list of pipeline assets to pour Walmsley outlined key issues for the busi- to generate sufficient returns,” the com- more investment into. This list will evolve ness over the next three years and set out a pany noted in its July 26 2Q report. as data read out, the group noted, but series of new priorities, putting the group’s “GSK has so far made decisions to termi- items currently focus on respiratory and pharmaceutical unit at the top of her to- nate, partner or divest more than 30 pre- infectious disease pipeline programs. GSK fix list ahead of the consumer health and clinical and clinical programs,” the company will pour 80% of its pharmaceutical R&D vaccine units. said, suggesting that other assets may also capital into these two current therapy ar- The new CEO’s corporate overhaul get the cut. eas as well as two more R&D areas seen contains many more fireworks than ana- Programs already confirmed to be termi- as potential growth drivers: oncology and immuno-inflammation. lysts and investors had anticipated. GSK’s nated or divested include: Walmsley said: “We need a significant stock price (London Stock Exchange) was • a Phase II hepatitis C drug; overhaul to how we develop our clinical trending down by around 1.5% in the af- • danirixin, which is in Phase II trials for assets.” GSK’s chief highlighted that the ternoon of July 26 after the company’s influenza; big pharma has fallen behind its rivals long list of corporate changes and cut- • tarexumab, which is in Phase II for small backs were announced. cell lung cancer (SCLC); CONTINUED ON PAGE 7

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

MYSTIC Misses A Whopper Of A Deal Quarterly Results Devastation for AZ as Imfinzi fails AZ hands half of Lynparza to Roche, AZ, Eli Lilly, Celgene, Amgen PFS endpoint (p5) Merck & Co (p8) and BMS (p6, 11, 18-21) IN THIS ISSUE

from the editor [email protected]

Announcements from twin engines of UK pharma, survival endpoint (page 5), while the deal the company GlaxoSmithKline and AstraZeneca were the hottest signed with Merck & Co for Lynparza and selumetinib is news affecting the industry last week. to be viewed with caution. It brings in a healthy chunk GSK saw its share price dip by 4.6% by the end of the of up-front money and the potential for sizeable mile- week after new CEO Emma Walmsley put her stamp on stones, but dilutes the company’s future profits and was the company by announcing a major shake-up of the seen by some as an indication that AZ was losing confi- pharma business on Wednesday (see cover story). With dence in its immuno-oncology assets (p8). multiple cuts and a strategic review of the rare diseases AstraZeneca’s stock plummeted by almost 17% in portfolio envisaged, the aftershocks will resound for reaction to Thursday’s MYSTIC revelation. Still, inves- some time. Still, there could be opportunities for others tors came out in support of CEO Pascal Soriot. Con- as assets go looking for new homes. trary to recent rumors, he appears to be staying put For AstraZeneca, any positives – healthy second-quar- and is standing by his long-term expectations for the ter figures (p6), encouraging data on Tagrisso in first- company, Imfinzi disappointment notwithstanding line EGFR mutant non-small cell lung cancer – were (p4). The stock bounced back to end the week 12.4% effectively obliterated by the news that the much-antic- lower than it had been before AZ dropped its cluster ipated MYSTIC trial had missed on its progression-free bomb of news.

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

2 | Scrip intelligence | 4 August 2017 © Informa UK Ltd 2017 Second Remicade 9 Biosimilar

Keytruda Gets PD-1 Possibilities In 20 Benefit Of Doubt 10 Cervical Cancer 16

exclusive online content inside: COVER / Walmsley Shakes Up GSK; Cuts 30 Drug Programs Gilead Raises HCV Guidance Slightly, 4 Soriot Stands By His Post-Pfizer Sales Pledge For AZ Still Mum On M&A http://bit.ly/2vYdAZZ 5 MYSTIC Misses: Devastation For AstraZeneca As Imfinzi Fails Gilead Sciences Inc. still didn’t have anything concrete to PFS Endpoint In NSCLC say about M&A strategy during its second quarter earnings 6 AstraZeneca 2Q: Soriot’s In It For The Long Haul call on July 26, but it surprised market analysts anyway by increasing 2017 sales guidance for its hepatitis C virus (HCV) 8 A Whopper Of A Deal: AZ Hands Half Of Lynparza To Merck drugs just a few months after slashing expectations for its sofosbuvir-driven portfolio. 9 Merck’s Second-To-Market Renflexis Biosimilar Priced Below The First

Almirall’s “Perfect Storm”: How Will It Recover? 10 Merck’s Keytruda Gets Benefit Of Doubt, Despite Failing in Head & Neck http://bit.ly/2wejfu9 Spain’s Almirall SA revealed on July 24 that a further part of its 11 Lilly Hopes To Revitalize Its Cancer Brand With ‘Foundational’ business, the aesthetic company ThermiGen, has had a “slow Agents start to the year,” adding to what CEO Eduardo Sanchiz has already called a “perfect storm” of adverse business issues during 12 Celgene Eases Angst Over Otezla the first half of this year. 13 Lilly/Nektar’s ‘Stimulating’ IL-2 Drug 14 Biogen’s Neuroscience Strategy Includes De-Risking The Are Theravance And Mylan’s US COPD Chances Bigger Pipeline Than First Thought? http://bit.ly/2uQPoZx 15 J&J Prepares For US Sirukumab Launch After Regaining Partners Mylan NV and Theravance Biopharma Inc. say they Rights From GSK will submit their nebulized once-daily LAMA respiratory drug 16 PD-1 Data Emerge In Cervical Cancer revefenacin for regulatory approval after receiving good Phase III safety and tolerability data for the long-acting muscarinic 17 Roche Lifts Outlook, Spotlights Perjeta To Drive Growth antagonist (LAMA) in treating chronic obstructive pulmonary 18 Amgen Beats Consensus, Raises Earnings Guidance, But Is It disease (COPD). Sustainable? 19 Bayer And Morphosys Brush Off ADC Mesothelioma Failure Dong-A Faces Price Hit As Korea Ups Fight Against Illegal Rebates 20 Post-MYSTIC, Bristol Renews CTLA-4 Vows, But Is http://bit.ly/2vj4jy2 “Not Wedded” In Lung Cancer In its ongoing clamp down against illegal rebate activities in 21 J&J’s Symtuza Will Debut In Europe On Cramped HIV Market the domestic pharmaceutical industry, South Korea cuts prices of Dong-A ST’s drugs. This follows recent punitive measures 22 Pipeline Watch against Novartis’ Korean subsidiary. 23 Will Mitsubishi’s High Offer Price For CNS Target NeuroDerm Deter Others? Policy Prescriptions: User Fees, Biosimilars, Brexit 23 Appointments http://bit.ly/2tR3M2n A round up of recent regulatory news and trends reported by sister publication, the Pink Sheet, including the struggle to clear the FDA user fee reauthorization bill, the regulatory pathway for Mylan’s biosimilar trastuzumab and Amgen’s biosimilar bevacizumab, and Brexit planning by the European @PharmaScrip /scripintelligence Medicines Agency.

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scrip.pharmamedtechbi.com 4 August 2017 | Scrip intelligence | 3 EXECUTIVE INTERVIEW

Soriot Stands By His Post-Pfizer Sales Pledge For AZ ELEANOR MALONE [email protected]

ust one day after the revelation that AstraZeneca PLC’s PD-L1 In the words of Bohen, “if you don’t have failures, you’re not taking inhibitor Imfinzi (durvalumab) as monotherapy and combined enough risks.” Both executives underlined that for MYSTIC the end Jwith its CTLA-4 inhibitor tremelimumab had failed to meet the game has always been overall survival as opposed to progression- progression-free survival endpoints in the much-anticipated MYSTIC free survival. “With MYSTIC […] we tried to see whether with the PFS trial in first-line treatment of stage IV non-small cell lung cancer, CEO endpoint, that reached earlier than OS, we could get to market faster,” Pascal Soriot was standing by the ambitious sales growth targets he said Soriot. “If [PFS] had been positive we would have been able to set for the company in 2014. launch earlier – so it was a risk we took.” As he successfully defended AstraZeneca from a $119bn takeover Indeed, that feverish race to market has claimed other casualties bid by Pfizer Inc. in May 2014, he had said the UK company would among AZ’s rivals, most notably including BMS in first-line NSCLC. achieve standalone sales of $45bn in 2023, driven by its diabetes “But,” said Soriot, “the reality is, we believed in OS and we still be- and respiratory franchises and growth from the antiplatelet therapy lieve in it, and the investors I’ve talked to are basically in the same Brilinta (ticagrelor), immuno-oncology sales and the PARP inhibitor place. They see the totality of the picture. Of course they are disap- Lynparza (olaparib). Now, despite pipeline setbacks and scaled down pointed, like we are, that PFS didn’t read out.” In fact, in a July 27 blog forecasts for Brilinta, he has claimed that “at this point there is no post, fund manager Neil Woodford wrote that the MYSTIC news “is reason to think we can’t achieve it”, although with the subsequent not evidence of the failure of the drug, nor of the strategy, nor indeed decline in the value of the dollar, “$45bn is a bit more than $40bn at of the rationale for my investment in AstraZeneca,” adding that there current exchange rates.” was “more than enough evidence to show its chief executive’s strat- Meanwhile, the CEO argued that the market value of the compa- egy is working” and that “very little of what I believe the company will ny ought to reflect its profitability, “and some of the products we’re achieve is reflected in today’s share price”. launching are really profitable.” However, he would not give mid- term guidance on profitability. HERE TO STAY? Soriot, speaking with AstraZeneca’s chief medical officer Sean Bo- Woodford’s faith in Soriot’s leadership chimes with the CEO’s pro- hen to a handful of broadsheet journalists and Scrip in the aftermath fessed attachment to the role. “You don’t commit five years of your of the company’s 15% share price plunge on July 27, sought to mini- life to try and do something and give up as you think you’re almost mize the MYSTIC bombshell and emphasize the unexpected posi- getting there,” said Soriot, while refusing to comment on rumors that tives and future opportunities for AZ. he may have spoken to Teva Pharmaceutical Industries Ltd. about the CEO vacancy there. “I can only say that it would break my heart to TAGRISSO: MULTI-BILLION DOLLAR PRODUCT not see the opening of this Cambridge building; that’s an important The executives played up the opportunity for Imfinzi in Stage III lung part of this journey,” he added. cancer (on the back of the PACIFIC trial data), and argued that the The relocation of AZ’s headquarters and UK R&D hub to Cambridge FLAURA trial data on Tagrisso (osimertinib) in first-line EGFR muta- is currently delayed by 3-5 months, with the opening expected in the tion-positive NSCLC, also announced on July 27, had been under-ap- second half of 2018. preciated. (Also see “AstraZeneca’s Imfinzi Steals March Into Untapped Asked when he would consider his mission accomplished, Soriot said IO Lung Cancer Territory” Scrip, 12 May, 2017.) it would be a couple of years away at least, “when we’ve launched all “Two years ago, people were saying Tagrisso is behind the competi- these products and they’re starting to grow and we can show the en- tion; it’s not such a great product anyway. Now the competition has gine is renewing the pipeline, and we’re out of this transition phase of disappeared because of side effects and there’s no competition for losing patent protection on key products and reinvesting in the future.” three-four years,” declared the CEO. “In the meantime, we’ve shown Even if neither he nor his investors currently wish him to leave that Tagrisso penetrates the blood brain barrier – and 20-25% of pa- AstraZeneca, whether he will still be there in six years’ time to oversee tients in first line lung cancer with EGFR mutation have brain metasta- the fulfillment of his post-Pfizer growth pledge is another matter, and ses. Tagrisso is as effective on those as it is on the lung disease, and it’s one which will hinge not solely on the fact that, as Soriot revealed, “at going to be a multi-billion dollar product, and the data we announced some point I will want to go and see my grandson in Australia and yesterday will be presented soon, and they are really great data.” retire there.” Other forthcoming growth opportunities included the anticipated Not that it will rest just on the MYSTIC PFS read-out, nor even on approvals of acalabrutinib in blood cancer and benralizumab in se- MYSTIC OS data, either. From respiratory to diabetes, kidney disease vere, uncontrolled asthma – which Soriot described as “best in class” and across the gamut of oncology, AstraZeneca can still count on a – as well as roxadustat, the hypoxia-inducible factor prolyl hydroxy- considerable number of impending trial results, approval decisions lase inhibitor for anemia in kidney disease which AZ in-licensed for and existing product expansion possibilities. However, with every the US and China from FibroGen Inc. and for which Soriot believes late-stage trial miss – and in recent times these have included the the market prospects are “potentially enormous.” Soriot also believes likes of tralokinumab in asthma, MEK inhibitor selumetinib in NSCLC, SGLT2 inhibitor Farxiga (dapagliflozin) has a rosy future. Brilinta in important additional indications and now MYSTIC – the AstraZeneca currently invests a little over 50% of its R&D spend in pressure mounts on Soriot to convert the remaining opportunity oncology. into extraordinary results. Published online 30 July 2017

4 | Scrip intelligence | 4 August 2017 © Informa UK Ltd 2017 HEADLINE NEWS

MYSTIC Misses: Devastation For AstraZeneca As Imfinzi Fails PFS Endpoint In NSCLC LUCIE ELLIS [email protected]

straZeneca PLC’s PD-L1 inhibitor, 2Q Numbers At A Glance positively at a later date,” Deutsche Bank Imfinzi (durvalumab), a drug ex- Total revenue: $5.1bn analysts said, adding that AstraZeneca can Apected to act as the big pharma’s Core EPS: $0.87 still carve out a section of the PD-L1 market backbone drug across its cancer immuno- Tagrisso sales: $232m based on Imfinzi in locally advanced lung therapy portfolio, has failed to meet primary cancer and other settings. Imfinzi sales (launched in May 2017): $1m progression free survival (PFS) endpoints in Stage IV NSCLC aside, Imfinzi has trials on- Oncology sales: $993m the Phase III MYSTIC trial in non-small cell going in several other indications including Respiratory sales: $1.1bn lung cancer. head and neck, small cell lung, breast and Cardiovascular and metabolic sales: pancreatic cancer. In the Phase III study Imfinzi, a program $1.8bn death-ligand 1 inhibitor, in combination Financial guidance for full year 2017 reiter- with tremelimumab failed to improve PFS ated; total revenue will see a low to mid NSCLC MARKET SHARE compared to platinum-based standard of single-digit percentage decline, while EPS AT STAKE care chemotherapy in previously untreated will experience a low to mid-teens percent- Before MYSTIC’s PFS reveal, Biomedtracker patients with metastatic NSCLC – marking a age decline. analysts had granted Imfinzi, which is al- huge setback for AstraZeneca in this space. ready on the market for the treatment of AstraZeneca also announced that mono- Imfinzi data coming forward from other bladder cancer, a 42% likelihood of approval therapy Imfinzi, although not formally trials, such as the Phase III PACIFIC study rating for NSCLC – 7% above the average. tested, would not have met a pre-specified in Stage III NSCLC that read out in May this Data from MYSTIC has been long-await- threshold of PFS benefit over standard of year. (Also see “AstraZeneca’s Imfinzi Steals ed by the market because a positive result care in this disease setting. March Into Untapped IO Lung Cancer Terri- would see AstraZeneca compete with its The UK-based company’s share price tory” Scrip, 12 May, 2017.) biggest immuno-oncology rivals in a large (London Stock Exchange) plummeted more Jefferies analysts did not share Bohen’s lung cancer market. PD-1/L1 drugs from the than 16% in the morning of July 27 on the sentiment in a July 27 note, in which they likes of Bristol-Myers Squibb Co., Roche news these crucial endpoints were missed. said “the story is as good as over” for Imfinzi and Merck & Co. Inc. are already on the The MYSTIC trial will continue to assess in first-line NSCLC. market in a NSCLC setting and AstraZeneca’s overall survival (OS) endpoints for Imfinzi “We are skeptical of MYSTIC’s ability to product is playing catch up. monotherapy and the Imfinzi plus treme- show an OS benefit for both mono and Of the five marketed PD-1/L1 inhibitors, limumab combination. Final OS data are combo following the PFS fails,” analysts only Imfinzi andMerck KGAA/Pfizer Inc.’s expected during the first half of 2018, but said. Jefferies had modeled for $3.3bn Bavencio (avelumab) are yet to be approved the prognosis isn’t good. Tremelimumab is in peak sales for Imfinzi in metastatic in NSCLC. Bavencio, which has a 40% likeli- AstraZeneca’s investigational human mono- NSCLC before the news of MYSTIC’s PFS hood of approval rating in NSCLC, is in Phase clonal antibody that targets the activity of failure – $500m sales as a monotherapy III with data expected in the first-line treat- cytotoxic T-lymphocyte-associated protein and the rest from the combination with ment setting in 2019. 4 (CTLA-4). tremelimumab. BMS’s Opdivo (nivolumab) was the first Sean Bohen, AstraZeneca’s executive VP Leerink analysts were also down on Im- PD-1 inhibitor to win approval in second- of global medicines development and chief finzi’s outlook in first-line NSCLC: “We see line NSCLC, securing an FDA nod in March medical officer, said the initial results from commercial success of this combination as 2015 – but the drug suffered a setback in the first-line setting in Oct. 2016. (Also see the Phase III study are “disappointing.” How- severely limited even if a small benefit on “’Total Disaster’ In First-Line Lung Cancer For ever, he tried to remain positive, claiming survival is ultimately realized,” analysts said BMS’s Opdivo” Scrip, 10 Oct, 2016.) that the MYSTIC study is designed to mea- in a July 27 note. BMS has several combination trials ongo- sure OS not PFS. “We look forward to evalu- Meanwhile, a Deutsche Bank analysis of the impact of MYSTIC on AstraZeneca’s ing for Opdivo in NSCLC, and many clinical ating the remaining primary endpoints of long-term immuno-oncology portfolio was studies in other cancers. overall survival for both mono- and combi- less dramatic. In a July 27 note, analysts said Meanwhile, Merck’s Keytruda (pembroli- nation therapy,” he said. the MYSTIC miss on PFS was a “major disap- zumab), approved for second-line NSCLC in AstraZeneca’s CEO Pascal Soriot simply pointment,” however they believe AstraZen- Oct. 2015, is leading the PD-1/L1 pack in the said during the company’s 2Q analyst and eca “can still return to solid EPS growth even first-line treatment space. In May 2017, Mer- investor call on July 27 that the market without a positive outcome of MYSTIC.” ck’s anti-PD-1 therapy, in combination with must wait until the first half of 2018 “to get “We remind investors that it remains per- pemetrexed and carboplatin (a commonly the full picture” of the MYSTIC study. He fectly feasible that OS data could still report added that the company is pleased with CONTINUED ON PAGE 6 scrip.pharmamedtechbi.com 4 August 2017 | Scrip intelligence | 5 QUARTERLY RESULTS

CONTINUED FROM PAGE 5 used chemotherapy regimen) won condi- tional approval in the US for the first-line treat- AstraZeneca 2Q: Soriot’s In It For ment of metastatic non-squamous NSCLC, irrespective of PD-1 expression. The Long Haul Roche’s Tecentriq (atezolizumab) was ap- LUCIE ELLIS [email protected] proved in second-line NSCLC in Oct. 2016; the Swiss pharma plans to file for US/EU espite the surprising failure of As- a $3m net loss a year earlier, when the com- approval of Tecentriq for the first-line treat- traZeneca PLC’s key cancer im- pany took a restructuring charge related to ment of squamous and non-squamous Dmunotherapy agent, Imfinzi (dur- job cuts. Total revenues came in at $5.1bn NSCLC in 2019. valumab), in first-line non-small cell lung for 2Q 2017 – bringing the figure for the first cancer – news that slashed more than half of the year to $10.5bn. EPS for the quar- POSITIVE NSCLC NEWS 15% off the company’s share price on ter was $0.87. The same day AstraZeneca reported a set- July 27 – CEO Pascal Soriot has declared Oncology sales in 2Q 2017 were $993m, back for Imfinzi in NSCLC, the company his intentions to remain at the company, while respiratory sales came in at $1.1bn, also announced positive headline data finally settling qualms about his possible and the group’s cardiovascular and meta- from its Phase III FLAURA trial for Tagrisso departure. bolic drugs netted $1.8bn. (osimertinib) in the same therapy area. During the company’s second quarter Based on the company’s 2Q performance In the study, patients with locally-ad- analyst and investor conference call, So- and the news of MYSTIC’s miss in first-line vanced or metastatic epidermal growth riot said he was “proud of being CEO” of NSCLC, Jefferies analysts said the company factor receptor mutation-positive (EGFRm) AstraZeneca, adding that he is committed does not look as well protected from poten- NSCLC treated with Tagrisso experienced to “seeing through” his journey at the UK- tial takeover bids. significant progression-free survival (PFS) based big pharma. “The dividend may now look less safe and benefit compared to patients receiving cur- The rumor mill has been whirring this we expect some investors will start to ques- rent first-line standard of care treatment (er- month after Israel-based Calcalist, a finan- tion its long-term sustainability, despite pri- lotinib or gefitinib). cial news website, reported on July 12 or reassurances from management,” analysts AstraZeneca will begin talks with regu- that Soriot had met with Teva Pharma- said in a July 27 note. “We would expect the latory authorities on the back of these ceutical Industries Ltd.’s search com- stock to find some support as a potential data and plans to present the results at mittee and its chair, and expressed his in- consolidation target, once the negative im- a forthcoming medical meeting. Tagrisso, terest to serve as the generics company’s pact of MYSTIC has been priced in,” Jefferies which is already approved for NSCLC, is next CEO. The news sent AstraZeneca’s analysts added. likely to become the new standard of share price tumbling and spurred head- AstraZeneca fended off a takeover bid by care therapy. lines across the globe that the company’s US big pharma Pfizer Inc. in 2014 on the Bohen called the Phase III data for Tagrisso CEO was jumping ship. basis of its strong, independent pipeline. “exciting” and said the drug could soon pro- On July 16, Soriot responded to the ru- vide doctors with a new first-line treatment mors he was leaving AstraZeneca for a rival UPCOMING DATA CATALYSTS option to improve outcomes in this NSCLC drug maker via an internal company memo, Analysts also expect the poor PFS results population. Approximately 10-15% of pa- reported first by Bloomberg on July 20, but from the MYSTIC study will dampen Astra- tients in the US and Europe, and 30-40% of his vague remarks still left some speculating Zeneca’s remaining readouts for its Imfinzi patients in Asia have EGFRm NSCLC. over his future as CEO. plus tremelimumab combination. There are Deutsche Bank analysts said a first-line Analysts had also ventured at the time a number of studies due to read out over EGFRm lung cancer indication could “ma- that Soriot’s potential departure could be the next 12 to 18 months. terially expand Tagrisso’s commercial po- linked to the likelihood of a poor outcome • Overall survival data from the ARCTIC tential, increasing peak sales to approxi- from the Phase III MYSTIC study – it seems trial in second-line PD-L1 low/negative mately $3bn.” they were half right. NSCLC patients is expected in the sec- Tagrisso is a third-generation EGFR tyro- Now Soriot has used the company’s 2Q ond half of 2017; sine kinase inhibitor (TKI) designed to inhibit earnings presentation to further clarify that • PFS data from the KESTREL study in first- both EGFR sensitizing and EGFR T790M re- he has no plans to leave the business soon. line squamous cell carcinoma of the head sistance mutations. However, the MYSTIC trial of Imfinzi (a PD-L1 and neck (SCCHN) is also expected for the The primary endpoint of the FLAURA inhibitor) plus tremelimumab (an anti-CT- end of the year; trial, which included 556 patients across 30 LA-4) failed to show favorable progression • Meanwhile, in 2018 AstraZeneca will re- countries, was PFS; secondary endpoints free survival benefit compared to current port data from the EAGLE trial in second- include overall survival, objective response standard of care. line SCCHN, PFS results from the DANUBE rate, duration of response, disease control study in first-line urothelial bladder can- rate, safety and measures of health-related IS A TAKEOVER BACK ON TABLE? cer and OS data from the NEPTUNE and quality of life. In the second quarter of 2017, AstraZeneca MYSTIC trials in first-line NSCLC. Published online 27 July 2017 posted net profits of $477m, compared with Published online 27 July 2017

6 | Scrip intelligence | 4 August 2017 © Informa UK Ltd 2017 QUARTERLY RESULTS – GLAXOSMITHKLINE

CONTINUED FROM COVER 2Q Numbers At A Glance nstein analyst are wary of this approach, when it comes to translating R&D drug Group sales: £7.3bn they noted that “prior attempts to divest candidates into commercial successes; Operating profit: £2.08bn core brands by big pharma has met with she also noted that development time- EPS: 27.2p mixed results.” lines at GSK are too slow and R&D in Pharmaceutical sales: £4.36bn Phase II is taking the company much lon- (cons: £4.31bn) GIVING A DAMN ABOUT ger than its peers. Vaccines sales: £1.11bn (cons: £1.08bn) REPUTATION Walmsley added that recently appointed Under the third corporate heading of “trust,” Consumer health sales: £1.85bn global head of pharmaceuticals Luke Miels (cons: £1.89bn) Walmsley made a point of highlighting that would be leading the charge to improve Of the major Pharma products Triumeq reputation is important to GSK. She said governance of GSK’s pipeline decision mak- and Tivicay both beat by 8% and 5%, the company is continuing to develop its ing. She said Miels’ experience would be “in- respectively, delivering a 4% beat for GSK’s healthcare practitioner engagement model valuable.” The incoming pharma chief, who ViiV Healthcare business. to make sure it is a “competitive and trusted” joins the company from AstraZeneca PLC, company. will start his new role in September. (Also limited opportunities. As part of this strategy, Under the leadership of Walmsley’s pre- see “GSK Management Shake Up Ahead Of the company has dumped its sirukumab de- decessor Sir Andrew Witty, GSK was fined New CEO Sees Hussain Out, AZ’s Miels In” velopment and commercialization partner a record sum of $486m in September 2014 Scrip, 19 Jan, 2017.) Janssen Pharmaceutical Cos. (a Johnson after it was officially found guilty of bribery Miels will lead a “deep review” into effi- & Johnson company) (See story on p15.). in China by the Changsha Intermediate ciency and effectiveness of drug develop- As well as terminating its collaboration for People’s Court in Hunan Province. (Also see ment at GSK and is expected to appoint a immunology drug sirukumab, GSK will pro- “Witty’s Bonus Slashed As GSK Recovers From new leadership team within the pharma gressively withdraw its support for its own China Scandal” Scrip, 8 Mar, 2015.) unit, Walmsley said. She added that the marketed type 2 diabetes drug Tanzeum The inclusion of “trust” as a core prin- company’s aim is to “develop the next wave (albiglutide). ciple and a mention of the company’s of innovation.” A BLA for sirukumab has recently been ongoing changes to how it communi- filed in the US for rheumatoid arthritis and cates with doctors were subtle nods from GETTING UP TO SPEED Janssen has Phase III trials ongoing in giant Walmsley, suggesting she’ll be running a GSK’s CEO also noted that the company cell arteritis and inflammatory disorders and tighter ship. will focus more on technology investment. Phase II studies for asthma and major de- She said GSK must be agile and investors pressive disease. Janssen and GSK entered a LOOKING AHEAD TO 2020 should expect material shifts in the way co-development and co-commercialization GSK’s forthcoming target, which is spurring the company uses data and analytics. As an license agreement for sirukumab in its RA current cost-cutting initiatives, is to deliver industry, Walmsley said pharma companies indication in 2011. an additional £1bn in annual cost savings need to “reassess who our competitors and GSK’s decision to drop sirukumab is surpris- by 2020. These cost savings will be used to partners are.” ing because less than a year ago, the com- fund new product launches, R&D invest- To drive a greater use of new digital tech- pany highlighted the anti-interleukin-6 (IL-6) ments and to help mitigate pricing pressure nologies GSK has appointed Karenann Ter- antibody as potentially its first new product on margins, the company noted. rell as its new chief digital and technology in immuno-inflammation beyond Benlysta During its second quarter earnings, GSK officer – effective from Sept. 4, 2017. Terrell (belimumab). GSK’s chief immunology officer reiterated the company’s outlook for sales will be responsible for developing the com- Paul-Peter Tak told Scrip in September 2016 and earnings performance out to 2020; the pany’s digital, data and analytics strategy. that he saw sirukumab as an anchor for GSK’s company expects sales to grow at a low- She was previously chief information offi- emerging immuno-inflammation pipeline. to-mid single digit percentage compound cer for Walmart, where she focused on the Meanwhile, Tanzeum was only ap- annual growth rate and adjusted EPS to company’s use of data, analytics and digital proved in the US in 2014 and had been grow at a mid-to-high single digit percent- engagement with customers. Before this forecast to reach peak annual sales of age CAGR between 2016 and 2020. she was chief information officer atBaxter $1.8bn by 2023. The future of ongoing GSK has lowered its guidance for the full International Inc. clinical studies for the drug in congestive year 2017, the drug major now expects to heart failure and type I diabetes is uncer- grow annual adjusted EPS at constant cur- IT’S NOT YOU, IT’S ME tain now that GSK is withdrawing financial rency by 3% to 5% over the full year 2017, To address its second corporate priority of backing for the product. lowering its target from the original aim to “performance,” GSK will move capital and GSK will also seek to divest 130 non-core grow earnings by 5% to 7%. resources away from markets that only offer brands, totaling approximately £500m. Ber- Published online 26 July 2017

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scrip.pharmamedtechbi.com 4 August 2017 | Scrip intelligence | 7 DEAL

A Whopper Of A Deal: AZ Hands Half Of Lynparza To Merck JESSICA MERRILL [email protected]

straZeneca PLC agreed to partner two important oncology Deutsche Bank analyst Richard Parkes commented in a same day drugs with Merck & Co. Inc. after its PD-1 inhibitor Imfinzi note, “On the positive side, the deal will allow AstraZeneca to acceler- A(durvalumab) disappointed in a key trial, raising questions ate and expand development of Lynparza to an extent that would about whether the company ceded long-term earnings for a near- not have been possible with the restraints of its R&D budget.” term win. But, he added, “AstraZeneca is effectively giving away 50% of the The UK drug maker announced the sweeping oncology deal on future profits of Lynparza (2022 consensus total sales $1.1bn), and July 27, agreeing to share development and commercialization of bears will argue this has been done simply to prop up near-term the marketed ADP ribose polymerase (PARP) inhibitor Lynparza earnings.” (olaparib) and the investigational MEK inhibitor selumetinib with Based on $1.1bn sales estimates for Lynparza, net present value Merck. In exchange, Merck agreed to pay $1.6bn up front and a total translates to around $3.8bn, he pointed out. “Thus, AstraZeneca has of $8.5bn potentially including milestones. crystalized close to 50% of this value up front,” he said. “The primary purpose of this collaboration is to accelerate and Leerink analyst Seamus Fernandez was more critical of the deal, expand the potential of Lynparza and to make Lynparza the PARP saying AstraZeneca appears to be admitting defeat in immuno-on- inhibitor of choice,” AstraZeneca CEO Pascal Soriot said during the cology. “The fact that AstraZeneca sold off 50% of the opportunity for company’s second quarter sales and earnings call the same day. Lynparza, while economically feasible risk management, raises near- It was a big news day for AstraZeneca, and the deal announce- term concerns about the sustainability of the company’s cash flow,” ment was overshadowed by the company’s release of the initial re- he said in a research note. sults from the much-anticipated MYSTIC trial. The study, which has implications beyond AstraZeneca and across the PD-1/L1 field, was a PD-1/L1 COMBO REMAINS INDEPENDENT blow to AstraZeneca, which needed a win to catapult it from a come- Under the agreement, AstraZeneca and Merck will develop and from-behind position into a solid player in the multi-billion-dollar commercialize Lynparza jointly, both as monotherapy and in immuno-oncology space. combination with other medicines. The firms will independently Imfinzi was approved for bladder cancer in May, but AstraZeneca develop and commercialize Lynparza in combination with their has been hoping to jump into the commercially lucrative lung can- respective PD-L1/PD-1 medicines, Imfinzi and Merck’s Keytruda cer market with an efficacious combination. (pembrolizumab). The companies will jointly develop and com- MYSTIC tested Imfinzi as monotherapy and in combination with mercialize selumetinib, which is being tested in multiple indica- the CTLA-4 inhibitor tremelimumab versus chemotherapy in non- tions including thyroid cancer. small cell lung cancer patients. The combination did not improve Selumetinib has run up against its own setbacks, including a disap- progression-free survival, though the study is continuing, with full re- pointing Phase III trial in combination with chemotherapy in second- sults expected in 2018, including overall survival data. AstraZeneca’s line KRAS mutation-positive advanced or metastatic NSCLC. stock fell 15% to open at $28.77. The deal gives Merck a PARP inhibitor to combine with Keytruda, a combination that has shown promise in early clinical trials. How- HANDING HALF THE PROFITS TO MERCK To take the heat off, AstraZeneca simultaneously announced the ever, it’s not an outright win for Merck either, seeing as the com- partnership with Merck, agreeing to sacrifice full ownership of Lyn- pany out-licensed its own PARP inhibitor to Tesaro Inc. in 2012 for parza for more resources to invest behind a broad development pro- significantly less. gram, with an eye toward leading in the competitive space. Lynparza Tesaro paid just $7m up front, and agreed to pay $57m in develop- is currently approved for a niche indication, BRCA-mutated ovarian ment and regulatory milestones for the first indication, up to $29m cancer, but is being studied in 14 indications across several tumor for each successive indication and up to $87.5m in one-time sales types including breast, prostate and pancreatic cancer. milestones. Tesaro’s drug, Zejula (niraparib) was approved by the US Lynparza generated sales of $116m in the first half of 2017, repre- FDA in March for recurrent ovarian cancer, with a broader label than senting 18% growth. And the company has its sights set on securing Lynparza, for recurrent ovarian cancer regardless of mutation status. approval in BRCA mutated breast cancer following positive Phase III Soriot insisted the deal does not reflect diminished confidence in data reported earlier this year. AstraZeneca’s Imfinzi. “We have total confidence in durvalumab, but “We actually partner products where we believe we can create we are also realistic,” he said. “Durvalumab will not get 100% share of more value with our partner, and here, there is a clear benefit in part- the immuno-oncology market.” nering with Merck,” Soriot said. Merck agreed to pay AstraZeneca $1.6bn up front, $750m for cer- Analyst reaction to the news wasn’t exactly enthusiastic. The deal tain license options and up to $6.15bn in future regulatory and sales will give AstraZeneca a development advantage in the competi- milestones. AstraZeneca will book product sales and pay gross prof- tive PARP space, but also hands over half the profits of a near-term its due to Merck. growth driver to a rival. Published online 27 July 2017

8 | Scrip intelligence | 4 August 2017 © Informa UK Ltd 2017 BIOSIMILAR PRICING

Merck’s Second-To-Market Renflexis Biosimilar Priced Below The First JESSICA MERRILL [email protected]

erck & Co. Inc. has launched Ren- flexis (infliximab-abda), the com- Mpany announced on July 24, marking the first time two biosimilars will compete against a brand drug in the US. Renflexis is the second biosimilar version of Johnson & Johnson’s blockbuster anti-TNF Remicade (infliximab) to reach the US market behind Pfizer Inc.’s Inflectra(infliximab-dyyb). Merck appears to be competing aggres- sively on price, which will be welcome news to payers. The company set the wholesale acquisition cost of Renflexis at $753.39, reflecting a 35% discount to the list price of Remicade. The WAC is considerably lower than the one set by Pfizer for Inflectra, which Shutterstock: Lightspring Shutterstock: launched in November 2016 at a 15% discount to Remicade. (Also see “Pfizer Will Sup- process patents for Remicade. “We will port Inflectra Launch With Dedicated Sales Renflexis is the first continue to defend our intellectual prop- Force” Scrip, 14 Nov, 2016.) But it’s still unclear erty rights relating to our innovative med- how the drugs stack up to one another on biosimilar to launch under icines,” J&J said. price after rebates and discounts. a multi-product agreement The launch of a second biosimilar will The WAC does not reflect the impact put more pressure on Remicade, which is of rebates and discounts, and J&J previ- between Merck and beginning to feel the weight of its maturi- ously said Remicade’s price is about 30% Samsung signed in 2013 ty. Sales of J&J’s blockbuster brand dipped lower than the WAC when factoring in 14% to $1.53bn worldwide in the second rebates and discounts. Merck would not quarter, but only a small fraction of the comment further on what if any rebates decline was attributed to the launch of it will apply to Renflexis but did say the Merck and Samsung signed in 2013. (Also biosimilar competition in the US. Manage- WAC price was exclusive of any additional see “Merck Partners With Korea’s Samsung ment insisted during the second-quarter rebates and discounts. Bioepis On Multiple Biosimilar Targets” Scrip, earnings call July 18 that the initial launch Renflexis, developed bySamsung Bioepis 20 Feb, 2013.) Under the collaboration, Merck of Inflectra has had a more moderate- Co. Ltd., was approved by the FDA in April for is in charge of commercialization, while Sam- than-expected impact on Remicade. (Also all seven of the indications included on Remi- sung is responsible for development, regula- see “Remicade: Biosimilars And Pricing Pres- cade’s labeling (Also see “Samsung’s Renflexis: tory approval and manufacturing. Merck sure Wear On J&J’s Blockbuster Brand” Scrip, Second US Biosimilar To Janssen’s Remicade, dove headlong into the biosimilar space in 18 Jul, 2017.) With A Few Firsts” Scrip, 21 Apr, 2017.) 2008, envisioning the launch of six follow-on When chief financial officer Dominic At the time, Merck would not say when it biologics between 2012 to 2017, but later Caruso was asked about the potential im- expected to launch the product. However, pulled back on the initiative and reset its am- pact of a second biosimilar, if launched, he the rollout comes six weeks after the US Su- bitious plans with a partner instead. (Also see said he remained confident that Remicade preme Court ruled that biosimilar sponsors “Merck Announces Major FOB Initiative With share erosion would be minimal in 2017, need not wait until the FDA approval before Its New Business Unit” Scrip, 9 Dec, 2008.) given that managed care contracts are giving innovators 180-day notice of com- J&J said it considers the launch to be “at largely in place. mercial launch. (Also see “Biosimilar Launch- risk,” meaning that it believes it violates the Nonetheless, as the competitive dynam- es Depend Mostly On Patents After Supreme company’s patent protection for Remicade. ics intensify, Remicade makes an interesting Court Ruling” Scrip, 13 Jun, 2017.) The company has filed a lawsuit against test case to see how the US biosimilar mar- Renflexis is the first biosimilar to launch Samsung to investigate whether the bio- ket may unfold. under a multi-product agreement between similar infringes on the manufacturing Published online 24 July 2017

scrip.pharmamedtechbi.com 4 August 2017 | Scrip intelligence | 9 CLINICAL TRIALS

Merck’s Keytruda Gets Benefit Of Doubt, Despite Failing in Head & Neck EMILY HAYES [email protected]

erck & Co. Inc.’s PD-1 inhibitor rise, driving up overall incidence per year Roche announced in May that its PD-L1 Keytruda (pembrolizumab) has in the US from 39,700 in 2005 to 59,500 in inhibitor Tecentriq (atezolizumab) failed to Mfailed to show a survival benefit 2015. Incidence has been rising, but stan- show an overall survival (OS) benefit in the in the KEYNOTE-040 study of head and neck dard therapies have failed a large number confirmatory IMvigor 211 study of second- cancer, which was meant to confirm an ac- of patients. line bladder cancer, following accelerated celerated approval, but the company does Morningstar estimates sales of $1bn approval for this indication in May 2016. not foresee a labeling change. for this indication in 2021, out of a total of (Also see “Could Tecentriq’s Bladder Cancer Set- back Be A Class Effect?” Scrip, 12 May, 2017.) Bristol’s Opdivo failed to show a benefit for second-line brain cancer in the Check- Mate 143 study of glioblastoma. (Also see “Immuno-Oncology Outlook: Looking For Brain Cancer Options” Scrip, 3 Jul, 2017.) And, more importantly, Opdivo also failed to show an OS benefit in the CheckMate 026 first-line non-small cell lung cancer study. (Also see “Was PD-L1 Test To Blame For Failure Of Bristol’s Opdivo In ‘026 Trial?” Pink Sheet, 22 Jun, 2017.) In contrast Keytruda did show a survival benefit in first-line lung cancer and is approved for this use in combination with chemotherapy. Bernstein analyst Tim Anderson said in a Shutterstock: sciencepics Shutterstock: July 24 note that the news about Merck’s Keytruda failure in the Phase III head and Merck said on July 24 that median overall $28bn. (Also see “Immuno-Oncology Out- neck study is “not as bad as it might seem.” survival (OS) for Keytruda in the study of re- look: Getting To The Root Of Head And Neck The FDA is likely taking no action in terms current or metastatic head and neck cancer Cancer” Scrip, 21 Jul, 2017.) of changing the label because the survival was better than investigator’s choice of che- Bristol-Myers Squibb Co. won full ap- benefit was close to reaching statistical motherapy, with an 18% reduction in risk proval for its competing PD-1 inhibitor significance. “The agency might also be in- for death in the KEYNOTE-040 study of 495 Opdivo (nivolumab) in October 2016 for fluenced favorably, because of the experi- patients, but that this was not a statistically second-line treatment of recurrent or meta- ence with another PD1 – [Bristol’s] Opdivo significant result. static head and neck cancer. Opdivo dem- – which has shown a statistically significant Keytruda received accelerated approval onstrated an overall survival benefit in the improvement in OS in this setting. The from the FDA for squamous cell carcinoma CheckMate 141 study, reducing the risk of vast majority of experts think that the vari- of the head and neck (SCCHN or HNSCC) in death by about 30%, compared to investi- ous PD-1s all have the same clinical profile, August 2016 based on data from the KEY- gator’s choice of methotrexate, docetaxel or meaning the FDA does not likely view Key- NOTE-012 study, in which the drug demon- Eli Lilly & Co.’s Erbitux (cetuximab). truda as providing no benefit in head and strated an objective response rate of 16% in Merck has other registration-enabling neck,” Bernstein’s Anderson said. a cohort of head and neck cancer patients. studies (KEYNOTE-048 and KEYNOTE-412) Bernstein noted that Merck had sales of (Also see “Keeping Track: Opana ER Abuse ongoing to assess different Keytruda mono- $584m in the first quarter and projects sales Deterrence Claim Withdrawn; Third Neulasta therapy and combination regimens in vari- of $737m in the second quarter. Biosimilar Submitted; Keytruda Cleared In ous head and neck cancer treatment settings. “The proportion coming from head and Head And Neck Cancer” Scrip, 12 Aug, 2016.) neck has been shrinking as Keytruda utiliza- “We have already discussed these data MERCK ARRIVES WHERE tion continues to ramp up sharply in lung with the FDA and do not anticipate any ROCHE FAILED BEFORE cancer, both as monotherapy and in combi- changes to the current HNSCC indication at PD-1 and L1 inhibitors have enjoyed enor- nation with chemotherapy,” Anderson said. this time,” Merck told Scrip. mous success, but the failure in head and Merck is due to report second-quarter SCHHN cancers caused by the sexually neck cancer is not the first for the check- earnings on July 28. transmitted disease HPV have been on the point family. Published 24 July 2017

10 | Scrip intelligence | 4 August 2017 © Informa UK Ltd 2017 QUARTERLY RESULTS

Lilly Hopes To Revitalize Its Cancer Brand With ‘Foundational’ Agents JOSEPH HAAS [email protected]

li Lilly & Co.’s revamped oncology research and development cancers. The drug is also being studied in tandem with Merck & Co. strategy, and an estimated 18-month delay in refiling the US Inc.’s PD-1 inhibitor Keytruda (pembrolizumab) in lung cancer. ENDA for its rheumatoid arthritis candidate baricitinib, overshad- Abemaciclib, a selective inhibitor of cyclin-dependent kinases owed a strong earnings quarterly report on July 25, as the Indianapo- (CDK) 4/6, is under priority review at the FDA in metastatic estrogen lis pharma reported 8% year-over-year sales growth overall, including receptor-positive HER2-negative breast cancer. It “could represent a 15% growth in its US business. potential best-in-class CDK4/6 inhibitor based on the totality of the Analysts were not overly impressed with the new cancer R&D data, including magnitude and depth of response as well as progres- plans – outlined by Lilly oncology president Susan Mahony and re- sion-free survival,” Mahony asserted, but it is entering a crowded field. cent hire Levi Garraway, senior VP of global development and medi- In a same-day note, Bernstein analyst Tim Anderson expressed cal affairs for oncology, who joined Lilly in January from Harvard Uni- skepticism about the best-in-class prediction, saying it was unlikely versity. Following a review of Lilly’s oncology pipeline and strategy, to outperform Pfizer Inc.’s Ibrance (palbociclib) despite Lilly touting the company has decided to partner or out-license several pipeline upcoming Phase III MONARCH-3 data it will unveil at the European cancer assets while increasing focus on several others that it believes Society for Medical Oncology (ESMO) conference this September in can become “foundational” agents in cancer care. Madrid. When those data testing abemaciclib along with aromatase Mahony told the earnings call that Alimta (pemetrexed), Erbitux inhibitor therapy in HR-positive/HER2-negative breast cancer are re- (cetuximab), Cyramza (ramucirumab) and abemaciclib, which is leased, Anderson predicted people will do side-by-side evaluations awaiting approval in two breast cancer indications at the US FDA, that will not make a clear case for abemaciclib superiority to Ibrance. give Lilly “a strong base from which to grow our oncology business.” Overall, Anderson said the Lilly cancer R&D strategy revamp Mahony and Garraway’s review resulted in a two-pillar strategy, she “sounded like ‘oncology 101’ to us, with the company primarily mak- explained: build upon key on- or near-market drugs that offer the po- ing broad generalizations that any company worth its salt in drug tential to be foundational, and pursue new standard-of-care agents development would make.” Lilly has not been at the forefront of the that create a very high bar for the competition to match or exceed. oncology field in years. “We intend to pursue breakthrough molecules across a variety of The priority cancer development candidates selected by Lilly mechanisms, including, but not limited to, immuno-oncology,” Ma- include a Phase I inhibitor of ERK1/2, which Garraway called a key hony explained. The mention of IO specifically is notable as Lilly has oncogenic driver in many cancers including RAS mutant cancers; a not been involved in the massively expanding field, unlike cancer- Phase II, first-in-class CHK1 inhibitor called prexasertib being tested focused companies like Bristol-Myers Squibb Co., Roche and No- in ovarian cancer; and a TIM-3 monoclonal antibody that has just vartis AG – among many others. Lilly has a mere handful of clinical entered clinical development. Garraway called TIM-3 “a PD-1-like im- candidates, none in late-stage development. mune checkpoint [that] resides on the surface of T-cells and tends “Key to our efforts will be leveraging advances in scientific under- to be activated at later stages of effector T-cell function than PD-1 standing to identify targets with a strong biological rationale, and we in what are often called exhausted T cells.” Lilly sees this candidate as will focus on targets that attack human dependencies or overcome offering synergy with anti-PD-1 therapies, including enhancing the resistance in reaching the target population to drive a larger benefit.” activity of those drugs. Garraway said Lilly will define foundational drugs as those that “in- The priority internal development candidates also include a Phase hibit a key dependency within the tumor. That is, a target or pathway II PI3K/mTOR inhibitor, a Phase I PD-L1 inhibitor and a Phase I TGFbeta essential to the viability of the malignant cells themselves or their R1 kinase inhibitor. Beyond those, Garraway said Lilly needs further ability to fend off the immune system.” He added that Lilly has de- data before making go/no-go decisions on three other clinical can- veloped a set of “rigorous and standardized criteria” to determine didates: merestinib, a Phase II multi-kinase inhibitor being studied in whether a candidate offers foundational potential, which can be biliary tract cancer, as well as two Phase I antibody candidates, one applied to both internal assets and external ones Lilly is considering against CSF1R and the other against AIMS 2. bringing in. Lilly also specified 10 oncology pipeline assets – four in Phase I and six in Phase II – that either are already partnered or that it will seek CYRAMZA LABEL EXPANSION, AGGRESSIVE to partner or out-license, including Phase II kinase inhibitors galu- ABEMACICLIB PROGRAM PLANNED nasertib and ralimetinib. In addition to out-licensing efforts, Mahony Mahony said label-expansion efforts for Cyramza – now approved said Lilly will become more aggressive in bringing in external cancer for gastric and non-small cell lung cancer – will play a key role in the assets, especially early-stage and preclinical candidates. “Specifically, new cancer strategy. Lilly hopes to expand Cyramza use to first-line we will actively pursue assets that combine rationally with our exist- gastric cancer and second-line urothelial cancer and is awaiting ing products, serve as new potential foundational agents and enable Phase III data from trials investigating the VEGF receptor 2-binding new IO breakthroughs,” she noted. antibody in liver cancer and first-line treatment of EGFR-mutant lung Published online 25 July 2017

scrip.pharmamedtechbi.com 4 August 2017 | Scrip intelligence | 11 QUARTERLY RESULTS

Celgene Eases Angst Over Otezla MANDY JACKSON [email protected]

here were no major surprises in Cel- ness, said during the second quarter earn- longer term and offset headwinds associated gene Corp.’s second quarter earnings call that Otezla’s growth was “driven by with increased discounts and rebates.” T ings, but the financial report did continued gains in treatment adoption, geo- As for opportunities outside of the drug’s ease anxiety about Otezla (apremilast) – the graphic expansion and improved market ac- two approved indications, Curran noted first major product to help the company cess with reimbursement now secure across that Celgene has “advanced multiple future diversify its portfolio beyond the Revlimid key European markets, and in Japan uptake growth drivers for Otezla, namely initiating (lenalidomide)-led hematology and oncol- is accelerating rapidly. Ex-US sales have more enrollment of the Phase III scalp psoriasis trial ogy franchise. than doubled versus last year.” and completion of enrollment for both the Investors were caught off guard by Cel- Curran said Otezla’s 2017 sales now are Phase II study in ulcerative colitis and Phase gene’s first quarter earnings report when expected to end up somewhere in the lower III trial in Behcet’s disease,” she said. sales for the psoriasis and psoriatic arthritis half of Celgene’s full-year forecast of $1.5bn drug Otezla fell 21% from the prior quarter to $1.7bn, helped by a growing number REVLIMID SALES RISE despite a 24% rise on a year-over-year basis. of prescriptions written in the US and a ris- AS CATALYSTS MOUNT However, the company said on July 27 that ing share of new-to-brand patients in both Celgene’s top-selling product Revlimid Otezla’s sales growth is back on track as of psoriasis and psoriatic arthritis. Both of those also has several upcoming catalysts in its the second quarter after negotiations with factors are helped by the company’s success largest indication, multiple myeloma, and payers yielded higher discounts and better in getting more US payers to provide reim- other hematologic malignancies. Sales of formulary placement. Celgene also high- bursement for patients who haven’t already the immunomodulatory drug increased lighted forthcoming clinical and regulatory undergone treatment with established bio- 20% year-over-year to $2.03bn – nearly catalysts for the PDE4 inhibitor and several logics. Ex-US launches, particularly in markets two-thirds of the company’s total revenue other approved therapies and drug candi- like France and Japan, have exceeded expec- in the second quarter. dates, including multiple readouts yet to tations, Curran noted. Rising Revlimid revenue came from income this year. “While still very early in the transition, we creased use globally and increasing durations Celgene’s total revenue rose 19% in the are encouraged by the material rebound in of therapy. Treatment periods have been ex- second quarter to $3.27bn versus $2.75bn the Otezla revenue trajectory in the second tended by the addition of a third agent for for the same period last year, beating analyst quarter, and based on the current operating certain patients with multiple myeloma in consensus of $3.23bn. Net product sales also trends, we view 2017 revenue guidance of the US. In Europe, more patients are receiving rose 19% year-over-year to $3.26bn, includ- $1.5bn to $1.7bn as achievable,” William Blair Revlimid in second-line treatment of multiple ing $358m in Otezla sales, which were up analyst Andy Hsieh wrote in a July 27 note. myeloma instead of the drug being reserved 48% from the first quarter and grew 49% ver- “Ultimately, we reiterate our opinion that the only for later lines of therapy. sus the second quarter of 2016. new market access strategy, which affects up Michael Pehl, president of Celgene’s global Terrie Curran, president of the company’s to 100m covered lives, will likely lead to more hematology and oncology business, said dur- global inflammation and immunology busi- robust market share gains for Otezla over the ing the company’s earnings call that while the

Selected Celgene 2H17 Regulatory And Clinical Catalysts

DRUG PARTNER CATALYST

FDA approval decision in relapsed or refractory acute myeloid leukemia (AML) with an Idhifa (enasidenib) Agios Pharmaceuticals Inc. IDH2 mutation due by Aug. 30. Otezla Submission of a supplemental NDA (sNDA) for a once-daily formulation Results from the Phase III apact (PANC-003) study as an adjuvant therapy for patients with Purchased in the 2010 surgically resected pancreatic cancer and from the Phase II abound.2L+ study in second Abraxane (nab-paclitaxel) acquisition of Abraxis or third line treatment of non-small cell lung cancer (NSCLC) in combination with the BioScience Inc. company’s CC-486 or AstraZeneca PLC’s Imfinzi (durvalumab). Phase I/II results in relapsed or refractory multiple myeloma (RRMM); initiation of a pivotal CC-122 trial in relapsed and/or refractory DLBCL Data from the Phase I/II FUSION program testing AstraZeneca’s PD-L1 inhibitor Imfinzi Vidaza (azacitidine) and with Pomalyst in multiple myeloma and with Vidaza in AML and myelodysplastic syn- Pomalyst (pomalidomide) dromes (MDS) Licensed from Nogra Mongersen (GED-0301) Phase II results in ulcerative colitis Pharma Ltd. in 2014 Otezla Phase II results in ulcerative colitis

12 | Scrip intelligence | 4 August 2017 © Informa UK Ltd 2017 QUARTERLY RESULTS/DEALS

duration of treatment extends to about 14 or favoring increased use of oral therapies, and 15 months in Europe, in the US “our treatment there is an unmet need for the MS indication Lilly/Nektar’s duration is way above 20 months.” for an oral therapy that’s both efficacious and ‘Stimulating’ The development plan for Revlimid never tolerable,” Curran said. does seem to slow down as new indications She described the market as “a sweet spot IL-2 Drug constantly are being added in the US and for Celgene. There’s a small prescriber base – other markets. about 3,000 physicians in the US prescribe Nektar Therapeutics used its own Celgene expects to report Phase III results 80% of treatments. So what’s on the critical expertise in targeting the interleu- during the second half of 2017 for Revlimid path for us right now is really establishing kin-2 (IL-2) receptor for immuno- in combination with Rituxan (rituximab) both our medical and our commercial orga- oncology to rapidly advance another for the treatment of newly diagnosed and nization, engaging with the market access novel compound with a different relapsed or refractory follicular lymphoma folks and looking at our pricing strategy.” approach to the target, and now the (the RELEVANCE and AUGMENT clinical tri- However, the inflammation and immunol- company’s tapping into Eli Lilly als). The combination has a tough act to fol- ogy head indicated that it’s too early for the & Co.’s experience in autoimmune low after Roche/Genentech Inc. reported company to begin talking publicly about its diseases to take NKTR-358 forward in potentially practice-changing results in ozanimod pricing plans. multiple indications. December for the Rituxan follow-on drug The rest of Celgene’s regulatory and clini- Lilly committed $150m up front and up to $250m in development Gazyva (obinutuzumab) in the treatment cal trial catalysts for the second half of 2017 and regulatory milestone fees of first-line follicular lymphoma. span the company’s hematology/oncology under its deal with Nektar, which Celgene also is testing Revlimid in com- and inflammation/immunology franchises, was announced July 24, plus double- bination with Rituxan-plus-chemotherapy per the table below. digit royalties and an opportunity (R-CHOP) in the treatment of activated B-cell Celgene also will begin pivotal trials in the for the San Francisco-based firm to subtype (ABC-type) diffuse large B-cell lym- second half of 2017 for the proteasome in- participate in US commercialization phoma (DLBCL) with results from the Phase hibitor marizomib in first-line glioblastoma, of NKTR-358. The drug is designed III ROBUST trial expected in 2018. which it acquired from Triphase Accelera- to stimulate the proliferation of “We are particularly excited about the tor Corp.; for the BCMA-targeting bb2121 regulatory T-cells (Tregs), a type Phase III ROBUST study,” William Blair’s Hsieh in RRMM in collaboration with bluebird bio of inhibitory immune cell that’s wrote. “Given DLBCL is the largest subtype Inc.; and for the chimeric antigen receptor T become of interest to many biop- among newly diagnosed lymphoma popu- cell (CAR-T) therapy JCAR017 in relapsed or harmaceutical companies, including lations, combined with the fact that Revlimid refractory LDBCL with partner Juno Thera- Celgene Corp. has historically demonstrated the highest peutics Inc. Celgene did not provide much additional activity among DLBCL with the ABC subtype, Acquisition we are cautiously optimistic of the outcome color on the acquisition of rights to BeiGene Celgene paid $300m up front earlier and believe the study could provide material (Beijing) Co. Ltd.’s PD-1 inhibitor BGB-A317 this year to acquire the startup Delinia upside to current expectations.” during the company’s earnings call, but exec- Inc. and its preclinical pipeline of Treg- utives emphasized the importance of the as- targeting therapies that may be able OZANIMOD SUBMISSION, IDHIFA set to its overall immuno-oncology strategy, to treat autoimmune diseases without APPROVAL COMING SOON which is dominated by combination therapy suppressing the immune system. Delin- One of the most highly anticipated second approaches. ia’s investors could earn up to $475m in half of 2017 catalysts for the company, how- “Celgene believes BGB-A317 to be ‘poten- additional milestone fees as those assets ever, is outside of its blockbuster hematol- tially’ differentiated based on the preclinical progress in clinical development. ogy and oncology franchise. Celgene ex- data so far, but it remains to be shown in Nektar senior vice president-biolo- pects to file a new drug application (NDA) the clinic,” Mizuho Securities analyst Salim gy and preclinical development Jona- with the US FDA by the end of the year for Syed noted in a July 27 report. “Celgene than Zalevsky, whose team discov- ozanimod in the treatment of multiple scle- hasn’t ruled out any combinations with other ered NKTR-358 and conducted the rosis (MS) after reporting two sets of positive drugs/mechanisms.” research to support a Phase I clinical Phase III data for the oral selective sphingo- CEO Mark Alles noted that PARP inhibitors trial that started in March, said in an sine 1-phosphate 1 (S1P1) and 5 receptor are one potential class not already in Cel- interview that immune stimulation modulator earlier this year. gene’s portfolio that the company may con- without suppression is a sort of “holy It still was unknown when Celgene re- sider combining with BGB-A317, but more grail” in the treatment of autoim- vealed the Phase III RADIANCE results in May details about its immuno-oncology plans will mune diseases. whether the company would commercialize be revealed around the American Society of its first neurology product on its own or with Hematology (ASH) meeting in December. [email protected] a partner, but preparations are under way to It’s been rumored that Clovis Oncology 24 July 2017 launch without the aid of an experienced Inc., developer of the PARP inhibitor Rub- Read more about the companies’ next collaborator. “From a market opportunity, we raca (rucaparib), is an acquisition target for steps here: http://bit.ly/2wehEVl really do see the MS treatment paradigms Celgene. Published online 27 July 2017 scrip.pharmamedtechbi.com 4 August 2017 | Scrip intelligence | 13 BUSINESS STRATEGY

Biogen’s Neuroscience Strategy Includes De-Risking The Pipeline JESSICA MERRILL [email protected]

iogen Inc. is tightly focused on establishing a leadership posi- “We aim to demonstrate that we can advance a broader world- tion in the high risk field of neuroscience, and the company’s class neuroscience pipeline beyond just Alzheimer’s disease,” the Bpipeline, heavily-weighted toward that therapeutic area, has chief executive added. made some investors nervous. But CEO Michel Vounatsos and Exec Ehlers further downplayed the company’s reliance on aducanum- VP-R&D Michael Ehlers talked about rebalancing risk in a strategy up- ab. “While we continue to see tremendous opportunity for the Al- date during the company’s second quarter earnings call on July 25. zheimer’s disease franchise, we believe we can achieve our aspiration The company’s strategy, according to the new CEO, will be and become the fastest-growing large cap biotech even without to invest for the future across four core therapeutic areas: mul- aducanumab.” tiple sclerosis and immunology; Alzheimer’s disease and dementia; The company will trade its emphasis on share repurchase to di- Parkinson’s disease and related movement disorders; and neuromus- rect more resources toward business development, he said. When it cular disease, including spinal muscular atrophy (SMA) and amyo- comes to BD, the company is emphasizing early-stage clinical assets, trophic lateral sclerosis (ALS). but will also remain proactive in evaluating later-stage opportunities. “Further, we see opportunities to invest in emerging growth areas Biogen also aims to improve internal R&D and plans to increase in- such as pain, ophthalmology, neuro-psychiatry and acute neurology,” vestment in the area, redirecting $400m to high-value R&D opportu- he said. nities by streamlining operations. As Ehlers explained it, “We remain focused on neuroscience, but The company is bullish about expanding its expertise in antisense widening our lens of potential opportunities.” oligonucleotides and intrathecal injection, through its learnings on “Our strategy takes a multipronged approach to both expand and Spinraza with partner Ionis Pharmaceuticals Inc., to other oppor- de-risk our pipeline, including an increased emphasis on business tunities. In an interview earlier this year, Ehlers talked about how development and diversification across disease area and therapeutic advances in technology are creating new opportunities for neuro- approach,” Ehlers said. science drug development. (Also see “Neuroscience Reaches A New The expectation is for cash flow to grow in the near-term, driven Inflection Point, Big Biotechs Say” Scrip, 24 Jan, 2017.) by existing commercial products, including the multiple sclerosis “We see an opportunity to leverage Biogen’s capabilities and rebal- blockbuster Tecfidera (dimethyl fumerate) and the new Spinraza ance pipeline risk by emphasizing rare neurological and neuromus- (nusinersen) for SMA. The launch of Spinraza for the ultra-rare indi- cular disease, including genetic subsets of more common diseases cation is outperforming expectations, which is helping Biogen build such as Parkinson’s disease, ALS and tauopathies,” Ehlers said. its case to investors. The company’s recent business development activity highlights Biogen reported second quarter sales of Spinraza of $203m, sub- that strategy. In April, Biogen signed a licensing deal with Bristol- stantially outpacing analyst consensus estimates of $70m. Spin- Myers Squibb Co. to in-license a Phase II tau antibody in develop- raza, the first antisense oligonucleotide to reach the market, was ment for Alzheimer’s disease and progressive supranuclear palsey approved by the FDA in December for the rare deadly neurodegen- (PSP), a neurological tauopathy. erative disease characterized by a missing or defective SMN1 gene. The company followed up in May with a licensing deal for rights (Also see “Biogen Staying “Laser-Focused” On Neuroscience” Scrip, 25 to Remedy Pharmaceuticals Inc.’s Cirara (intravenous glyburide) in Apr, 2017.) It’s delivered via intrathecal injection through the spinal development for a certain type of severe stroke in which brain swell- cord to bypass the blood-brain barrier. ing leads to a large share of stroke-related morbidity and mortality. “This cash flow will enable us to invest in and build an industry- (Also see “Biogen Builds Out Neuroscience Niche With Ischemic Stroke leading neuroscience pipeline that we believe will transform Biogen Drug” Scrip, 15 May, 2017.) into the fastest growing large-cap biotech company,” Vounatsos said. Biogen’s strong second quarter financial results, which led management to raise guidance for the year, is helping to assuage in- ADUCANUMAB: POTENTIALLY TRANSFORMATIVE vestor concerns about the near-term growth prospects for the BUT NOT A MUST company, given the increasingly competitive dynamics in mul- The inflection point for Biogen will come in the early 2020s, he said, tiple sclerosis. Total revenues grew 6.1% to $3.1bn; revenues were when multiple high-value assets either launch or have data readouts. up 15% excluding hemophilia sales in the prior-year quarter. The The potentially transformative opportunity for the company is the company spun out its hemophilia business into a new company, anti-beta amyloid drug aducanumab for Alzheimer’s disease, ac- Bioverativ Inc., in February. cording to Vounatsos. The high-profile asset generated some posi- Sales of Tecfidera increased 13% to $1.11bn, representing strong tive early data, but is nonetheless considered high-risk by investors growth in a category that saw new competition from Roche’s Ocre- given the wide-ranging failures in Alzheimer’s drug development. vus (ocrelizumab). Net income of $862.8m was lower in the second Aducanumab is being tested in a Phase III trial that is expected to be quarter compared to a year ago due to the business separation. fully enrolled in 2018. Published online 25 July 2017

14 | Scrip intelligence | 4 August 2017 © Informa UK Ltd 2017 BUSINESS STRATEGY

J&J Prepares For US Sirukumab Launch After Regaining Rights From GSK JESSICA MERRILL [email protected]

ond biosimilar competitor to Remicade, Renflexis (infliximab-abda). (Also see “Merck’s Second-To-Market Renflexis Biosimilar Priced Below The First” Scrip, 24 Jul, 2017.) J&J has been hoping sirukumab will help the company make up some of the revenue it could lose as biosimilars and other competitive dynamics begin to chip away at Remicade. The company expects sirukumab and another new launch, Tremfya (guselkumab) for psoriasis to drive immunology growth in the near-term. (Also see “J&J Forges Ahead In Immunology Despite Competitive Dynamics” Scrip, 18 May, 2017.) Tremfya is a first-in-class IL-23 blocker approved by the FDA on July 13. (Also see “J&J’s First-In-Class Tremfya Poised To Join A Crowded Psoriasis Market” Scrip, 14 Jul, 2017.) Given the competitive dynamics in RA, the decision by GSK to back out of the commercial launch isn’t altogether surprising, es- Shutterstock: Ehrman Photographic Ehrman Shutterstock: pecially given GSK’s inexperience in the field of immunology. None- theless, the company has targeted the therapeutic area as a pillar ohnson & Johnson will need to move quickly to prepare for for the future, and in an interview last year chief immunology offi- the US commercialization of the interleukin-6 inhibitor siruku- cer Paul-Peter Tak said the drug would be an anchor from which to Jmab after GlaxoSmithKline PLC returned rights to the drug launch future more innovative medicines. (Also see “GSK’s Immunol- in North America, Central America and South America. The drug is ogy Strategy Edges Closer To Delivering” Scrip, 27 Sep, 2016.) pending at the FDA for the treatment of rheumatoid arthritis with “The group is making a number of choices to prioritize the stron- action expected soon, sometime in the third quarter. gest assets and markets in its portfolio and move capital and re- In a sudden turn of events, GSK announced July 26 with the resources away from those that offer more limited opportunities,” GSK lease of its second quarter financials that it would return rights to said in a statement. sirukumab and slowly withdraw commercial investment behind Like sirukumab, Tanzeum was also a latecomer in competitive the GLP-1 agonist Tanzeum (albiglutide) for type 2 diabetes as part therapeutic area. The company hailed Tanzeum as GSK’s return to of a portfolio reorganization under new CEO Emma Walmsley. diabetes when it launched in 2014 and as a late entrant, sought to J&J partnered with GSK on the co-development and co-com- compete on price. (Also see “GSK’s Tanzeum Launch Marks The Big mercialization of sirukumab in 2011 and the two initiated the Phase Pharma’s Return To Diabetes” Scrip, 28 Jul, 2014.) But Tanzeum never III development program in 2012. Under the agreement, GSK regained a foothold in a market dominated by Novo Nordisk AS’s tained commercial rights to the US and other American markets, Victoza, AstraZeneca PLC’s Byetta/Bydureon (exenatide) and Eli while J&J retained rights in other parts of the world. Lilly & Co.’s Trulicity (dulaglutide). Tanzeum only generated £51m “We have been preparing for the introduction of sirukumab in in the first half of 2017. EMEA and Asia-Pacific market, where Janssen has held rights,” a Published online 26 July 2017 company spokesperson said. “We will now also turn our attention to markets like the US that will return to Janssen.” “While we can’t comment on specific plans at this time, pending a FDA approval of sirukumab, our aim would be to ensure sirukumab is available for patients who may benefit from this anti-IL-6 therapeutic.” LET’S GET The commercial prospects for sirukumab have been uncertain, given that it will be the third IL-6 inhibitor to reach the US market, behind Roche’s Actemra (tocilizumab) and Regeneron Pharma- SOCIAL ceuticals Inc./Sanofi’s Kevzara (sarilumab), which was approved We are tweeting, liking and sharing the latest by the FDA in May. (Also see “Sanofi/Regeneron’s Kevzara Priced To industry news and insights from our global Break Into A Crowded Market” Scrip, 23 May, 2017.) Outside of the class, the market for rheumatoid arthritis is also crowded, led by team of editors and analysts, join us! the anti-TNFs, including AbbVie Inc.’s Humira (adalimumab) and Johnson & Johnson’s own Remicade (infliximab), which itself is fac- @PharmaScrip ing biosimilar competition. Merck & Co. Inc. just launched the sec-

scrip.pharmamedtechbi.com 4 August 2017 | Scrip intelligence | 15 IMMUNO-ONCOLOGY OUTLOOK

PD-1 Data Emerge In Cervical Cancer LUCIE ELLIS [email protected]

ancer of the uterine cervix, or cervi- (Topo-I) inhibitor that lost patent protec- from its Phase I/II trial of the PD-1 inhibi- cal cancer, is the second most com- tion in 2010, is the only other drug spe- tor in combination with Lovaxin C (axali- Cmon form of cancer among women cifically indicated for cervical cancer in mogene filolisbac) at a medical meeting worldwide, with approximately 500,000 the US and Europe. in the second half of 2017. Lovaxin C is new cases reported each year. a Listeria-based vaccine which targets a However, while the pipeline for vac- PD-1S IN CERVICAL CANCER cytotoxic immune response against the cines aimed at preventing the disease is Drug development in cervical cancer is fo- antigen HPV-E7. vast, treatment options are limited. Novel cused mainly on prevention; there are sev- Advaxis plans to initiate a second glob- immunotherapy drugs that have become eral HPV vaccines already on the market and al, Phase III randomized registrational standard of care treatments in other can- more in the clinic. study for Lovaxin C as a monotherapy in cers are new to the cervical cancer space However, immunotherapy options are patients with metastatic cervical cancer and clinical development is still in the starting to be explored in cervical cancer later this year. Biomedtracker analysts early stages. and three program cell death protein-1 (PD- expect the company will file the vaccine 1) inhibitors and one program death-ligand product in Europe in the fourth quarter of 1 (PD-L1) product are in early clinical devel- 2017 using data from a previous Phase III opment. trial in second- and third-line metastatic Bristol-Myers Squibb Co. PD-1 in- cervical cancer. When Advaxis conducted hibitor Opdivo (nivolumab) is the most this first trial, known as the AIM2CERV advanced checkpoint inhibitor in the (Advaxis IMmunotherapy 2 prevent CER- clinic for recurrent or metastatic cervical Vical recurrence) study, it was the only cancer. The company presented the first company-sponsored, global Phase III trial data from the Phase I/II CheckMate 358 enrolling patients with advanced stage trial at the American Society for Clinical cervical cancer. Oncology’s annual meeting in June this year. The trial is evaluating Opdivo for the OTHER APPROACHES treatment of patients with advanced cer- Beside the PD-1 inhibitors and Lovaxin C vical, vaginal and vulvar cancers, all asso- there are a handful of other drugs in the ciated with infection by HPV. cervical cancer pipeline, including vac- New immunotherapy options are The cohort of the CheckMate 358 study cines and small molecules, that are using emerging in the cervical cancer pipeline

Shutterstock: Sanit Fuangnakhon Sanit Shutterstock: presented at ASCO included 24 patients, different mechanisms of action against 19 of whom were cervical cancer pa- various targets. Included in this are three Human Papillomavirus (HPV), which tients. The primary efficacy endpoint of cell therapies in early clinical trials: Kite is transmitted through sexual contact, the trial is objective response rate. Re- Pharma Inc.’s E6 TCR, Iovance Biothera- is linked with more than 90% of cervical sponses were seen only in cervical cancer peutics Inc.’s LN-145 and Tessa Therapeu- cancers, about 75% of vaginal cancers patients; of the 19 women, five had com- tics Ltd.’s TT12 HP-VST. and 69% of vulvar cancers. First-line treat- plete and partial responses, with an ORR LN-145, an autologous cell therapy ment for women with advanced cervical of 26.3%. Median duration of response product derived from patient tumor-infil- cancer often consists of chemotherapy has not been reached after 6 months of trating lymphocytes (TILs), is the most ad- alone or combined with radiation, and the follow-up. vanced cell therapy candidate in the clin- five-year survival rate for advanced cervi- Merck & Co. Inc.’s Keytruda (pem- ic. Iovance (formally Lion Biotechnologies, cal cancer, stages III and IV, ranges from brolizumab) and Agenus Inc.’s investi- Inc) launched a Phase II study to evaluate about 35% to 16%. After first-line therapy, gational therapy AGEN2034, both PD-1 the safety, tolerability and efficacy of cell options are limited for women with gyne- inhibitors, as well as AstraZeneca PLC’s transfer therapy using LN-145 followed cologic tumors. PD-L1 therapy Imfinzi (durvalumab), are by IL-2 in patients with recurrent and/or Roche’s blockbuster cancer therapy also in early-stage clinical trials for cervi- metastatic cervical carcinoma in April this Avastin (bevacizumab), a vascular en- cal cancer. year. The company plans to enroll 47 pa- dothelial growth factor (VEGF) inhibitor, Opdivo, Keytruda and Imfinzi are al- tients in the study. is currently the only branded drug ap- ready on the market in the US and Eu- Kite’s E6 TCR completed a Phase I/II trial in proved for cervical cancer. Avastin will rope for the treatment of various other June this year in patients with HPV-related begin to lose market exclusivity in the cancers. cancers. Meanwhile, Tessa’s TT12 HP-VST has US in July 2019 and in Europe in January Advaxis Inc., AstraZeneca’s develop- completed Phase I, with a Phase II study ex- 2022. Novartis AG’s Hycamtin (topote- ment partner for Imfinzi in cervical can- pected in the next 18 months. can hydrochloride), a topoisomerase I cer, expects to report updated results Published online 26 July 2017

16 | Scrip intelligence | 4 August 2017 © Informa UK Ltd 2017 QUARTERLY RESULTS

Roche Lifts Outlook, Spotlights Perjeta To Drive Growth JOHN DAVIS [email protected]

Roche’s sales growth was particularly Severin Schwan, CEO of Roche pronounced in the US and in international markets, while European sales were flat, Schwan reported. Sales in the US grew by 8% and were led by Tecentriq, Xolair (omalizumab), MabThera/Rituxan (rituximab) and Ocrevus. Sales of Avastin (bevacizumab) declined by 1% compared with the 1H 2016, partly due to the drug being delisted from reimbursement for breast cancer in France. Avas- tin sales were also affected by increased competition from immunotherapies in the treatment of lung cancer, Roche noted.

IMPORTANCE OF APHINITY For Roche’s outlook, Schwan underlined what he saw as the importance of the recently released APHINITY study data on the use of Perjeta (pertuzumab) in combination with Herceptin (trastuzumab) in the he CEO of Switzerland’s big pharma we needed it,” said the CEO of Roche Phar- adjuvant setting for early-stage breast can- company Roche, Severin Schwan, maceuticals, Daniel O’Day. cer. His views were somewhat at odds with has categorized the launch of the T Schwan noted there was only very limited the underwhelming response given to the new multiple sclerosis therapy Ocrevus impact from biosimilar competitors in the data by analysts when it was released. (ocrelizumab) in the first half of 2017 as “par- first half of 2017 but said such competition (Also see “APHINITY Combo Details Contain ticularly pleasing,” a “phenomenal start,” and was expected to gradually increase during No Surprise, Puma’s Nerlynx May Benefit” “even above our own expectations.” the second half of 2017 and into 2018. Scrip, 5 Jun, 2017.) There was strong underlying demand for Ocrevus, Tecentriq and Alecensa, contrib- “Today, Perjeta sales are already above Ocrevus across its two indications, relapsing uted CHF500m ($518m) in new sales dur- CHF2bn on an annualized basis, they grew multiple sclerosis (RMS) and primary pro- ing the first half of 2017 and the three new by 17% in the first six months. So, the medi- gressive multiple sclerosis, Schwan noted. products accounted for half of the sales cine is doing very well in the metastatic set- Between 5,000 and 6,000 patients were growth in Roche’s pharmaceutical division, ting, and now based on the APHINITY data treated with Ocrevus in the first half of 2017 where sales rose by 5% compared with the we will bring this important medicine to the in the US, and Australia has also approved 2016 first half, to CHF 20.5bn. early-stage setting,” Schwan remarked. the product. An EU approval is expected by The good financial results over the 2017 “We are talking about early-stage breast the end of the year. first half led Roche executives to announce cancer, where we have seen an over- Two other newly launched medicines, the they were raising the company’s financial all 19% risk reduction in recurrence and anticancer Alecensa (alectinib), which is in- outlook for the year, something that ana- death. This is highly meaningful data, a dicated for first-line ALK-positive non-small lysts had been calling for after a strong set view shared by many thought leaders in cell lung cancer, and the PD-L1 inhibitor, of results in the 2017 first quarter. (Also see this area,” he said. Tecentriq (atezolizumab), which is available “Roche Delivers Strong Quarter On Ocrevus Schwan added that he would look for- in the US, also did “very well” in the first six Launch, Pipeline Promise” Scrip, 27 Apr, 2017.) ward to filings for additional indications months of 2017, Schwan told a July 27 fi- Sales are now expected to grow by mid- based on the APHINITY data, and that he nancial results call with analysts. single digits, at constant exchange rates had no doubt that the product would be a There was just a hint of relief in com- (CERs), over the 12 months of 2017, and core substantial growth driver for the company ments made by top executives from earnings per share are expected to grow in the future. Roche, which could face increasing com- broadly in line with sales at CER, Schwan re- In the first half, group sales at Roche petition from biosimilar versions of some ported. Previously Roche had been guiding rose by 5% in Swiss Francs and at CER to of its mainstay products over coming for a low- to mid-single-digit sales growth CHF26.3bn, while net income increased by years. “The strong performance of the R&D rate over the 12 months, with a similar core 2% to CHF 5.6bn. pipeline has come at exactly the right time earnings per share growth. Published online 27 July 2017 scrip.pharmamedtechbi.com 4 August 2017 | Scrip intelligence | 17 QUARTERLY RESULTS

Amgen Beats Consensus, Raises Earnings Guidance, But Is It Sustainable? MANDY JACKSON [email protected]

mgen Inc.’s second quarter revenue of the year. (Also see “Amgen Hit By Enbrel driven by higher product demand, particu- of $5.81bn and non-GAAP earnings ‘Peculiarities’ And Repatha Resistance” Scrip, larly in ex-US markets. Aper share (EPS) of $3.27 beat con- 27 Apr, 2017.) “Prolia’s average share of treated patients sensus estimates, but revised financial guid- Mizuho Securities analyst Salim Syed is around 20%, both in the US and globally. ance for the full year painted a mixed pic- pointed out in a same-day research note However, there are some countries such ture, calling into question the sustainability that pressure on the product reported in the as Australia, Switzerland and Ireland where of the company’s growth. first quarter remained in the second quar- better diagnosis and treatment rates for The second quarter totals handily beat ter, including excess inventory that grew osteoporosis have led to Prolia having 50% consensus of $5.67bn in revenue and $3.11 to $120m by the end of March and rose to share or better,” executive vice president in non-GAAP EPS, but investors still sent $140m by the end of June. Amgen expects of global commercial operations Anthony Amgen’s stock down 2.4% in after-hours that inventory to be used up as the year Hooper said during Amgen’s call. “These are trading to $176.60 on July 25 following the goes on, but Syed noted that the company countries that truly understand the societal company’s conference call. The sentiment said the same thing in the first quarter and cost of nonintervention. Prolia has a strong reflected a quarterly financial report that that inventory buildup increased in the sec- clinical profile with a proven ability to re- didn’t promise any major growth catalysts ond quarter. duce risk of fractures.” in the near term to make up for blockbuster Neulasta experienced lower demand The biggest percentage gainer was Re- products that are losing momentum. Am- driven by a reduced incidence of neutrope- patha with a 218.5% year-over-year spike. All gen raised its 2017 EPS guidance to a range nia due to decreased use of chemotherapy $27m of the product’s sales during the sec- of $12.15 to $12.65 (from $12 to $12.60), but agents in the treatment of cancer – a result ond quarter of 2016 were in the US, so sec- lowered the top end of its revenue forecast of increased use of PD-1/L-1 inhibitors. Sales ond quarter 2017 US sales of $60m reflected to $23bn from $23.1bn, hinting that earn- dropped despite the launch of the on-body a 122.2% increase. Ex-US sales totaled $23m. ings growth would come from cost cuts injector Neulasta Onpro, which now ac- While Repatha sales surged, they rose off rather than sales gains. counts for about 55% of Neulasta sales. of a small base, and Amgen didn’t provide Chief financial officer David Meline said any reassurances that the PCSK9 inhibitor during Amgen’s conference call that the NEW PRODUCTS DON’T OFFSET would attain blockbuster status in the near- company delivered “consistent revenue and DECLINERS term based on the FOURIER cardiovascular earnings growth in the second quarter as Declines for Amgen’s top sellers were not outcomes trial results revealed at the Ameri- our transformation efforts continue to en- significantly offset by newer products, even can College of Cardiology (ACC) meeting able investment in our core business, while with sales for the PCSK9 inhibitor Repatha in March, since new high cholesterol treat- also delivering operating leverage in a pe- (evolocumab) – the biologic approved to ment guidelines incorporating the PCSK9 riod of portfolio transition and in a competi- treat high cholesterol in certain high-risk class won’t be finalized until late 2018. tive environment.” and statin-intolerant patients – tripling from Hooper also noted that the company Amgen spent an extra $71m on sales $27m in the second quarter of last year to will not promote these data to physicians and general administrative expenses in the $83m in the same period this year. until the US FDA and European Medicines second quarter than it did in the same pe- Sales for eight products increased in the Agency (EMA) approve Amgen’s applica- riod last year to deliver an extra $100m in April-to-June period by a total of $285m for tions submitted in the second quarter product sales, but it also saw research and an average gain of $35.6m, but sales de- asking the regulators to add the cardio- development spending decline by $10m as clined by $185m for five products and cat- vascular benefits seen in FOURIER to the programs shifted to different stages of de- egories – an average loss of $36m. Repatha label. velopment. Notably, the category reported as “other,” Even so, when Amgen chair and CEO Bob Sales of the company’s two biggest sellers which includes certain subsidiaries and Bradway mentioned Repatha in prepared are falling – the TNF inhibitor Enbrel (etan- newer products like Corlanor (ivabradine) remarks at the beginning of the company’s ercept) for arthritis and other inflammatory for heart failure and Imlygic (talimogene la- conference call, he said the drug will be “a conditions dropped 1% year-over-year to herparepvec) for melanoma, decreased 10% significant contributor to our long-term $1.47bn in the second quarter and the neu- to $61m. volume-driven growth.” tropenia treatment Neulasta (pegfilgrastim) The biggest dollar amount gainer in Am- fell 5% to $1.09bn. Enbrel recovered from a gen’s portfolio was the blockbuster osteo- OTHER GROWTH DRIVERS 15% decline in the first quarter, but sales of porosis drug Prolia (denosumab), which SHARED OR INCREMENTAL the biologic are expected to maintain the grew by $64m (15% year-over-year) to Amgen is developing several biosimilars of level seen in the second quarter for the rest $505m in the second quarter. The rise was marketed biologics, which eventually may

contribute to the company’s sales follow- Survival Benefit May Help Amgen’s Kyprolis Jefferies analyst Michael Yee, who is bull- ing the end of patent disputes with the Stave Off Competition” Scrip, 28 Feb, 2017.) ish about Amgen’s growth prospects in the original products’ developers. However, One of the few novel compounds with mid- and long-term, laid out the opposing biosimilars competing with Amgen’s own blockbuster potential that’s nearing regu- views of the company’s stock in a July 25 re- brand-name products aren’t expected to latory approvals is Aimovig (erenumab) for port on the company’s earnings. hurt US sales in the near term. CFO Meline migraine headaches, but that revenue will “Ultimately, we believe [the] stock con- said full-year 2017 sales and earnings guid- be shared with partner Novartis AG. tinues to rise, although [the] bigger pic- ance “assumes no new biosimilar competi- The FDA has accepted the biologic li- ture may take some patience … due to: 1) tion in the US in 2017.” cense application (BLA) for the CGRP in- inflection on PCSK9 in 2018 on [the] heels The company is feeling the impact of bio- hibitor Aimovig and set a May 17, 2018 of ACC guideline and the FDA label change similars marketed in the EU, however, with PDUFA date, portending the likely first next year, 2) Neulasta biosimilars falling to global sales of the shorter-acting neutrope- approval for the drug class. (Also see wayside (hard to have conviction yet), or 3) nia drug Neupogen (filgrastim) down 30% to “Response Rates Rule In CGRP Inhibitor Mi- a new pipeline drug comes on (e.g., Tezepe- $137m in the second quarter versus $196m graine Studies” Scrip, 12 Jun, 2017.) How- lumab for atopic dermatitis/asthma, etc.) in the year-ago period. ever, the osteoporosis candidate Evenity – but visibility [is] lower versus peers,” Yee Meanwhile, most of Amgen’s pipeline (romosozumab) recently was rejected wrote. “Bears will push back that [the] Enbrel progress over the next several months rep- and will be resubmitted to the agency franchise remains an Achilles heel if pricing resents incremental additions to the com- with data from the ARCH clinical trial. power dramatically weakens, Neulasta bio- mercial portfolio, including new indications (Also see “US FDA Sends Amgen/UCB Eve- similars are coming in time, PCSK9 launch in multiple myeloma for Kyprolis (carfilzo- nity Back With BRIDGE Request” Scrip, 17 remains tepid, and pipeline lacks material mib), as well as submissions and regulatory Jul, 2017.) That product’s revenue will be blockbusters at this time.” reviews for biosimilars. (Also see “Myeloma shared with UCB SA. Published online 26 July 2017

Bayer And Morphosys Brush Off ADC Mesothelioma Failure ALEX SHIMMINGS [email protected]

large Phase II trial of an antibody- gy, is taken up inside the tumor cells, where sothelioma indication, they are not yet ready drug conjugate anetumab ravtan- degrading enzymes release cytotoxic may- to discount the whole program. “Since me- Asine (BAY 949343) under develop- tansinoid tubulin inhibitor, DM4, which in- sothelin is a receptor overexpressed in many ment by Bayer AG and MorphoSys AG duces cell cycle arrest and apoptosis. cancers types, we are not ruling out the pros- has failed to show any benefit in recurrent The companies said the outcome was pect of positive results and/or efficacy trends malignant pleural mesothelioma, but the disappointing. “Malignant pleural mesotheli- in other ongoing trials. Hence Bayer’s com- companies are still hopeful of success in oma is a very difficult-to-treat tumor, and we mitment to the development programme other indications. had hoped for a better outcome for patients,” of anetumab across two Phase Ib trials in six The study, conducted by Bayer in 248 pa- admitted Robert LaCaze, executive vice pres- solid tumor types in ovarian cancer respec- tients with recurrent malignant pleural me- ident and head of Bayer’s oncology strategic tively,” commented analysts at Bryan Garnier sothelioma whose disease had progressed business unit. But he added that based on in a July 24 research note. The Phase Ib results after treatment with first-line platinum/ the available data, the company remained for the six solid tumor types should read out pemetrexed-based chemotherapy, did not committed to further evaluating the drug by the end of the year. meet the primary endpoint of progression- across a number of tumor types with signifi- Other upcoming milestones for Morphosys free survival when anetumab ravtansine cant unmet medical need. include Phase II results for its HuCAL based an- was used as a monotherapy (6.5 mg/kg Anetumab ravtansine is still being inves- tibody targeting CD38, MOR202, in multiple I.V. every three weeks) or in addition to tigated, as monotherapy and in combina- myeloma (a product for which it regained the vinorelbine (30 mg/m2 I.V. every week). No tion, in additional trials, including a Phase Ib rights from Celgene in 2015), and it should new safety issues were thrown up by the multi-indication study in six different types of soon book the first revenues from its deal wth study, the full results of which will be pre- advanced solid tumors, as well as a Phase Ib Johnson & Johnson under its licensing deal sented at an upcoming meeting. combination study in patients with recurrent for the first-in-class interleukin-23 inhibitor Anetumab ravtansine is targeted against platinum-resistant ovarian cancer. According guselkumab, which was recently approved as mesothelin, a surface marker protein over- to clinicaltrials.gov, the tumor types include Tremfya for moderate to severe plaque psoria- expressed in many cancers. After binding to cholangiocarcinoma, pancreatic, lung, triple sis. (Also see “J&J’s First-In-Class Tremfya Poised mesothelin, the antibody-drug conjugate, negative breast cancer and gastric cancer. To Join A Crowded Psoriasis Market” Scrip, 14 Jul, made using MorphoSys’s HuCAL technolo- Although analysts have written off the me- 2017.) Published online 24 July 2017 scrip.pharmamedtechbi.com 4 August 2017 | Scrip intelligence | 19 QUARTERLY RESULTS

Post-MYSTIC, Bristol Renews CTLA-4 Vows, But Is “Not Wedded” In Lung Cancer EMILY HAYES [email protected]

ristol-Myers Squibb Co. talked up that this is the second major PD-1 study to CTLA-4 class in order to minimize severe its commitment to the CTLA-4 check- fail in first-line NSCLC against platinum- toxicity and dropouts. Bpoint target, accentuating its strong based chemo, after Bristol’s Opdivo in the Barclays analyst Geoff Meacham com- qualities and track record, while also say- CheckMate 026 study. mented in a July 27 note that Bristol has ing it is “not wedded” to the CTLA-4/PD-1 MYSTIC’s loss is a gain for Merck & Co. done a better job with dosing schedules to combination in lung cancer and has lots of Inc.’s PD-1 inhibitor Keytruda (pembrolizum- minimize toxicity of the CTLA-4 component options, during its second-quarter earnings ab), which won accelerated approval in May of the combination. call on July 27. for first-line NSCLC, albeit in a highly selected The second quarter was another strong population in combination with certain MORE DOUBTS ON CTLA-4 one for Bristol and its super-successful types of chemotherapy, and based on very Investors’ skepticism about the CTLA-4 PD-1 inhibitor Opdivo (nivolumab), which early data from a cohort of the KEYNOTE- mechanism has been rising with apprecia- brought in sales of $1.19bn, up by 42% from 021G study. The Phase III KEYNOTE-189 tion of the severe toxicity in contrast to the the same quarter in 2016 and beating the study, due to report later this year, will be the tolerability of PD-1 monotherapy, changes Street’s expectations by $74m. A number real test for that drug in first-line NSCLC. to the designs of both MYSTIC and Check- of other key products bested expectations, Mate 227 combination trials and results from including the CTLA-4 checkpoint inhibitor BRISTOL’S RESPONSE the CheckMate 067 first-line melanoma Yervoy (ipilimumab) and the novel antico- Bristol’s second-quarter earnings call, un- study. In the -067 study, the Yervoy/Opdivo agulant Eliquis (apixaban) with $322m and surprisingly, wound up being dominated combination demonstrated superior effi- $1.17bn in sales, respectively. by execs responding to the MYSTIC news, cacy over Yervoy monotherapy but did not But the future of its Yervoy/Opdivo com- ahead of the release of the pharma’s own appear to add much benefit over Opdivo bination in the most valuable indication CheckMate 227 PD-1/CTLA-4 combina- alone to make the side effects worthwhile. for immunotherapy – lung cancer – was tion study in first-line NSCLC, which is due During the earnings call, CSO Lynch not- called into question in a big way with the to complete in the first quarter of 2018 but ed that lung cancer is “unbelievably difficult failure of AstraZeneca PLC’s competing could be reported by the end of the year. to treat” and stressed that the company has CTLA-4/PD-L1 combination in the Phase III CEO Giovanni Caforio started the call by a comprehensive program in lung cancer MYSTIC study. noting the differences in trial design. Check- and “is not wedded to any one approach.” AstraZeneca announced on July 27 that Mate 227 will have a total of 2,220 patients Bristol notes that the two-part CheckMate the combination of its PD-L1 inhibitor Imfinzi compared to 1,100 for MYSTIC. The studies 227 study gives the company the ability and (durvalumab) with the investigational CTLA- tested different drugs – Opdivo is a PD-1 in- optionality to look at multiple combination 4 inhibitor tremelimumab failed to meet hibitor whereas Imfinzi is a PD-L1 inhibitor strategies in different populations. It will test a progression-free survival (PFS) endpoint and there are subtle differences in biological four regimens – Opdivo, Opdivo with Yer- when tested against standard-of-care che- effects associated with these mechanisms voy, Opdivo with chemo and chemo alone motherapy in patients with at least 25% PD- that could have an impact on performance in first-line metastatic NSCLC. L1 expression in the MYSTIC first-line meta- that has not been appreciated yet. “The study is purposefully designed to static non-small cell lung cancer (NSCLC) The difference in this target could result investigate multiple hypotheses across study Furthermore, Imfinzi as a monother- in different results when used in combina- a range of investigational Opdivo-based apy would not have met a secondary PFS tion with a CTLA-4 inhibitor, chief scientific regimens, including Opdivo-plus-Yervoy endpoint in the study, the company said. officer Thomas Lynch suggested. and chemo combinations, with optionality Overall survival (OS) data are due to re- And there were different schedules for around endpoints and patient populations,” port in the first half of 2018 and although dosing, which is very important for the Bristol commented to Scrip. some immuno-oncology drugs have failed PFS and yet were able to meet the more Highlights Of Bristol’s 2Q 2017 Sales important OS endpoint, some analysts are now very pessimistic. PRODUCT 2Q 2017 SALES INCREASE FROM 2Q 2016 Biomedtracker analysts commented in a Opdivo $1.19bn +42% July 27 report that the negative outcome Eliquis $1.176bn +51% in MYSTIC was “surprising and devastating” for Imfinzi and could have rippling effects Yervoy $322m +34% on the view of PD-1 inhibitors generally in Orencia $650m +10% oncology, not just in NSCLC. They also noted Hepatitis C Virus franchise $112m –79%

The company also just started a new Lynch also noted that the company inhibitor Tecentriq (atezolizumab) in sec- Phase III study called CheckMate 9LA testing invested in new CTLA-4 targets, includ- ond-line NSCLC. Opdivo with Yervoy and chemotherapy vs. ing a probody in preclinical development Chief Financial Officer Charles Bancroft chemo alone in the first-line treatment of through a 2014 partnership with CytomX noted continued growth for Opdivo in the Stage IV NSCLC. Therapeutics Inc. US, with a year-over increase of 19%. Bristol said that it hopes that its family of “So we believe that CTLA-4 is an impor- In second-line lung cancer in the US, it studies will demonstrate the best opportu- tant mechanism,” he said. maintained an 40% market share as it exited nity in first-line lung cancer. It’s important to determine the optimal the second quarter. The trends in renal cell way to use the drug and how to improve cancer remained strong with approximately CSO: CTLA-4 IS “IMPORTANT outcomes – the dosing schedule is very im- 50% share, and the company is seeing early MECHANISM” portant, the exec added. signs of acceleration in head and neck can- During the call, the company once again Barclays’ Meacham commented in a note cer, the exec said. reaffirmed its commitment to the CTLA-4 after the call that while there are “legitimate “Given the current trends and strength mechanism. reasons to question the CTLA-4 approach,” of our business in the first half of the year, CTLA-4 is one of only two drug classes in the optionality from CheckMate 227’s mul- we believe that Opdivo will grow in the US immuno-oncology shown to have an im- tiple arms and next-generation follow-ups compared to 2016, despite pressure in the pact on survival, Lynch said. to Yervoy “better hedges the risk of Bristol second half of this year due to the competi- Lynch also noted that the National Com- getting on to the front-line market relative tive dynamics in both first- and second-line prehensive Cancer Network (NCCN) guide- to MYSTIC.” lung cancer,” Bancroft said. lines have endorsed the PD-1/CTLA-4 com- Internationally, sales of Opdivo were up bination in small cell lung cancer and in STRONG QUARTER UNDER 17% sequentially as Bristol continued to mesothelioma and the company has Phase MYSTIC’S SHADOW see adoption across second-line NSCLC and II data showing strong signals in renal cell If it hadn’t been for MYSTIC, the second- renal cancer. Outside oncology, the novel cancer and MSI-high colorectal cancer. quarter earnings call would have been a anticoagulant Eliquis once again delivered Within the next 12 months, large trials will positive occasion, similar to the first-quar- strong sales and the company expects report in NSCLC, renal cell carcinoma, head ter report. Opdivo maintained its position “a significant opportunity for continued and neck cancer and small cell cancer, the despite facing more competition across growth,” Bancroft said. exec said. indications, including from Roche’s PD-L1 Published online 27 July 2017

J&J’s Symtuza Will Debut In Europe On Cramped HIV Market LUCIE ELLIS [email protected]

ohnson & Johnson’s quadruple HIV virus particles. Emtricitabine and tenofovir TOUGH HIV MARKET combination therapy Symtuza has alafenamide are substrates and competitive Michael Haydock, Datamonitor Healthcare Jbeen granted a positive recommenda- inhibitors of HIV reverse transcriptase; after lead analyst for infectious diseases, ex- tion for market approval in Europe – a first phosphorylation, they are incorporated into pects Symtuza to be “mainly positioned in regulatory nod for the product worldwide – the viral DNA chain, resulting in chain ter- treatment-experienced patients where the but competition will be tough. mination. Cobicistat enhances the systemic use of protease-inhibitor based-regimens is Janssen Pharmaceuticals Inc., J&J’s exposure of darunavir and has no direct an- much more common due to their high bar- pharma business, also faces the challenge tiviral effect. riers to resistance.” He told Scrip this strategy of positioning Symtuza on the market in a The European Medicine Agency’s scien- would make sense considering the drug’s way not to cannibalize the company’s HIV tific committee, the CHMP, said in its recom- benefits in patients with resistance to other market share held by Prezcobix (a combina- mendation for approval that the “benefits therapies and because of the growing num- tion of cobicistat and darunavir). with Symtuza are its ability to achieve effec- ber of available HIV therapies in Europe. Symtuza, also known as D/C/F/TAF, is a tive antiretroviral response in a once daily, The HIV treatment market is vast, with fixed-dose combination of four active sub- single pill regimen.” many approved drugs and generic options stances: darunavir, cobicistat, emtricitabine The most common side effects with Sym- available, as well as novel therapies moving and tenofovir alafenamide. It will be avail- tuza use are diarrhea, nausea, fatigue and up through the pipeline. able in Europe as 800 mg, 150 mg, 200 mg rash. The treatment is indicated in Europe However, Janssen told Scrip it was target- and 10 mg film-coated tablets. for the treatment of human immunodefi- ing “naïve and stable patients, which repre- Darunavir inhibits the HIV protease and ciency virus type 1 (HIV-1) infection in adults sents the majority of patients.” prevents the formation of mature infectious and adolescents (aged 12 years). Published online 24 July 2017 scrip.pharmamedtechbi.com 4 August 2017 | 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.

Selected clinical trial developments for the week 21–27 July 2017

LEAD COMPANY/PARTNER COMPOUND INDICATION COMMENTS Phase III Results Published Roche Actemra (tocilizumab) giant cell arteritis GiACTA; NEJM, July 27, 2017. UCB SA/Amgen Inc. Evenity (romosuzumab) osteoporosis The Lancet online, July 26, 2017. Updated Phase III Results bronchiectasis, Linhaliq (ciprofloxacin) ORBIT-3, -4; positive data, pulmonary Aradigm Corp./Grifols SA non-CF with chronic Ps. liposomes exacerbations reduced. aeruginosa lung infection bicetegravir plus emtricit- Gilead Sciences Inc. abine/tenofovir alafenamide, HIV infection Study 1489, 1490; safe and effective. fixed-dose combination Isentress HD (raltegravir) Merck & Co. Inc. HIV infection ONCEMRK; none- inferior to twice daily dosing. once-daily Phase III Interim/Top-line Results Imfinzi (durvalumab) non-small cell lung cancer MYSTIC; missed PFS primary endpoint, AstraZeneca PLC plus tremelimumab (NSCLC) study continues to assess OS . EGF-mutation positive FLAURA; PFS and clinically meaningful AstraZeneca PLC Tagrisso (osimertinib) NSCLC, first-lline benefit found. Symtuza (duranavir/ Gilead Sciences Inc./ EMERALD; positive results for single-tablet cobicistat/ emtricitabine/ HIV infection Johnson & Johnson once-daily regimen . tenofovir alafenamide) dolutegravir vs. lopinavir/ DAWNING; positive results of combo with ViiV Healthcare HIV infection, second-line ritonavir, plus 2 NRTIs dolutegravir. doravirine plus DRIVE-AHEAD; once-daily single tablet met Merck & Co. Inc. lamivudine/tenofovir HIV infection primary endpoint. disoproxil fumarate Exparel (bupivacaine) anesthesia (single dose Pacira Pharmaceuticals Inc. C326, C327; reduced pain score, opioid use. liposome nerve block) Tetraphase Pharmaceuticals Inc. eravacycline intra-abdominal infections IGNITE4; achieved primary endpoint . Habeo cell therapy, adipose Cytori Therapeutics Inc. scleroderma STAR; mixed results. derived head and neck cancer, Merck & Co. Inc. Keytruda (pembrolizumab KEYNOTE-040; failed to improve overall survival . second-line PF-06439535, bevacizumab Pfizer Inc. NSCLC REFLECTIONS; positive results. biosimilar Shionogi & Co. Ltd./Roche S-033188 influenza CAPSTONE 1; positive results. Phase III Initiated adalimumab, biosimilar Boehringer Ingelheim GMBH psoriasis VOLTAIRE-X, versus Humira. (BI695501) Mitsubishi Tanabe Pharma Ingrezza (valbenazine) tardive dyskinesia J-KINECT; to take place in Japan. Corp./ Neurocrine Biosciences Inc. Soligenix Inc. SGX942 (dusquetide) mucositis DOM-INNATE; in cancer patients. International Partnership for dapivirine vaginal ring HIV prevention DREAM; long-label extension, in Africa. Microbicides Inc./Johnson & Johnson ArQule Inc. ARQ 087 biliary tract cancer A multi-kinase inhibitor. Biohaven Pharmaceuticals rimegepant migraine An orally active CGRP antagonist Holding Co. Ltd. Source: Biomedtracker

Will Mitsubishi’s High Offer Price For CNS Target NeuroDerm Deter Others? STEN STOVALL [email protected]

earching to replenish its drug pipeline, offer a solution for almost every Parkinson’s sum-of-the-parts valuation is just above the Japan’s Mitsubishi Tanabe Pharma disease patient, from moderate to the very $39 offer, suggesting the consideration fair- SCorp. has “zeroed in” on NeuroDerm severe stage of the disease. It’s lead drug- ly reflects the Phase III execution, regulatory Ltd.’s promising stable of CNS assets, of- device combination product ND0612 is in - notably drug-device challenges and US fering to buy the Israeli target for $1.1bn in Phase III for Parkinson’s disease and has re- Orphan Drug competition - and commer- cash, a price some analysts think will ensure cently had positive trial data. cial launch risks,” the analysts added. no competing counter-offers materialize. Explaining its reasoning to agree to the A counterbid could possibly be attracted Terms of the transaction, backed unani- sale, NeuroDerm’s CEO Oded Lieberman in from a suitor that has an extremely optimis- mously by NeuroDerm’s board of directors, a statement said Mitsubishi Tanabe Pharma tic view of NeuroDerm, however. is $39 per share in cash, implying an equity “has demonstrated development and com- Jefferies said that a “best case” scenario for value of some $1.1bn and a premium of mercialization expertise in the field of neu- ND0612 would give the Israeli biotech fair 79% over the unaffected price on June 9, rology and we are confident that the com- value of more than $75 per share, represent- 2017 of NeuroDerm’s ordinary shares on the bination of their resources and the robust ing a $2bn valuation for the target compa- NASDAQ stock market before rumors of a data supporting ND0612, our Phase III Par- ny, on the assumption of $1.7bn worldwide possible deal began to circulate, and a 17% kinson’s disease product candidate will help peak sales. premium over the closing stock price on make this important new therapy available Published online 24 July 2017 July 21. Assuming no hiccups, NeuroDerm as broadly and rapidly as possible.” said it expects the takeover transaction to “Given the significant premium offered close in the fourth quarter. and existing shareholder agreements, we CLICK NeuroDerm’s key focus is on Parkinson’s regard a counterbid to perhaps be unlikely,” Read full story at: disease, where it has three clinical-stage analysts at Jefferies said in a reaction note. http://bit.ly/2vfqhlk product candidates in development which “Our $42 per share NPV [net present value]

APPOINTMENTS

Geoffrey Kim has been appointed head Merrimack Pharmaceuticals Inc. has able formulations of leuprolide, and an of oncology strategic combinations at As- named Thomas Needham as chief busi- oral MMP-12 inhibitor for inflammatory traZeneca PLC, and Jean-Charles Soria ness officer, designing and implementing and fibrotic diseases. has joined MedImmune LLC as senior the company’s strategy for its pipeline of vice president, head of oncology innovative clinical and preclinical assets. Needham Mike Owen has been appointed to the medicines. Kim was most recently director, was most recently senior vice president of board of the antibody-drug conjugate division of oncology products, at the US business development at C4 Therapeutics, company, Glythera, as a non-executive di- FDA’s office of hematology oncology prod- responsible for executing business devel- rector. Owen is a director of several compa- ucts, and will focus on the development of opment strategy and corporate partner- nies including GammaDelta Therapeutics, AstraZeneca’s late-stage immuno-oncology ships, and before that was a managing ReNeuron plc and Zealand Pharma A/S, combinations program. Soria was previously director at Synthesis Capital. and was previously Chief Scientific Officer professor of medicine and medical oncology at Kymab. He left GlaxoSmithKline in 2010 at France’s South-Paris University, and will Taipei, Taiwan-based Foresee Pharma- where he was senior vice president and lead a team responsible for the early oncol- ceuticals Co. Ltd.,has appointed Law- global head of research of the biopharma- ogy biologics portfolio at MedImmune. Both rence Gan to the position of CEO. He will ceuticals R&D unit. will be based in Gaithersburg, Maryland. work closely with founder and executive chairman Ben Chien to ensure a seamless PTC Therapeutics Inc. has promoted Biogen has appointed Alisha Alaimo transition of responsibilities. Gan was for- Joseph McIntosh to senior vice president senior vice president of its US therapeu- merly president and CEO of the Develop- and head of clinical development, respon- tic operations, reporting to CEO Michel ment Center for biotechnology in Taipei, sible for all aspects of clinical development Vounatsos and focusing on its multiple and before that was a senior director at across the company’s portfolio. McIntosh sclerosis and spinal muscular atrophy ther- Biogen Inc., director of drug discovery at was previously vice president of clinical apies. Alaimo joins from Novartis, where Boehringer Ingelheim, and senior direc- development, where he was the lead cli- she was vice president and head of its car- tor at Millennium Pharmaceuticals Inc. nician within the development group, fo- diovascular business unit. Foresee is developing stabilized inject- cused on rare diseases.

scrip.pharmamedtechbi.com 4 August 2017 | Scrip intelligence | 23 2017

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