Does Novartis Need a Big Immuno- Oncology Deal?
Sandoz’s Biosimilar Rejection Ups Key Clinical Data And Drug Expert View Risks, But Won’t Kill Market Approvals Expected New data on growth in China’s FDA’s rejection of Sandoz’s version of In 2H 2016 Scrip takes a look at some turbulent pharma sector paint a Amgen’s Neulasta has revealed the truth clinical trial read-outs and drug approvals mixed and complex picture, indicating that chasing the biosimilar market may expected, clinical trials due to report in both challenges and opportunities be riskier & more costly (p3) the second half of the year (p18) ahead (p20)
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Scripscripintelligence.com Pharma intelligence | informa space given what’s coming.” The company has previously stressed that its leadership position in chimeric antigen receptor T-cell therapy (CAR-Ts) will get it back in the thick of it. “I believe that we have a very strong self-generated, through in-licensing and through acquisition, early-stage immuno- oncology pipeline,” he said. And, he reiterat- ed the common refrain in the industry that success in the field will be determined over the long-term through the development of combinations. In May, Novartis announced a restructur- ing to break Novartis Oncology out into a separate business unit led by its own CEO, Bruno Strigini, who will report directly to Joseph Jimenez Jimenez. Merck & Co. Inc., Bristol and Roche have already launched the first immune check- point inhibitors, the PD-1/L1 inhibitors Key- Does Novartis Need A Big Immuno- truda (pembrolizumab), Opdivo (nivolumab) and Tecentriq (atezolizumab), respectively, while many others are in mid- to late-stage Oncology Deal? Jimenez Says No clinical development by drug makers like JESSICA MERRILL [email protected] AstraZeneca and Pfizer Inc. Novartis, which has been the number The oncology player missed out on the first The chief executive was pressed by ana- two oncology player in the world behind round of immune checkpoint inhibition lysts on two occasions during the compa- Roche, largely riding on the success of the and now some investors are wondering if ny’s second quarter sales and earnings call blood cancer blockbuster Gleevec (ima- the pharma needs to buy a rival to catch July 19 about whether or not Novartis needs tinib), is now trying to catch up in immuno- to complete an expensive acquisition, or up. During the company’s second quarter oncology at the same time Gleevec is fac- even consider buying an immuno-oncol- ing generic competition for the first time. sales call CEO Jimenez insisted Novartis ogy leader like Bristol-Myers Squibb Co. or The company’s other big cancer drug is the has the internal expertise to execute. AstraZeneca PLC to remain competitive in Gleevec follow-on Tasigna, which gener- oncology. ated $458m in sales in the second quarter, ovartis AG CEO Joseph Jimenez is Jimenez largely side-stepped the mega- up 15% despite the availability of generic maintaining that the Swiss pharma merger question by responding that he imatinib beginning in February. Nhas the internal expertise to execute wouldn’t speculate on what the company With its expertise in blood cancer, No- on its oncology strategy, despite having might do next in immuno-oncology. How- vartis bought quickly into CAR-T immuno- fallen behind rivals in the competitive field ever, he added, “I don’t feel like we have to therapy technology through a 2012 deal of immuno-oncology. do something in the immuno-oncology CONTINUED ON PAGE 8
BROUGHT TO YOU BY THE EDITORS OF PHARMASIA NEWS, START-UP AND SCRIP INTELLIGENCE IN THIS ISSUE J&J reports strong 2Q earnings and executives talk about While FDA supported approval strategy for defending against biosimilar competition in the US of brodalumab, several recommended a black box warning
FDA approval of Valeant’s Relistor will pit the franchise against Movantik 9 11 13
COVER / Does Novartis Need A Big Immuno-Oncology Deal? from the editor Jimenez Says No [email protected] 3 Sandoz’s Biosimilar Rejection Ups Risks, But Won’t Kill Market The fully diversified big pharma corporation is a 4 Novo’s CSO Has A Lifetime Product Plan For business model that has been falling out of favor Diabetes Patients for years now. Lucie Ellis’s interview with Novo Nor- disk CSO Mads Krogsgaard Thomsen on page 4 7 Roche Sees Cancer Combos Start To Deliver highlights the risks of going too far the other way, though: specializing in one area has its own chal- 9 Valeant’s Oral Relistor Poised To Face-Off Against lenges, and not just because all your eggs are at risk AstraZeneca’s Movantik if something bumps your basket. You also have to 10 Emerging Diseases: Disruptive, Commercially Risky, worry about being your own worst enemy when it But GSK Has A Solution comes to competing on the market. Meanwhile, it’s results season, which is a tempt- 11 J&J Thinks It Can Win Over Biosimilar Competition ing time to bury bad news. Novartis was first to re- 12 Policy & Regulation Briefs port its financials (see cover story), and sure enough it had a couple of awkward revelations tucked un- 13 Suicide Warnings For Valeant’s Siliq Could Hinder Access To Psoriasis Treatment obtrusively into its 12-page announcement. It is understandable that a firm might be reticent about 14 Business Bulletin the fact that one of its US biosimilars had received 15 Changes Brewing At Bayer, But Pharma Strategy an FDA knockback (p3), or that it had flunked an Remains On Point inspection by the UK medicines regulator. Less obvi- ous is why it wouldn’t want to crow about its much- 16 Merck Singapore R&D Collab Looks To Get Peptides vaunted CAR-T program, which failed to make the Into Cells cut in a list of future blockbusters. 17 R&D Bites 18 Key Clinical Data And Drug Approvals Expected In 2H 2016
20 Expert View: Bounce Or More Bumps? New China Market exclusive online content Data Offer Bit Of Both 21 Stockwatch: Earnings Season Appears Not At Home Deal Watch: Galenica Offers For Relypsa, But Other To Brexit Suitors May Emerge 22 Pipeline Watch Allergan backs out of deal with Adamis for an EpiPen competitor just two months after signing the licensing deal, but before an up-front 23 Appointments payment due date kicks in. AbCellera to team with MassBiologics to discover antibodies against drug-resistant Klebsiella infections. http://bit.ly/2a5GzVI
Where Is The Patient Voice In Alzheimer’s Disease Drug Development? Companies developing treatments for Alzheimer’s disease and other types of dementia are failing to incorporate the patient voice in their drug development plans, said Marc Wortmann, Executive Director, Alzheimer’s Disease International, in an interview with Scrip. @scripnews /scripintelligence http://bit.ly/2a942QT
/scripintelligence /scripintelligence
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Sandoz’s Biosimilar Rejection Ups Risks, But Won’t Kill Market DONNA YOUNG [email protected]
The FDA’s rejection of Sandoz Inc.’s version of Amgen’s Neulasta Apotex’s application for its filgrastim biosimilar, which the com- (pegfilgrastim) has revealed the hard truth that chasing the bio- pany said in February 2015 was officially under review by the FDA, similar market may be a riskier and more costly endeavor than also likely has been turned away. The firm, however, has remained companies anticipated. mum on the matter and as a private company, doesn’t have to dis- close that information. andoz Inc. has appeared to be on easy street with its US biosim- ilars – being the first company to enter the US market last year, GREATER RISK Swhile another of its applications last week breezed through an But with Novartis confirming Sandoz’s US pegfilgrastim application FDA advisory committee meeting. had been declined, the risk for all biosimilar companies has just gone But stark reality came knocking: Sandoz was hit with a complete up – a concern that may have some firms contemplating backing response letter (CRL) for its version of Amgen Inc.’s long-acting away over worries they may have to work harder and expend more granulocyte colony-stimulating factor (G-CSF) Neulasta (pegfilgras- resources to bring a product to the US market, Fuhr said. tim) – reminding the biosimilar community that as much as some After all, he said, if the economics don’t add up and it looks like US regulators have appeared to be cheerleaders in recent months, biosimilar manufacturers may not get a good return on their invest- the agency won’t pull its punches if it decides a product isn’t ready ment, why go down that road, especially where there’s now even for prime time. more uncertainty –drug makers’ greatest fear. But, said Joseph Fuhr, professor of economics at Widener University, “These companies are going to look at this as another barrier to it’s also a reminder biosimilars is an emerging market in the US and market entry,” Fuhr said. “things like that happen along the way when you have a new industry.” He noted biosimilar makers already are contending with the 180- Nonetheless, Fuhr said the FDA’s rejection of Sandoz’s biosimilar day notice of commercial marketing a panel at the US Court of Ap- application brings home the hard truth it may be a riskier and more peals recently ruled was mandatory for all applicants, meaning it costly endeavor than companies anticipated. will be at least six months after approval before those firms can start bringing in cash from their products. BURYING BAD NEWS Sandoz’s parent company Novartis AG disclosed the news it had re- MARKET SURVIVAL ceived the CRL from the FDA for the pegfilgrastim biosimilar candi- But Fuhr said he wasn’t completely discouraged on the news over date by embedding a brief statement in its July 19 second-quarter Sandoz’s pegfilgrastim application being refused by the FDA. earnings report. “I still believe the biosimilar market will develop because there’s a Vasant Narasimhan, chief medical officer and head of drug devel- lot of potential cost savings there,” he said. opment at Novartis, revealed during a conference call with inves- Fuhr said he expected prices for biosimilars to reach discounts of tors and analysts that rejection actually came at the end of June. up to 50% to the innovators’ costs in the next five to six years, which But he provided little else. will help drive acceptance of the products sooner by prescribers “These are obviously complex filings where we have different ele- and patients, despite the current skepticism. ments we need to work through,” Narasimhan said. “I don’t think we’re He acknowledged, however, the timeline for how quickly biosim- ready to discuss the details of the response because we still need to ilars’ prices fall will be dependent on several variables, most notably, work through with the agency how best to resolve their concerns.” how quickly other competitors enter the US market. He emphasized that until Sandoz submits a data package to the The FDA said there’s about 60 candidates based on about 20 in- FDA, it’s difficult to know how the agency may classify the response novator products in the agency’s biosimilars development program. and the overall timeline for an action. But only six companies have disclosed nine applications in the US, Sandoz made history last year with Zarxio (filgrastim-sndz), a ver- two of which have been approved: Zarxio and Pfizer’s and Celltrion sion of Amgen’s G-CSF Neupogen, as the first biosimilar licensed Inc.’s Inflectra (infliximab-dyyb), a version of Johnson & Johnson’s in the US. Remicade. But it wasn’t the first known company to get a CRL for a biosimi- So it’s currently unclear which innovators’ products are being lar. That title went to Pfizer Inc., which also buried the news in its pursued by biosimilars makers, although Amgen’s drugs have been Oct. 27, 2015 earnings report the FDA had snubbed the company’s the most known to be targeted. epoetin alfa biosimilar, a version of Amgen’s Epogen. But Fuhr warned that too many competitors chasing the same There’s speculation the FDA likely has rejected Apotex’s peg- brand-name biologic could be a problem for the sustainability of filgrastim biosimilar, given the Canadian firm disclosed in De- the US biosimilar market, especially if prices drop too low, creating cember 2014 its application had been accepted by the US regu- a disincentive that may drive some companies out of the space. latory agency. Published online 07-19-2016
scripintelligence.com 29 July 2016 | Scrip intelligence | 3 HEADLINE NEWS
Novo’s CSO Has A Lifetime Product Plan For Diabetes Patients Novo Nordisk’s executive vice president and chief scientific officer, Dr. Mads Krogsgaard Thomsen, talks to Scrip about the Danish firm’s biggest challenges as a leader in the development of diabetes therapies – including the positioning of its numerous marketed type 2 diabetes therapies and how the company can stay innovative in a saturated disease space.
LUCIE ELLIS [email protected]
ovo Nordisk AS’s biggest dilemma, according to chief scientific officer NMads Krogsgaard Thomsen, is how the company can position all of its diabetes products in the market to avoid cannibaliza- tion of the drugs and to ensure patients get the benefit of the best-suited treatment for their diabetes. “We have a multitude of products for the same disease,” Krogsgaard Thomsen told Scrip in a recent exclusive interview follow- ing the company’s flagship presentation of new cardiovascular outcomes data for GLP1 therapy Victoza (liraglutide) at the American Diabetes Association’s scientific sessions last month. “This is unusual,” Krogsgaard Thomsen said, “It hasn’t been seen before, as I recall, that a single company has this many new offerings for the same disease all at once. because of all the benefits – such as fewer tophy (previously known as IDegLira), It does cause a dilemma.” However, Novo’s hospitalizations and fewer hypoglycemic a combination of Tresiba and Victoza. CSO said the company has given a lot of events,” Krogsgaard Thomsen said. Novo also has a meal time insulin offer- thought to the structure for these products He added that Victoza is easy for patients ing, NovoRapid for progressed disease; and how they should be best used by doc- to use because it doesn’t need to be titrat- and an injectable liraglutide product tors to reach the right patients at the right ed like insulin and the same dose is given Saxenda, which is indicated as an ad- stage of their disease. junct to a reduced-calorie diet and increased physical activity for weight ‘We have a greater offering than the other diabetes management in pre-diabetics or type 2 diabetes patients. drug developers, so we had to think smartly about “We have a greater offering than the oth- er diabetes drug developers, so we had to how to make it simple for doctors to understand think smartly about how to make it simple when and how to use our products’ for doctors to understand when and how to use our products,” Krogsgaard Thomsen said. “There will be cannibalization of some every day. Krogsgaard Thomsen places Vic- products but this is avoided to the greatest Victoza, the current market-leading non- toza, and its follow-on product semaglu- possible extent.” insulin type 2 diabetes therapy, is easy to tide, as early use options for treating type 2 place according to Krogsgaard Thomsen diabetics. The next step in Novo’s diabetes THE NEXT WAVE because of its potential beneficial effects Diabetes is a well-served patient population on cardiovascular (CV) and kidney disease therapy hierarchy would be a ultra-long- and the sector has seen great advances in – the biggest healthcare cost burdens acting basal insulin, such as its product the last decade – so what else can compa- associated with type 2 diabetes. “Even Tresiba (insulin degludec), to better man- nies like Novo come up with? According to though insulin is a cheaper option for type age patients’ glycemic levels when their Krogsgaard Thomsen, “There is not an easy 2 diabetes treatment, healthcare costs have disease has progressed. answer.” However, he highlighted that the been proven to be reduced when you use Finally, Krogsgaard Thomsen suggests a glucagon-like peptide-1 [GLP1] product use of combination therapy such as Xul- CONTINUED ON PAGE 6
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8.4m Thanks to new drugs, by
1/3 2027 decrease the global HCV patient base is expected to 2.7m 1 decrease to one-third of what it is today. 2016 2027
MORE ROOM TO GROW Hepatitis C
Hepatitis C has seen a paradigm shift in treatment in the past ve years. The market has grown exponentially – but there’s still room to grow as next-generation therapies reach the market.
FDA Approval1, 2
G 2011 2016 G Merck Victrelis L May G
48 weeks of 12 weeks or less 2011 G Vertex Incivek treatment with of treatment, G
G troublesome side e ects safe oral regimen
G G ~50% ≥90% G G Johnson chance of being cured chance of being cured L Nov G
L & Johnson Dec 2013 Gilead Sovaldi G Olysio 2013 G
G G $ 2 G 2011 Global sales of G HCV drugs pre-DAA $3.3bn G
G
G 2015 Global sales peaked at
G
L 2 Oct G
Gilead Harvoni 2014 G $23.7bn L G Dec AbbVie
G 2014 Viekira Pak Bristol-Myers G Squibb G G HCV sales expected to begin to plateau in 2016, and Daklinza July L G remain for next ve years around 1
2015 G AbbVie G $20bn Technivie G 25 billion L Jan Merck G
G 2016 Zepatier
G 20 billion
G June L Gilead Epclusa G 2016 15 billion 2015 2016 2017 2018 2019 2020 Go to scripintelligence.com for more data on Hepatitis C Source: 1DataMonitor Healthcare, sales totals for 2016 and beyond are based on DataMonitor Healthcare projections; 2Morningstar; 3Trio Health
scripintelligence.com 29 July 2016 | Scrip intelligence | 5 HEADLINE NEWS
CONTINUED FROM PAGE 4 of combination treatments – particularly challenge with diabetes treatments is pa- the devices required to deliver the treat- Positive Tagrisso tients becoming “immune” to therapies over ments to diabetes patients. Data Boost AZ time. “There is a lot to do still, “Krogsgaard Krogsgaard Thomsen said this chal- Thomsen said, “because even semaglutide lenge would be combatted by the AstraZeneca’s Phase III AURA3 trial has over time will probably start failing – you company completing “rigorous trials” met its primary endpoint, demonstrat- need something that can be added to that that look past endpoints of just glucose ing better progression-free survival drug. This will have to be a new mechanism control. “We are moving away from the (PFS) compared to standard platinum- though because I don’t think we can ever question of blood sugar to look at actu- based doublet chemotherapy. The make a better GLP1 than semaglutide.” ally being able to make a real change to a AURA3 randomized trial assessed the patient’s life – in terms of life expectancy, efficacy and safety of Tagrisso (osimerti- cardiac outcomes and more,” he said. nib) as a second-line treatment in more Novo Nordisk will “Novo Nordisk will have to do very so- than 400 patients with EGFR T790M have to do very phisticated trials that look at more end- mutation-positive, locally-advanced or points, specifically more hard endpoints, metastatic NSCLC, whose disease had sophisticated trials that than we have done in the past.” In these progressed following first-line EGFR more sophisticated studies Krogsgaard tyrosine kinase inhibitor (TKI) therapy. look at more endpoints Thomsen said it will be easier for the Tagrisso also demonstrated a safety pro- company to determine health economic file consistent with previous trials. For Novo’s next wave of diabetes in- benefits for new therapies, in turn mak- “[This data] means that AstraZeneca novation, the company is in the early ing it easier for the company to convince can now move to file for full approval stages of development for a triple action regulators and payers of a potential new of this treatment in the US and Europe combination drug, using semaglutide, drug’s wider benefit. where we had previously been granted its Victoza follow-on, as the scaffolding. accelerated/conditional approvals, “We are exploring more activities, such as TYPE 1 DIABETES respectively, on the strength of early data,” an AstraZeneca spokesperson weight loss, that cannot be achieved by In the type 1 diabetes setting Novo also told Scrip. “Moving to full approval is one target but can be achieved by two has some early pipeline studies ongoing, a high priority for AstraZeneca. Once or more – potentially even in the same including trials for Victoza use in early- we achieve this, many more patients in molecule,” Krogsgaard Thomsen said. onset diabetics – enrolling patients who need will be able to access Tagrisso as a There are challenges for these triple- have been diagnosed with type 1 diabe- new standard of care. Also, future Phase plus combination treatments though tes in the last three months. The aim of III studies by other companies working this study is to try and preserve any beta that Novo is hoping to overcome. “They in this area will need to go head-to-head cells that are still alive in the pancreas. can be dangerous, they can be immu- with Tagrisso to demonstrate their Novo is also exploring stem cell therapy nogenic – the more you have built into superiority in this patient group.” options for type 1 diabetics. The company the molecule, the more changes you are According to AstraZeneca, EGFR mu- has been conducting embryonic stem making, the more likely it is to trigger tations occur in approximately 10-15% cell research in this area since the 90s but the immune system into creating anti- of NSCLC patients in Europe and the Krogsgaard Thomsen said it has been less bodies,” Krogsgaard Thomsen noted. He US, and 30-40% of NSCLC patients in vocal about this until recently. The compa- added it is his aim is to keep the com- Asia. “Nearly two-thirds of patients with ny is also interested in the development of pany focused on human proteins where NSCLC who are EGFR mutation-posi- possible. Krogsgaard Thomsen cited is- a bionic or artificial pancreas. Krogsgaard tive and experience disease progression sues with Sanofi’s combination therapy Thomsen told Scrip he’d loved to help cre- after being treated with an EGFR-TKI iGlarLixi (or LixiLan as it was previously ate an intelligent diabetes pump linked to develop the T790M resistance mutation. a smart phone to regulate glucagon and known) – and concerns about patients These patients may be eligible for treat- insulin levels on a real-time basis. in trials developing antibodies to the ment with Tagrisso,” added the spokes- While Novo’s CSO is confident the com- drug. The protein in iGlarlixi is Exendin-4, person. In addition to PFS, the objective pany can run its diabetes drug business originally found in the venom of Gila response rate, disease control rate and alone, he said the group would be inter- monster lizards. “There was a lot of dis- duration of response also achieved ested in technology partnerships for the cussion about biology and the outcome clinically meaningful improvement development of smart insulin pumps and for iGlarLixi; I fear Novo Nordisk – which versus chemotherapy. A full evaluation other technology-led projects. is very preoccupied by human nature of of AURA3 data, including an analysis of Published online 07-18-2016 our molecules – is moving from human overall survival, is ongoing, and results to less human. I’m not saying we will go will be presented at an upcoming medi- there but it is a concern of mine.” View table showing branded cal meeting, said the firm. type 2 diabetes therapies by Later down the line, as has already [email protected] 2015 sales here: been seen with products from both Published online 07-18-2016 http://bit.ly/2a07KMB Novo and Sanofi, regulators can be wary Read full story at: http://bit.ly/2aM9Ct7
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Roche Sees Cancer Combos Start Zafgen Drops Beloranib To Deliver Restructuring and refocusing are pretty Roche presented a strong second quarter and was able to highlight a positive much dirty words to biotech inves- debut of Tecentriq, its PD-L1 antagonist, which brought the Swiss group into tors. That held true when Zafgen Inc. the lauded programed-death checkpoint inhibitor field. announced both those things after the market close on July 19, pushing the SUKAINA VIRJI [email protected] stock down more than 40%. Zafgen is cutting 34% of its employees oche said group sales increased 5% GOYA results, expected later this year, will and ditching development of its belea- to CHF25bn in the six months to June be the last piece of the puzzle in showing guered obesity drug beloranib in favor 30, slightly ahead of expectations. Net Gazyva’s superiority over Rituxan. R of a barely-in-the-clinic next-gen version. income rose by 3% at constant currencies to Another “pillar” to Roche’s strategy to While the company tried to paint CHF5.5bn. Pharmaceutical sales were up by combat the threat of biosimilars is the the news in a positive light, a staff 4% to CHF19.5bn, driven by oncology and development of subcutaneous versions reduction and abandoning of its lead immunology drugs. of older drugs Herceptin and MabThera. program were hard pills for investors Tecentriq (atezolizumab), which was ap- These are selling well, said O’Day. to swallow. proved by the FDA in May 2016 for bladder Will converting the market to subcutane- Beloranib is a MetAP2 inhibitor cancer, had revenues of CHF19m “in a little ous Rituxan make it difficult to roll out the that Zafgen has been studying in a less than a month and a half, representing IV administered Gazyva? No, Roche believes rare genetic disease called Prader- some good underlying demand for Tecen- that clinical data will trump convenience. Willi Syndrome (PWS), which is triq,” said COO Daniel O’Day in a conference Interest is also focused on the Basel- characterized by an insatiable hunger call accompanying the results. based group’s succession plans for the and often leads to morbid obesity. HER2 franchise, in particular new drugs Beloranib was meant to reduce this We are in the process Perjeta (pertuzumab) and Kadcyla (ado- hunger and help control blood trastuzumab emtansine), the antibody- glucose levels. Zafgen was initially of launching five new drug conjugate version of Herceptin studying the drug for wider obesity- molecule entities within (trastuzumab). related indications until safety sig- CFO Alan Hippe is confident about nals pushed the company to pursue the short timeframe of Roche’s HER2 franchise “because here, at the rare disease track. The drug has least in the mid-term, we’re talking about shown strong efficacy signals, but only one year Perjeta, we’re talking about Kadcyla in two deaths in a recent mid-stage combination with Herceptin in chemo- study due to pulmonary embolism Roche is facing the loss of revenue from therapy, and we know those levers.” brought an FDA clinical hold down some of its aging drugs, including cancer Data from the Phase III APHINITY trial, on the company in December 2015. therapies Rituxan/MabThera (rituximab) looking at Perjeta in the neoadjuvant set- Zafgen has been slowly trickling and Avastin (bevacizumab), which are tar- ting, are expected either late this year or out data ever since with promises to gets for biosimilar competition. early next year. “If APHINITY is positive, and investors that strong efficacy results “We are facing biosimilar entry next year we’re encouraged by the new adjuvant re- could help make its case with FDA. Yet, and accordingly we want to maximize the sults in the other data we see, I feel quite on July 19 Zafgen executives released potential of the opportunities we have,” confident that we will grow through the a statement saying the company had finally gotten the promised meeting said CEO Severin Schwan. “We are in the biosimilar erosion curve of Herceptin.” with the regulatory agency and “that process of launching five new molecular Roche is planning to build a broad net- the obstacles, costs and development entities within the short timeframe of only work of combination therapies around timelines to obtain marketing approval one year. This is really unprecedented in Tecentriq. In fact, of the 50 studies Roche for beloranib are too great to justify ad- the history of Roche and it comes at the has ongoing, more than 30 are combina- tion trials. ditional investment in the program.” right time.” Roche confirmed its outlook for this year, The Type A meeting with FDA in- The recent early termination of the GAL- and still expects sales to grow in the low- cluded “a complete data package and LIUM trial of Gazyva (obinutuzumab), due to-mid single digits at constant exchange a well-considered proposal for a path to the successor anti-CD20 product show- rates, and for core earnings per share to forward,” said CEO Tom Hughes in a ing superiority over Rituxan-based regi- grow ahead of sales. Roche continues to call with analysts. mens in first-line follicular lymphoma, has expect to increase its dividend, which was [email protected] helped position Gazyva as the new stan- CHF8.10 in 2015. Published online 07-20-2016 dard of care, and the firm anticipates the Published online 07-21-2016 Read full story at: http://bit.ly/2alTgdz
scripintelligence.com 29 July 2016 | Scrip intelligence | 7 HEADLINE NEWS
CONTINUED FROM COVER Progressing 11 Potential Blockbusters In Innovative Medicine with the University of Pennsylvania, but the EXPECTED company missed out on the early excite- MOLECULE INDICATION MECHANISM OF ACTION PIVOTAL DATA ment around immune checkpoint inhibi- HR+HER2- breast tion, an area of research focused initially on LEE011 (ribociclib) CDK4/6 inhibitor Reported cancer solid tumors. Novartis gained a PD-1 inhibitor in 2014 OAP030 (Fovista) Neovascular AMD Aptamer Anti-PDGF Q42016 Prophylaxis of CGRP receptor through the acquisition of CoStim Phar- AMG 3342 H2 2016 maceuticals Inc. The company presented migraine antagonist Relaxin receptor Phase I data on the PD-1 blocker, PDR001, at RLX030 (serelaxin) Acute heart failure H12017 the American Society for Clinical Oncology agonist meeting in June in advanced solid tumors. RTH258 (brolucizumab) Neovascular AMD Anti-VEGF H12017 But with so many PD-1/L1 inhibitors in ACZ885 (Ilaris) CV risk reduction Anti-IL 1beta 2017 development with what thus far appears to Non-radiographic AIN457 (Cosentyx) Anti-IL17A 2018 be minimal differentiation between them, axial SpA most investors are underwhelmed by the QVM149 (indacaterol/ asthma LABA/LAMA/ICS 2018 late-to-market opportunity. glycopyrronium/mometasome Jimenez indicated that Novartis needs the Heart failure – LCZ696 (Entresto) ARNI 2019 PD-1 as a backbone to compete in the com- preserved EF bination market. “The winners in immuno- QAW039 (fevipiprant) Asthma CRTh2 antagonist 2019 oncology long term are going to win through Relapsing multiple combination therapies and you better have OMB157 (ofatumumab) Anti-CD20 2019 sclerosis a broad line of those combination therapies to capture the economics of what is going Source: Novartis second quarter earnings presentation, July 29, 2016 to become a capitation model in oncology that this will have a really important place expect Entresto will generate $200m in sales going forward with combination therapies,” in cancer care, so no change in our outlook this year and will reach its long-term block- he said. “We see the checkpoint inhibitors or confidence in CTL019,” chief medical offi- buster potential. as table stakes to supplement what is a very cer Vas Narasimhan responded when asked Sales are expected to pick up now that the strong second generation.” about the omission. American College of Cardiology, the Ameri- Novartis will invest about A safety issue emerged with Juno’s can Heart Association and the European lead product JCAR017, which was put on Society of Cardiology all recommended in $200m in the second half a clinical hold by FDA July 7 but the issue May that Entresto should replace angio- was quickly resolved and the trial was tensin-converting enzyme (ACE) inhibitors of the year behind the allowed to continue. The class of drugs and angiotensin receptor blockers (ARBs) in launch of Entresto, largely has shown some impressive clinical trial patients with adequate blood pressure and results in certain B-cell malignancies, but drug tolerance. to build out a primary care there are also a lot of questions about As a result of the positive update to sales force. the medicines, including the manufac- guidelines, the company said it decided to turing process and if the drugs will work increase investment behind Entresto earlier in solid tumors. than expected, largely to build out a primary care sales force and recruit additional medi- CAR-T CTL019 DOESN’T MAKE KEEPING TABS ON ENTRESTO cal support. The company said it would NOVARTIS’ BLOCKBUSTER LIST Outside of oncology, investors are closely spend about $200m more on the effort, As for the company’s leading CAR-T pro- tracking the launches of the heart failure which could reduce operating income to a gram, CTL019, Novartis is in a tight race with drug Entresto (valsartan/sacubitril) and low-single digit decline in 2016 versus 2015. Juno Therapeutics Inc. and Kite Pharma Inc. Cosentyx (secukinumab) for psoriasis, both The company’s Innovative Medicines to be the first to market with the therapy. of which launched last year and are im- (previously Pharmaceutical) division gen- Novartis expects to file CTL019 with FDA in portant future growth drivers for Novartis. erated $8.4bn in sales in the second quar- pediatric acute lymphoblastic leukemia in Cosentyx has been off to a strong launch ter, a decline of 3% over the prior year early 2017. But interestingly, Novartis didn’t and is on track to be one of the company’s period, Novartis reported. Volume growth include the drug on a slide presented to best launches ever, but uptake of Entresto increased 6% but was offset by generic investors on the call of “11 potential block- has been slow, largely because of market ac- competition and negative pricing impact, busters in innovative medicines.” cess issues. largely around Gleevec. Growth products Analysts wanted to know why, and man- Cosentyx generated sales of $260m in the grew 23% to $3.8bn, representing 45% of agement didn’t’ answer directly. “We contin- second quarter, while Entresto generated division sales, the company said. ue to believe in this technology and believe just $32m. But Novartis said it continues to Published online 07-19-2016
8 | Scrip intelligence | 29 July 2016 © Informa UK Ltd 2016 HEADLINE NEWS
Valeant’s Oral Relistor Poised To Face-Off Against AstraZeneca’s Movantik FDA approval of the first oral form of Valeant’s mu-opioid receptor antagonist Relistor will pit the franchise against Movantik for the treatment of patients with opioid-induced constipation with non-cancer pain. JESSICA MERRILL [email protected]
aleant Pharmaceuticals International sition at the time as an opportunity to es- first quarter, according to Evercore ISI ana- Inc.’s new oral version of the mu- tablish a new therapeutic vertical in gas- lyst Umer Raffat. V opioid receptor antagonist Relistor trointestinal disease through Relistor and Valeant said it plans to launch the oral (methylnaltrexone) was approved by FDA primarily Xifaxan (rifaximin), which was ap- formulation in the third quarter and did for the treatment of opioid-induced con- proved for irritable bowel syndrome in 2015 not provide any information on potential stipation (OIC) in adults with chronic non- shortly after the acquisition. pricing or how the price might compare to cancer pain, pitting the franchise against The more convenient oral version of Rel- the subcutaneous formulation. Movantik AstraZeneca PLC’s similar product Movantik istor will be better positioned to compete is priced at a wholesale acquisition cost of (naloxegol). against Movantik, which was the first oral $9.60 per tablet and labeling recommends dosing once daily. Valeant hasn’t had time to share launch plans with investors, given that the com- pany’s new CEO Joseph Papa is focused on stabilizing the company, which has seen its value drop about 90% in the last year around investigations into its pricing and accounting strategies. But the former management had talked about the drug’s ability to act quickly. The sNDA approval was based on the results of a randomized, double-blind Phase III trial comparing once-daily dosing of 450 mg of methylnaltrexone to placebo. Treat- ment demonstrated statistically significant improvements in rescue-free bowel move- ment (RFBM) within four hours of adminis- Shutterstock: Dima Sobko Shutterstock: tration over 28 days of dosing compared to placebo, the primary endpoint of the study. Valeant announced the approval of its mu-opioid receptor antagonist approved Efficacy of oral methylnaltrexone was com- supplemental New Drug Application July for the treatment of OIC in adults with non- parable to that reported in clinical studies 19 after market close, the same day FDA’s cancer pain. The drug was approved in for the subcutaneous product and safety Dermatologic and Ophthalmic Drugs Ad- September 2014, but the launch was held was comparable to placebo. visory Committee recommended approval up by scheduling by the Drug Enforcement Analyst expectations for the Relistor fran- of the company’s Siliq (brodalumab) for Agency. It was ultimately descheduled chise vary. BMO Capital Markets analyst Gary plaque psoriasis. by the DEA in January 2015 and launched Nachman was cautious. “We believe this It was a day of good news for troubled shortly after. market has become more challenging with Valeant, although both drugs are poised to AstraZeneca partnered with Daiichi pressure from payers, less opioid writing enter competitive categories. Sankyo Co. Ltd. to commercialize the drug and AstraZeneca’s aggressive promotion of Relistor has been on the market in 8 mg in the US, with Daiichi agreeing to pay Movantik,” he said in a July 19 research note. and 12 mg subcutaneous formulations for $200m upfront plus $625m in milestone He forecast sales of the combined franchise many years. It was approved in 2008 for the payments under the terms of the deal. will be $83m in 2016 and $158m in 2020. treatment of OIC in adults with advanced ill- While Movantik has a sizeable lead in the On the other end of the spectrum, Rod- ness who are receiving palliative care and in market over oral Relistor, sales of the drug man & Renshaw analyst Raghuram Selvaraju 2014 for the treatment of OIC in adults with have thus far been modest. Movantik gen- speculated the oral formulation would posi- chronic non-cancer pain. erated $17m in sales in the first quarter of tion Reslistor to become a blockbuster con- Valeant gained Relistor through the ac- the year, AstraZeneca reported. The sub- tender. Evercore Isi analyst Umer Raffat mod- quisition of Salix Pharmaceuticals Ltd. for cutaneous version of Relistor generated eled peak sales of $250m for the franchise. $11bn in 2015. Valeant viewed the acqui- about the same amount of sales in the Published online 07-20-2016 scripintelligence.com 29 July 2016 | Scrip intelligence | 9 HEADLINE NEWS
Emerging Diseases: Disruptive, Commercially Risky, But GSK Has A Solution DONNA YOUNG [email protected]
GlaxoSmithKline PLC has offered up its new Maryland vaccine Ballou said the Rockville center already is equipped with laboratories research and development center, and its scientists, under the and manufacturing capabilities that meet the current good manufac- company’s proposal to establish a global collaboration for turing practice standards required by the FDA, although he acknowl- the pursuit of products that are commercially risky, but neces- edged some retrofitting may be in order. sary to address emerging infectious diseases, before a public The idea behind the proposal, he said, is to have a scientific advisory health crisis strikes. board agree on what platforms should be pursued – not necessarily GSK’s – and for what diseases, so the initial work could be done on a oo often in recent years, the world has found itself unpre- vaccine long before an infectious disease emergency erupts. pared for an emerging infectious disease, such as pandemic Ballou said the activities that are undertaken at the facility would be T influenza, Ebola and now Zika, and biopharmaceutical firms governed by an independent party, such as the World Health Organi- have been forced to shift into crisis mode, with their research and zation (WHO) or another body. development activities and other strategic plans upended in an at- “WHO would certainly be a major player in this in terms of setting tempt to come to the rescue to avert a catastrophe. the priorities,” he said. But, said Ripley Ballou, head of GlaxoSmithKline PLC’s Global Vac- Ballou said GSK has taken a “very open approach” in presenting its cines US R&D Center, his company’s leadership decided, “We cannot proposal to various entities and said the company is willing to partner continue to do business like this in the future.” with other firms on the strategy. “We will listen to any good idea that’s out there,” he insisted. But, Ballou said, “so far, we’re pretty much a voice in the wilderness on this” with no other biopharmaceutical companies stepping up to the plate to offer up their facilities or plans in a similar manner. “We are the only one that’s come with a plan that I know of,” he said.
MUST BE SUSTAINABLE But Ballou said GSK’s proposal “only makes sense if it is sustainable.” “We will put our technology on the table, we will put the facility on the table, but we need to know we can do this and not just for two years or three years on a grant,” he declared. “This needs something that has a long-term vision” – going well beyond an initial financial in- vestment. Ripley Ballou Anthony Fauci, director of the NIH’s National Institute of Allergy and Infectious Diseases, pointed out there’s been proposals put forward by the White House, some lawmakers on Capitol Hill, former Ebola “It’s too disruptive,” he declared. “czar” Ron Klain and computer mogul-turned-philanthropist Bill Gates But being a key player in the vaccines and medical countermeasures to establish a US contingency fund dedicated to supporting R&D for R&D arena, including its current work on vaccines against Ebola and vaccines and drugs against emerging infectious diseases that are con- the Zika virus with the National Institutes of Health (NIH), GSK couldn’t sidered public health threats. simply throw up its hands and walk away. Fauci suggested that pot of money, which would be separate from So the firm’s management, who were determined to find a better, the US government’s Project Bioshield’s Special Reserve Fund and less chaotic way, decided GSK would take a proactive approach and WHO’s Contingency Fund for Emergencies, could be replenished offer up a significant portion of the company’s new Rockville, Mary- through the normal “slow and deliberative” appropriations process. land-based vaccine center as a dedicated global facility – complete He argued that would be much more reliable than the current rush- with expert scientists and other staff – for working on products whose to-fund-the-crisis situation, where urgent dollars often end up in the commercial potential is risky, but whose public health need is likely to middle of a political fight, like what’s gone on with Zika, which has got- be great, Ballou explained. ten bogged down in a battle over restricting funds for birth control “This is a gap that hasn’t been filled yet and we think we have a services. solution,” he contended during a recent media briefing at the Rock- There were some efforts to get a dedicated public health emergen- ville center. cy fund put together last week, but it didn’t get very far before Con- Ballou said GSK has “talked to anyone who would listen to us” about gress recessed for its seven-week summer break. Lawmakers won’t its proposal, including the World Health Organization (WHO) and vari- return until after the US Labor Day holiday in early September. ous governments. Published online 07-18-2016
10 | Scrip intelligence | 29 July 2016 © Informa UK Ltd 2016 HEADLINE NEWS
J&J Thinks It Can Win Over Biosimilar Competition LISA LAMOTTA [email protected]
The big pharma reports strong 2Q earn- ings and executives talk about strategy for defending against biosimilar compe- tition in the US.
ohnson & Johnson doesn’t see much impact from biosimilar Remicade – at Jleast, not yet. The pharma bellwether reported solid second quarter earnings that could mean a swath of strong reports from its pharma brethren over coming weeks, but increased guidance doesn’t adjust for biosimilar Remicade entering the US market this year. “As we look at the landscape going for-
ward, we fully predict that generics and Images Creativa Shutterstock: biosimilars are going to be part of the competitive landscape. And we think that the next couple years. Biosimilars of AbbVie of such a launch after the expiration of the is essential for the healthcare system. We Inc.’s Humira (adalimumab) and Amgen 180-day waiting period enforced in the think in the long run, it’s actually a benefit Inc.’s Enbrel (etanercept) are under review Amgen v. Apotex case, which will be Octo- for very innovative-focused companies be- at FDA – so competition is coming. ber 6, 2016,” wrote Leerink Swann analyst cause that’s the only way you can relieve Merck & Co. Inc. handles Remicade mar- Geoffrey Porges in a July 19 note. “This will pressure over the long term,” J&J chair and keting in Europe. J&J reported minimal ef- obviously be an important event for the CEO Alex Gorsky told the company’s call fect so far, reporting only that Remicade Remicade franchise, for the TNF category, with analysts on July 19. exports have declined due to biosimilar and for the industry as a whole. That said, “And so we projected [biosimilars and entrants outside the US. JNJ still seems to be fighting their corner generics]. As we look at our strategic plan, J&J raised its guidance for the full year fiercely by defending other longer dura- we think they will be there. Also as we look of 2016, now expecting sales between tion patents, but 4Q this year does seem a at Remicade itself, we know that there’s $71.5bn to $72.2bn from a previous range possible date for first biosimilar launch.” about 2.4 million patients who’ve been of $71.2bn to $71.9bn. The increase came Porges points out that Remicade lost 1% treated with the compound. We know after the company announced a strong of its pricing power this year despite two that about 70% of them in fact are getting second quarter with sales of $18.48bn, up list price increases, likely due to J&J nego- good relief and good effects. We know 4% year-over-year. The pharmaceutical di- tiations with payers ahead of biosimilar that they’re unlikely to be switched when vision accounted for $8.65bn of total sales launches in the US. they’re getting a positive response from and was driven by strength from brands in J&J is typically the first pharma company the therapy.” immunology and oncology. to report earnings and often functions as J&J also sees strength in the breadth of “The company’s updated financial guid- a bellwether for the rest of the industry. its offerings and its standing as a health- ance does not include a Remicade launch Strong earnings from the multinational care giant. “We also know that when we in US this year, but the company appeared conglomerate could mean the next few contract across the Janssen and Johnson & to acknowledge on the call the possibility weeks of earnings report will be positive Johnson portfolio that it provides us a very for the industry. important position with larger healthcare As we look at the Porges agreed: “We previously noted systems and networks. So that’s the way that the second quarter historically coin- we think about it and that’s the way we landscape going forward, cides with the largest increases to guid- plan for it going forward,” the CEO added. we fully predict that ance in biotech, and believe the results for The firm’s guidance assumes no bio- JNJ’s pharma business support the trend. similar Remicade (infliximab) and Procrit generics and biosimilars Importantly, while investors give JNJ a pre- (epoetin alfa) will enter the US market in mium multiple compared to pharma and 2016. Samsung Bioepis Co. Ltd. has gotten are going to be part of the biotech peers, the main source of their biosimilars of infliximab and etanercept competitive landscape growth is their drug business, which looks through in Europe and the South Korean a lot like relatively mature drug businesses firm hopes to introduce biosimilars of oth- in other companies.” er tumor necrosis factor (TNF) inhibitors in Published online 07-19-2016 scripintelligence.com 29 July 2016 | Scrip intelligence | 11 POLICY & REGULATION BRIEFS
Update: Ziopharm Study Death Not Due To Drug Another Black Cloud Douses Four days after announcing that a third Valeant’s Sunlight patient had died during a Phase I clini- Downtrodden Valeant Pharmaceuticals International Inc. finally caught cal trial for its gene therapy, Ziopharm some sunlight this past week, with the Canadian company’s commercial Oncology Inc. confirms that the latest prospects getting somewhat of a boost after getting the go-ahead to mar- patient death (like the previous two) in ket an oral version of its opioid-induced constipation (OIC) drug Relistor its glioblastoma study is not related to (methylnaltrexone) and a recommendation from an FDA advisory panel the study drug. “Recurrent GBM is a dev- to permit the firm to sell its new plaque psoriasis drug brodalumab, albeit astating disease with an expected overall with a risk management plan. But then the FDA cast another big black cloud over Valeant – smacking it with a complete response letter (CRL) for its investigational eye treatment latanoprostene bunod over concerns about deficiencies at the firm’s Tampa, FL manufacturing facility. Valeant, which disclosed the CRL early on July 22, provided little insight into the problems identified by the FDA, which discovered the deficiencies during a current good manufacturing practice inspection at the plant, owned by the com- pany’s subsidiary Bausch & Lomb Inc. Valeant emphasized the FDA didn’t
Shutterstock: Shutterstock: Valeriy Evlakhov identify any efficacy or safety problems with the new drug application (NDA) for latanoprostene bunod, which the company is seeking to market survival that remains far too short as this as an intraocular pressure lowering single-agent eye drop for patients with case illustrates,” Francois Lebel, exec VP open angle glaucoma or ocular hypertension. Nor did the agency request of R&D and chief medical officer at Ziop- any additional clinical trials to approve the NDA, the firm toldScrip . Valeant harm, said in a statement. “Preliminary has asked the FDA for a meeting to work on a resolution and address the overall survival in this study, including a agency’s concerns. Wells Fargo analyst David Maris, who called the rejec- median follow-up of over eight months tion “unexpected,” emphasized that if the CRL is a sign of broader issues in the first dose cohort, remain encour- at the facility, “this could be serious for Valeant,” since it appears that the aging, and we will continue to work Tampa plant is where a broad range of the company’s products are made diligently toward understanding the full and it’s also a contract manufacturing facility. With the significant chal- potential of Ad-RTS-hIL-12 + veledimex lenges Valeant already is facing with the various federal and congressional in this disease, with the goal of provid- ongoing investigations into the company, any disruption to its manufactur- ing safe and effective treatment options ing could “negatively impact a business that is already distracted,” he said. to these patients.” The Boston-based bio- “We believe it is natural for investors to question whether this is an isolated tech disclosed in a workshop slide pres- incident or a reflection of the severe cost-cutting model that Valeant has entation on July 14 that a third patient employed,” Maris said. The sales expectations for latanoprostene bunod, has died during the ongoing Phase I trial which has had two different trade names tied to it – Vesneo and Vyzolta of Ad-RTS-hIL-12 with orally adminis- – neither of which the FDA has signed off on, are essentially “unimpor- tered veledimex in recurrent or progres- tant,” he said. But if the FDA’s concerns are an indication of broader manu- sive glioblastoma. The slides were in- facturing issues, “this is very important,” Maris warned investors. Valeant, cluded in a filing with the US Securities however, said the deficiencies the FDA found were unrelated to any other and Exchange Commission. The patient product being manufactured at the facility. TD Securities analyst Lennox was part of the third cohort in the study, Gibbs took a brighter point of view of the CRL – emphasizing the FDA’s which received Ziopharm’s gene therapy efficacy and safety evaluation is the most difficult obstacle for an NDA to Ad-RTS-hIL-12 via a shot straight into get past, and Valeant’s latanoprostene bunod “appears to have cleared that the brain tumor and then was given 30mg hurdle.” Nonetheless, the drug’s path to market likely will be delayed due of oral veledimex, a compound meant to to the chemistry, manufacturing and controls portion of the process, Gibbs dial-up or dial-down the amount of the said. And, he said, that delay is likely to be costly. protein interleukin-12 to stimulate the Published online: 07-22-2016 immune system. The patient died of an intracranial hemorrhage 15 days after starting the drug. There were deaths in Ad-RTS-hIL-12 plus 40mg of veledimex. company said. Enrollment in the study is each of the two earlier cohorts – one pa- tient died 6.4 months after receiving Ad- The first death was due to disease pro- still ongoing and the company expects to RTS-hIL-12 plus 20mg of veledimex and gression and the second was also deter- provide updates in the future. the other died 3.9 months after receiving mined not to be related to study drug, the Published online: 07-19-2016
12 | Scrip intelligence | 29 July 2016 © Informa UK Ltd 2016 HEADLINE NEWS
Suicide Warnings For Valeant’s Siliq Could Hinder Access To Psoriasis Treatment While an FDA advisory committee unanimously supported approval of the plaque psoriasis drug brodalumab, several recommended a black box warning on suicide risk that could limit sales of the drug. MICHAEL [email protected] [email protected]
he variety of strict safety recom- EXACERBATED BY REMS? depression. That phrasing could discour- mendations from the FDA’s Derma- Gibbs also cited a mandatory registry as a age physicians from using the drug even T tologic and Ophthalmic Drugs Advi- crippling aspect of sales and patient access. in patients without a history of depression. sory Committee could have the unintended Fourteen of the panelists supported “Clinicians need to be aware that this consequence of limiting access to Valeant approval for Siliq only if risk management is not a suicide that is just going to occur Pharmaceuticals International Inc.’s plaque options beyond labeling, such as a Risk within the subject of depression,” Irwin psoriasis candidate Siliq (brodalumab), Evaluation and Mitigation Strategy, were said. “It might come out of the blue, so to should it reach the market. implemented to address suicidal ideation speak, and be impulsive.” Although all 18 panelists recommended and behavior. Many of these members Irwin was among the 14 panelists who the treatment for approval, several said called for a mandatory registry as part of backed approval for Siliq only if FDA insti- they would only support the FDA’s backing a REMS. tuted risk management beyond labeling, if the labeling for the drug includes a black box warning for the potential drug-related risk of suicide ideation and behavior. Suicidal ideation and behavior was the primary focus of discussion during the meeting. There were six completed sui- cides in brodalumab’s clinical development program, raising questions about whether there was a drug-related risk. Committee chair Michael Bigby and patient represen- tative Elizabeth Smith were among the panelists calling for a black box warning. But other members cautioned of such strict measures with concerns that they may prevent the drug from getting to patients who need it. Panelist Matthew Levai Aleksandar Shutterstock: Rudorfer, chief of the somatic treatments and psychopharmacology program at the Valeant consultant Mark Lebwohl ap- including a mandatory registry. He did not, National Institute of Mental Health, warned peared to have confirmed fears that sui- however, specify that his warning should that strict post-marketing measures could cide warnings would hinder patient access be a black box. scare people away from using and pre- to the drug. Lebwohl, who is a professor of Valeant officials tried to downplay the risk scribing what he called an effective drug. dermatology at the Icahn School of Medi- of suicide posed by the drug. They noted that Analysts had mixed reviews about Siliq’s cine at Mount Sinai, said during a conver- most of the suicides occurred due to circum- commercial potential if approved with a sation about a registry that he would not stances outside of depression. For example, black box warning. Raghuram Selvaraju prescribe the drug to patients who he feels one of the subjects was about to go to jail, of investment bank Rodman & Renshaw are at risk of suicide, such as patients with while another had lost his disability payments. Capital Group said in a research note that depression. The Canadian drug maker added that the treatment could generate between “If a patient came to me and I was wor- depressive symptoms had worsened in the $400m and $500m in sales despite a black ried about suicide in that patient, there is placebo group more than in patients tak- box warning if approved, pointing to its no way they would be getting this drug,” ing Siliq. “solid efficacy.” Lebwohl said. FDA has until Nov. 16 to make a deci- Conversely, TD Securities Inc. analyst Michael Irwin, a professor of psychiatry sion on the drug. Originator Amgen Inc. Lennox Gibbs gave a more grim assess- and biobehavioral sciences at the David dropped the drug after the suicide issue ment of a black box warning. He said in a Geffen School of Medicine at UCLA, sug- came to light, and former partner Astra- note that such a warning would be one of gested the drug include in a warning that Zeneca PLC subsequently licensed broda- the most damaging components to pa- suicides can occur without a patient nec- lumab to Valeant. tient access and sales. essarily showing symptoms of anxiety and Published online 07-22-2016 scripintelligence.com 29 July 2016 | Scrip intelligence | 13 BUSINESS BULLETIN
Biocon Stays The Course For Neulasta, Herceptin Chronos’ Deal With Shire Is ‘Just The Biosimilars Start’ Of Its Acquisitive New Strategy India’s largest biopharmaceutical firm Chronos Therapeutics’ acquisition of three preclinical central nervous Biocon Ltd. reported a 17% increase in system (CNS) disease-targeting assets from Shire PLC is the first of a pos- net profits to INR1.47bn ($21.9m), with sible series of deals the emerging biotech is seeking under its new busi- revenues up 11% to INR9.52bn in the ness strategy. In 2015 Chronos made the decision to pursue an acquisition first quarter ended June 2016. The strong strategy for new assets to develop alongside its own preclinical CNS and showing was backed by all round growth obesity programs. Now, with Shire as a new equity investor and pharma across business verticals; the biologics partner, Chronos has big plans to secure more financing to enable it to business was up 53% powered by sales of move its three new compounds into the clinic simultaneously. The three biosimilars in emerging markets. Shares programs UK-based Chronos has picked up from Shire are preclinical of Biocon shot up by over 15% to end compounds targeting indications of fatigue in multiple sclerosis (MS), ad- at INR808.70 on the Bombay Stock Ex- dictive behaviors and potentially post-traumatic stress disorder. Financial details of the deal were not disclosed but Shire has become an equity in- change on July 22. The Bengaluru-based vestor in privately held Chronos as part of the agreement. Shire will also firm underscored that it stays on course have first negotiation rights to these assets in the future should Chronos to taking its biosimilars portfolio, part- look to partner or divest them. Chronos has acquired all intellectual prop- nered with Mylan NV, to Europe and the erty, know-how, development and marketing rights for each program on a US. Biocon said that the European Medi- worldwide basis. CEO of Chronos, Huw Jones, told Scrip the company was cines Agency (EMA) had accepted for re- interested in Shire’s preclinical programs because the assets “have been view Mylan’s Marketing Authorization well-managed previously, they represent targets within the CNS space we Application (MAA) for pegfilgrastim, are interested in and they are targeting diseases with high unmet medical their proposed version of Amgen Inc.’s needs.” All of this provides Chronos with a strong commercial opportu- Neulasta. “The application will undergo nity when developing these drug candidates, Jones said. The company has the review process and this kicks off the evaluated hundreds of partnership opportunities, according to Jones, to process of filing of multiple biosimilar move forward with its 2015 board decision to buy-in more assets for its applications over the course of this fis- minimal pipeline. Chronos has a broad definition of CNS disease which cal,” Biocon’s chair and managing direc- includes degenerative and behavioral brain disorders and Jones believes tor, Kiran Mazumdar-Shaw, said at a post this sets the company apart in the CNS-orientated biotech space. “Over results investor call on July 22. While Eu- the last few years we have focused a lot of expertise in degenerative and be- ropean approval timelines can vary from havioral brain disease,” he said. “We have a unique concentration of both case to case, one to one-and-a-half years is these areas in a small company. We are nimble, we can move quickly when the general estimate, the Indian firm in- it is needed.” In the short-term, Chronos will focus on integrating its new dicated on the call. In addition to analyti- products from Shire and developing robust clinical development plans for cal, functional and pre-clinical data, the the compounds. However, looking further ahead, Jones said the company application includes clinical data from would seek further deals or acquisitions. “Further deals are on the hori- pivotal pharmacokinetic/pharmacody- zon and this deal with Shire is just the beginning,” Jones told Scrip. “If the namic (PK/PD) and confirmatory effi- structure and technology are a good fit and the target is complementary to cacy, safety and immunogenicity studies what we already have in the pipeline then we will be interested.” completed earlier in 2016, a statement Published online: 07-20-2016 from the partners said. Published online: 07-22-2016
agreement to acquire worldwide devel- taining rights in the two Asian markets, Galderma Steps Into Biologics opment and marketing rights, except in Roche-owned Chugai will manufacture Japan and Taiwan, to the Japanese com- and supply the product as part of the al- With Chugai Eczema Antibody pany’s nemolizumab (CIM331), an anti- liance. The antibody will be positioned Dermatology specialist Galderma SA is interleukin-31 receptor A antibody that for moderate to severe atopic dermatitis making its first foray into the world of has recently completed an international (eczema) and will add to a stable of mar- biologic therapies through a major deal Phase II trial. Financial terms were un- keted conventional Galderma products with Chugai Pharmaceutical Co. Ltd. for disclosed but the deal includes upfront, for this indication, including the corti- a novel antibody against atopic dermati- milestone and royalty payments from costeroid Clobex (clobetasol). tis. The Swiss firm has entered into an privately held Galderma. As well as re- Published online: 07-20-2016
14 | Scrip intelligence | 29 July 2016 © Informa UK Ltd 2016 HEADLINE NEWS
Changes Brewing At Bayer, But Pharma Strategy Remains On Point JESSICA MERRILL [email protected]
If Bayer executes on the acquisition of seed maker Monsanto, the wide range of business development opportunities. Business devel- company’s agriculture business will more than double, surpass- opment will be focused on three therapeutic areas, however: car- ing pharmaceuticals as the top revenue generator, but manage- diovascular disease, oncology and women’s health. Bayer, like other ment said its commitment to pharma remains unchanged. innovative pharmaceutical manufacturers, is focusing increasingly on therapeutic areas where it can achieve a leadership position. ayer AG is pursuing an acquisition of seed manufacturer Mon- “I think it is all about franchise leadership,” Malik said. “It starts santo Co. that would establish agriculture as the largest busi- right from the earliest point that you build up core competencies.” Bness unit within the diversified life sciences company, usurping For Bayer that means building on its long heritage in cardiovascular pharmaceuticals as the top revenue generator. Bayer Head of Inno- disease and women’s health and expanding in oncology. vation Kemal Malik said the company’s commitment to pharmaceu- In cardiovascular disease, the company is hoping to build on the ticals remains unwavering despite the M&A play. success it has had with Xarelto even though new blockbusters in Pharmaceuticals has been Bayer’s largest business segment under the therapeutic area are rare in today’s market. The recent launches a new structure put in place at the beginning of the year, generating of two new PCSK9 blockers for cholesterol, Amgen Inc.’s Repatha €13.75bn ($15.13bn) in 2015, while CropScience generated €10.37bn (evolocumab) and Sanofi/Regeneron Pharmaceuticals Inc.’sPralu - ($11.41bn). But the acquisition of Monsanto would dramatically ent (alirocumab), as well as Novartis AG’s new heart failure drug change the business balance, more than doubling the size of the ag- Entresto have highlighted the challenges. riculture business and moving pharma to the number two position. Bayer recently announced it would stop the Phase III develop- Monsanto, based in St. Louis, Mo., generated sales of $15bn in 2015. ment of the mineralocorticoid receptor antagonist finerenone for “We have full and total commitment to our pharma business,” Ma- congestive heart failure for commercial reasons, though it is con- lik said in an interview July 18. He pointed to the company’s increas- tinuing to develop the drug in diabetic kidney disease. ing investment in pharmaceutical R&D as evidence of Bayer’s pledge But Malik said the decision was related to the drug, not the thera- to the space. “We are spending over €1bn more in R&D in pharma peutic area. “The challenge we had with finerenone is while it was in 2016 than we spent in 2012,” he said. “It’s a visible demonstration, a relatively unique agent, it did work in a similar way to two agents not just words, that we are fully committed to our pharma business.” on the market, spironolactone and eplerenone, and they are both Bayer spent €2.83bn on healthcare R&D in 2015, up from generic. Whatever we achieved in our Phase III program, ultimately €2.26bn in 2014, of which the vast majority – €2.33bn –was dedi- there was always the risk of it being seen as a class effect, and so the cated to pharma. value proposition just wasn’t there for us.” A few days before the interview, on July 14, Bayer confirmed it en- The company is continuing to develop other drugs for heart fail- gaged in private discussions with Monsanto and raised its all-cash ure, including the guanylate cyclase (sGC) stimulator vericiguat in offer for the company to $125 per share from $122 per share, a value collaboration with Merck & Co. Inc. and other earlier pipeline assets. of about $64bn. The company first announced an offer to buy Mon- Nonetheless, Malik acknowledged that the industry’s Lipitor days santo May 19 to strengthen its agriculture business, one of three pil- are probably over. “It’s just much more of a hard process,” he said. lars at the company. “From the time you launch, there are multiple steps and hurdles that On July 19 Monsanto issued a statement saying the offer is inad- you have to get through. Those are reimbursement related, but also equate, but that it remains open to buyout discussions related to being on treatment guidelines, and that takes time.” Bayer’s other two primary business units are pharmaceuticals In oncology, Bayer has had success with Nexavar (sorafenib) in liver and consumer health, after Bayer spun out its material science busi- and kidney cancer and the next-generation kinase inhibitor Stivarga ness into a separate new company called Covestro last October. (regorafenib), approved for metastatic colorectal cancer and gastro- ([A#SC030185]) The unit was previously second behind pharma- intestinal stromal tumors. The company released positive Phase III ceuticals, generating €11.98bn in 2015. Meanwhile, the company data testing Stivarga in liver cancer in May. already expanded its consumer healthcare business with the ac- The company hasn’t been keeping up in immuno-oncology, howev- quisition of Merck & Co. Inc.’s consumer health segment in 2014. er, an area the world’s leading oncology players are heavily invested in. With a new structure and a new CEO, Werner Baumann, who Malik acknowledged the company missed the first wave of in- took over the leadership role in April, Bayer is in the midst of a novation in immuno-oncology, the PD-1/L1 inhibitors. “It would be transition. The leadership change appears to have been a smooth insane for us to now either insource or develop on our own one,” succession, however, and the strategy under Baumann, a 28-year he said. “For us, it is going to be the next wave of innovation. There veteran of the company, remains largely focused on executing the will be further innovation in the immuno-oncology space. We are one CEO Marijn Dekkers had been working toward. looking at different types of targets and that’s where our efforts are The company’s mega-deal is focused on agriculture, but on the concentrated in R&D.” pharma side of the business, Malik said Bayer remains interested in a Published online 07-20-2016
scripintelligence.com 29 July 2016 | Scrip intelligence | 15 HEADLINE NEWS
Merck Singapore R&D Collab Looks To Get Peptides Into Cells Merck & Co is tapping government scientific researchers in Singapore to help overcome some of the limitations of macrocyclic peptide therapeutics. IAN HAYDOCK [email protected]
he potential of macrocyclic peptides to reach traditionally the action on intracellular targets of some already well-established “undruggable” therapeutic targets has one major current lim- natural source-derived macrocyclics such as the oral immunosup- T itation - their limited ability to penetrate into cells to reach pressant ciclosporine. those targets. Merck Sharp & Dohme Ltd. is now looking for new Dr. Brown said the MSD collaboration - which will involve up to ways to overcome this hurdle through an R&D collaboration with around 10 researchers from the A*STAR side and Merck’s global Singapore scientists. R&D network - will focus on elucidating rational approaches to MSD - Merck & Co. Inc.‘s operating entity outside North America peptides transport, building on basic research already underway - is working with Singapore’s Agency for Science, Technology and within the lab and agency. Research (A*STAR) in a two-year program that aims to elucidate “This will include looking at naturally occurring carrier toxins and bring down some of the technical and biological barriers to such as Pseudomonas endotoxin A, scaffold approaches, different improved intracellular delivery, which is seen as unlocking more of formulations, the use of endosomes, and also research related to the inherent potential of macrocyclic peptides. p53 endian 2,” he told Scrip. Endosomes, membrane-bound cyto- plasmic vesicles, transport molecules taken into cells, while p53 endien 2 is a negative regulator of the p53 tumor suppressor gene. A*STAR was unable to divulge further details of the specific thera- peutic or cellular targets that would be the focus of the MSD collabo- ration, but did confirm to Scrip that the company would hold rights to any technology emerging specifically from the collaboration. MSD added in a statement that the hope is to advance the ability “to apply peptide therapeutics to highly validated intracellular tar- gets that have historically been out of reach,” and Dr. Brown noted that approaches coming out of the tie-up might potentially find Shutterstock: alice-photo Shutterstock: non-peptide biologic applications as well.
Researchers from MSD will work with several of A*STAR’s 18 enti- NOT ALONE ties including the Bioinformatics Institute, Institute of Chemical and Given that intracellular protein-protein interactions are involved in Engineering Sciences, Institute of Molecular and Cellular Biology, many disease processes including cancer metastasis and inflamma- and the p53 Laboratory under director Professor Sir David Lane, the tion, macrocyclic peptides are being broadly investigated in various cancer researcher who is also A*STAR’s chief scientist. settings. Globally, various research projects are also underway look- The main aims of the tie-up, financial terms of which were undis- ing at the potential use of nanocarriers such as liposomes, micelles, closed, is to elucidate processes influencing peptide cell penetra- polymer nanoparticles to help get them into cells. tion and to look at “smart” delivery systems based on natural cell A*STAR pointed to projections that the global peptide therapeu- entry mechanisms. tics sector as a whole could reach $23.7bn by 2020. Work will be geared very much towards “establishing a proof of Specialist companies already working on macrocyclic peptide concept approach,” Dr. Chris Brown, a research scientist at A*STAR’s therapeutics include the listed Japanese bioventure PeptiDream p53 Lab, told Scrip. Inc., which has developed a proprietary platform for the genera- tion and rapid screening of large and structurally diverse libraries MACROCYLIC ATTRACTIONS against specific targets. Macrocyclics possess a unique ring structure that enables them to The Tokyo University spin out already has numerous big pharma block disease-related intracellular protein-protein interactions that collaborations including with GlaxoSmithKline PLC, Novartis AG have so far been largely out of bounds to conventional therapeutic and Bristol-Myers Squibb Co., the last company having progressed approaches. a joint immuno-oncology program into Phase I trials. The lack of clear binding sites or receptors on many proteins pre- Others working on cell-permeable macrocyclic peptide thera- vents small molecules from targeting specific protein interactions, peutics include the private US venture Circle Pharma Inc., which which also cannot be targeted by antibodies as these are too large has a partnership with Pfizer Inc. and is pursuing potential oncol- to enter cells and therefore usually act at the cell surface. ogy applications through the Wnt/beta-catenin pathway and epi- The molecular structure of macrocyclics potentially allows high genetic regulation. affinity and potent binding to specific protein surfaces, mimicking Published online 07-20-2016 From the editors of PharmAsia News.
16 | Scrip intelligence | 29 July 2016 © Informa UK Ltd 2016 R&D BITES
Approval Might Be The Least Of Aralez’s Challenges With Amgen Files Osteoporosis Drug Yosprala In US Ahead Of Rival Merck Canadian specialty firm Aralez Pharma- Amgen Inc. and UCB Group have appeared to lock in their head start in ceuticals Inc. is confident that its heart the race to get new osteoporosis biologics market, with the July 21 an- attack and stroke-prevention combina- nouncement that they had submitted the biologics license application tion product Yosprala will gain FDA (BLA) submission to the US FDA for their investigational monoclonal approval on a third review, but that will antibody romosozumab. The drug works by binding and inhibiting scle- only be the beginning of the company’s rostin (a protein naturally occurring in the bone) thereby increasing bone challenge as it attempts to position the formation and decreasing bone resorption. Biomedtracker has granted ro- controlled-release formulation of as- mosozumab a likelihood of approval rating of 64%, four percentage points pirin and omeprazole against generic above the average rating for a product at a similar stage of development. and over-the-counter products. Yospra- Amgen and UCB’s offering is the most advanced osteoporosis product in la combines aspirin with the proton development targeting sclerostin – its closest rivals are Mereo BioPharma pump inhibitor omeprazole (AstraZen- Group Ltd., which has BPS804 in Phase II trials for osteogenesis imperfect, eca PLC’s Prilosec and generics) to im- and Eli Lilly & Co., which is developing a Phase I osteoporosis biologic prove tolerability. Aralez’s predecessor known as blosozumab. But Amgen might need its current head start with Pozen Inc. received two FDA complete the US regulators if it wants to beat its most relevant opponent Merck response letters due to inspection defi- & Co. Inc. to market, as the US pharma giant also has a Phase III drug ciencies at a supplier: it brought in a new targeting osteoporosis in the postmenopausal population waiting in the supplier for the aspirin component of wings. Merck’s odanacatib is an inhibitor of cathepsin K, which also treats the combination product and re-filed its osteoporosis through decreased bone resorption. Submission to the FDA NDA, which has an action date of Sept. had been delayed by the need for additional cardiovascular safety analyses, 14. The company is working on prepar- but it is slated for US approval in 2017 and has a likelihood of approval ing both its prescriber and patient bas- rating from Biomedtracker of 63%. Furthermore, the product is expected es. Speaking to the Cantor Fitzgerald to achieve much stronger worldwide sales, approximately $1.8bn by 2023. Healthcare Conference July 13, Aralez Click here to view approved osteoporosis therapies in US: http://bit.ly/29ZgKkw CEO Adrian Adams said his company is Published online 07-22-2016 leveraging a smaller product, the choles- terol drug Fibricor (fenofibrate), to pre- pare its target market of cardiologists and primary care physicians for an ex- results were presented, and was dismayed profile,” Xie Dong, chief scientific -of pected launch of Yosprala in the fourth by adverse comments about the study. ficer of developer Nanjing Frontier Bi- quarter of 2016. It has also started a pa- Published online: 07-20-2016 otech Co. Ltd., said in a statement. The tient education to tout aspirin’s cardio- open-label study compared albuvirtide protective advantages. with lopinavir plus ritonavir in HIV-1 Published online: 07-20-2016 China’s First Home Grown infected adults failing their first-line treatment. The drug was given once Novel HIV Drug Shoots For weekly via intravenous infusion against XBiotech Stands By Prime Time the primary endpoint of percentage of participants with plasma HIV-1 RNA Advanced Colorectal Cancer A new fusion inhibitor that prevents HIV entry into cells, albuvirtide, has levels suppressed to fewer than 50 Phase III Study reached its primary endpoint in a Phase copies/mL at week 48. Albuvirtide is a XBiotech Inc. thought there would be a III trial conducted in China, opening synthetic peptide chemically related to positive response to the presentation of the way to the possible approval in this Roche’s Fuzeon (enfuvirtide), the only pivotal Phase III data on its lead prod- market of what would be the country’s approved fusion inhibitor. However, uct candidate, Xilonix (MABp1), at the first domestically developed origi- Fuzeon must be administered by sub- European Society of Medical Oncology nal drug for the disease. “The results cutaneous injection twice daily, poten- (ESMO) World Congress on Gastroin- show that albuvirtide is equivalent tially giving Frontier’s drug the edge in testinal Cancer at the start of July, but in efficacy to the current second-line convenience and ease of use. In China, it was sadly disappointed. The company treatment recommended by the World providing additional treatments for found itself under what appeared to be a Health Organization [lopinavir plus ri- HIV carriers is particularly significant. short-selling attack on its shares after the tonavir], and with a better renal safety Published online: 07-21-2016 scripintelligence.com 29 July 2016 | Scrip intelligence | 17 HEADLINE NEWS
Key Clinical Data And Drug Approvals Expected In 2H 2016 ALEX SHIMMINGS [email protected]
As July is already upon us, Scrip takes a Guselkumab is being tested at the 100 ONCOLOGY look at some of the more interesting clini- mg dose which has shown promising re- In cancer, major Phase III readouts expect- cal trial read-outs and drug approvals ex- sults in Phase II compared with placebo ed by the year end include the COLUM- pected clinical trials due to report in the as well as head-to-head against Humira BUS study of a combination of Array Bio- second half of the year. (adalimumab). The primary endpoint of Pharma Inc.’s binimetinib and encorafenib PGA score of either 0 or 1 at week 16 was in melanoma. he constant churn of activity in the achieved in 86% of patients versus 58% Array is also developing binimetinib, a anti-inflammatory sector will con- with Humira (p<0.05). Additionally, at week MEK inhibitor, and encorafenib, a BRAF in- T tinue, with novel products set to 16, 79% and 62% of patients on guselkum- hibitor, independently for melanoma but produce key data as approval is awaited ab achieved PASI 75 and PASI 90, respec- top-line results from COLUMBUS, which for the first biosimilar version of AbbVie tively. is comparing the combination against Inc.’s top-selling anti-TNF agent Humira The VOYAGE studies will look to replicate Roche’s Zelboraf (vemurafenib) in 900 pa- (adalimumab). these results, while the NAVIGATE trial will tients with locally advanced unresectable Amgen Inc. is leading the race to be evaluate a direct comparison of gusel- or metastatic melanoma with the BRAF first with a highly anticipated biosimilar kumab to Stelara. “In an indication with an V600 mutation, are expected in the third Humira, with an FDA Biosimilar User Fee already wide-range of treatment options, quarter. Act (BsUFA) target action date set for Sep- guselkumab will need to be able to show In June, Array submitted an NDA for tember 25, but delays appear likely con- superiority to Humira or Stelara in some binimetinib monotherapy in patients with sidering previous 351(k) applications, say patient population in order to claim a share advanced NRAS-mutant melanoma ( a rel- analysts at Biomedtracker. Indeed while of the market,” say analysts at Informa Phar- atively small indication) based on the posi- the FDA’s Arthritis Advisory Committee ma’s Biomedtracker. tive results of the pivotal Phase III NEMO unanimously voted to approve the prod- Its competitor, Valeant’s Siliq (broda- study. Array expects to submit regulatory uct, there was some concern among the lumab), has just been past its Adcom test filings for the combination therapy in the panelists over how well they understood in plaque psoriasis. The product was previ- second half of 2016, for which the COLUM- issues around biosimilars. SC096878 Am- ously offloaded by both Amgen and Astra- BUS read-out is crucial. gen’s biosimilar Humira also awaits ap- Zeneca on concerns over suicidality that The Array combination will approach ter- proval in Europe, and a decision from the formed a major part of the panel’s discus- ritory held by Novartis AG’s combo of Me- CHMP is expected between September sion, but these issues have not totally de- kinist (trametinib) and Tafinlar (dabrafenib), 2016 and March 2017. railed the product as yet. which are approved alone and in combina- Amgen faces upwards of 17 competitors Meanwhile, J&J should hear from the US tion with each other to treat unresectable in the market for biosimilar adalimumab. FDA on its supplemental BLA for Stelara in or metastatic melanoma in patients with Amgen’s closest contender is Novartis’ another indication, Crohn’s disease, by the a BRAF V600E or V600K mutation. The two biosimilar version; the Swiss company ex- end of September. Stelara is already ap- therapy duos may struggle to gain ground pects to submit its application by the end proved in the US for the treatment of pso- in the melanoma market, however, given of 2016. riasis and psoriatic arthritis. The agency is the strong efficacy and quick uptake of But novelty is still a major theme in reviewing data from the Phase III UNITI clin- immunotherapies – the programmed cell anti-inflammatories, with plenty of news ical program, which includes three studies death-1 (PD-1) inhibitors. ahead. Top-line data from all three Phase III (UNITI-1, UNITI-2 and IM-UNITI) evaluating Further top-line data for Infinity Pharma- studies for MorphoSys AG and Johnson & induction and maintenance treatment in ceuticals’ PI3K inhibitor duvelisib are due by Johnson’s guselkumab (VOYAGE 1, VOYAGE patients with moderately to severely active the end of September, this time from the 2 and NAVIGATE) in psoriasis are due by Crohn’s disease. DUO study. This will mark the first Phase the end of the third quarter. Success here The company is hoping that Crohn’s will III pivotal data release for chronic lympho- could lead to a BLA submission by the end find its niche as an alternative to the anti- cytic leukemia (CLL)/small cell lympho- of the year. TNFs to reduce the risk of side-effects. cytic lymphoma (SLL) and for the drug as The fully human monoclonal antibody “Due to the success of Stelara in pivotal a whole. Just last month, the company re- leased disappointing data from the Phase that targets the p19 subunit of IL-23 may studies for the treatment of Crohn’s disease, II DYNAMO study in indolent non-Hodgkin have a higher specificity for IL-23 than in addition to widespread success in other lymphoma (iNHL): the trial’s primary end- J&J’s already-approved blockbuster, Stelara indications, we anticipate that the FDA will point was met but the data were not as (ustekinumab), which binds to both IL-12 grant supplemental approval to Stelara on good as hoped. and IL-23. the first review,” says Biomedtracker. CONTINUED ON PAGE 19
18 | Scrip intelligence | 29 July 2016 © Informa UK Ltd 2016 HEADLINE NEWS
PD-1 EXPANSION Other major news expected in the car- tients receiving intravenously applied an- Two regulatory developments are due diovascular area includes further Phase III tibiotic (ceftriaxone). “These results will be for the PD-1 inhibitor immune-oncology data for Pfizer’s PCSK9 inhibitor bococizum- sure to set the pace for all future develop- powerhouses, Keytruda (Merck & Co. Inc.’s ab due to be presented at the American ment of SYN-004 including the anticipated pembrolizumab) and Opdivo (Bristol-Myers Heart Association meeting in November. Phase III trial that is expected to initiate Squibb Co.’s nivolumab), in the additional This product is lagging behind the first two later this year,” says Biomedtracker. indication of head and neck cancer. Both PCSK9 inhibitors, which were launched last companies will also report data for their re- year and have, so far, failed to set the world NASHVILLE spective products at ESMO in another key alight with their sales, but Pfizer maintains Another active area of drug R&D, for non- indication, PD-L1 positive non-small cell its product can become the market leader, alcoholic steatohepatitis (NASH), is set to lung cancer. based on the broad patient population in- see mid-stage data for two novel therapies The FDA granted a priority review to volved in its pivotal trial program. by the end of the year. Merck’s sBLA for Keytruda for the treat- Pfizer has already announced positive Cenicriviroc is Tobira Therapeutics Inc.’s ment of patients with recurrent or meta- top-line data from three of its five LDL stud- lead product candidate, a first-in-class im- static head and neck squamous cell carci- ies in its SPIRE program (SPIRE-HR, SPIRE-FH munomodulator and dual inhibitor of two noma with disease progression on or after and SPIRE-SI) trials, and data from the other chemokine receptors, CCR2 and CCR5. platinum-containing chemotherapy with a two (SPIRE LDL, SPIRE-LL) are expected by These pathways play a key role in the cycle PDUFA action date of Aug. 9, 2016. year end. Two further outcomes studies are of inflammation and fibrosis. The company Bristol-Myers Squibb should hear from ongoing SPIRE-1 and SPIRE-2, and another is testing the drug in a range of indications the FDA on November 11 on squamous cell study looking at a pre-filled pen formula- also including primary sclerosing cholangitis. carcinoma of the head and neck. The sub- tion (SPIRE-AI). Top-line data from an ongoing 289-pa- mission was based on Phase 3 CHECKMATE Analysts at Deutsche Bank Research note tient, placebo-controlled Phase IIb CEN- 141, in which Opdivo met its primary end- that Pfizer is the only company with a car- TAUR trial in patients with NASH and early point of overall survival compared with in- diovascular outcomes trial in high-risk pa- liver fibrosis will be available in the third vestigator’s choice of therapy. Further data tients who are unable to get their LDL lev- quarter. Given that this patient population are also due in PD-L1-positive, bladder can- els below 100mg/dL on maximum dose of is at the highest risk of developing cirrhosis cer and follicular lymphoma later this year. statins. “This is a patient population where and liver cancer, the FDA granted the drug Pfizer believes it is likely to show benefit. The a Fast Track designation shortly after the CARDIOVASCULAR second cardiovascular outcomes trial is in a trial began. BMS also has a stake in the fate of Portola broader patient population, testing whether Cenicriviroc has already demonstrated Pharmaceuticals Inc.’s universal Factor Xa reducing LDL levels below the current rec- that it is well tolerated and associated reversal inhibitor Ardexxa (andexanet alfa), ommended level will confer an additional with improvement in insulin sensitivity in which has a PDUFA action date of Aug. 17, morbidity and mortality benefit,” they say. a previous Phase IIa study in obese and having been granted a priority review by prediabetic or diabetic patients with sus- the FDA. C DIFFICULTIES pected NAFLD (non-alcoholic fatty liver Portola Pharmaceuticals is developing Moving to infectious diseases, Merck & Co disease), the precursor to NASH. While Andexxa as a universal anticoagulant re- is expecting news imminently of its novel insulin resistance is implicated in NAFLD versal agent for patients who experience treatment for Clostridium difficileZinplava pathogenesis, there is still continued de- a serious uncontrolled bleeding event or (bezlotoxumab), a fully human antibody bate as to whether it represents a cause who require urgent or emergency surgery. developed to target and neutralize the ef- or consequence. Nevertheless, the results The BLA is supported by the Phase III AN- fects of Toxin B produced by the bacterium, were encouraging for cenicriviroc’s thera- NEXA studies which evaluated the safety which has a PDUFA action date of July 23. peutic potential in NASH. “The upcoming and efficacy of Andexxa in reversing the -an This is a field of great unmet need and in- data readout from CENTAUR will feature ticoagulant activity of the Factor Xa inhibi- creasing development activity. Synthetic one-year treatment data on the primary tors rivaroxaban (Bayer AG/Johnson & John- Biologics is awaiting the read out of top-line endpoint and provide valuable insight son’s Xarelto) and apixaban (Pfizer Inc./BMS’s Phase IIb results for its offering SYN-004, a into this novel approach of treating NASH,” Eliquis) in older healthy volunteers. The second-generation beta-lactamase enzyme says Biomedtracker. expectation is that the arrival of the anti- under development, which degrades beta- Meanwhile, Galectin Therapeutics Inc. is dote will embolden physicians to use these lactam antibiotics excreted in the intestines. awaiting Phase II results for GR-MD-02, a newer oral anticoagulants (NOACs), which This degradation is expected to protect the carbohydrate-based galectin-3 protein in- have struggled to gain as much traction as gut microbiome from disruption by residual hibitor, from the NASH-FX study of NASH hoped. The development would help these antibiotic, and thus prevent opportunistic patients with advanced fibrosis, due at the companies catch up with Boehringer In- infections like C difficile. end of September. The product has a US gelheim, which has already gained EU and One of the key outcomes from this Phase fast-track designation for this indication US approval for Praxbind (idarucizumab), a IIb result is whether SYN-004 can prevent and is also in the Phase II NASH-CX study in reversal agent for its rival NOAC, the direct antibiotic-associated C difficile infection patients with cirrhosis. thrombin inhibitor Pradaxa (dabigatran). and antibiotic-associated diarrhea in pa- Published online 07-22-2016 scripintelligence.com 29 July 2016 | Scrip intelligence | 19 EXPERT VIEW
Bounce Or More Bumps? New China Market Data Offer Bit Of Both Two new sets of data on growth in China’s turbulent pharma sector paint a mixed and complex picture, indicating both challenges and opportunities ahead for multinational and domestic firms in the country. BRIAN YANG [email protected]
ow healthy is the pharma industry in China really? According GREEN SHOOTS? to the latest official data, overall growth for the drug manu- But despite these quarterly trends of a slowdown in China’s overall Hfacturing sector is continuing to slow, declining to 9.6% in pharma industry, there are signs that growth is slowly returning to the calendar first quarter of this year, down from 9.8% in the whole both the multinational and domestic prescription drug sector in the of 2015 and from 10.7% in the same quarter of last year. country. In a July 8 report released via its WeChat social media plat- While these figures remain high compared with many other ma- form in China, IMS China said that overall, MNCs grew by 10.2%, and jor markets, the new quarterly data released on July 12 by China’s domestic firms by 9.1%, in the first three months. Ministry of Industry and Information Technology (MIIT) painted an Overall hospital market sales were CNY169bn in the three-month increasingly sluggish picture for pharma, although certain subsec- period, up 9.3% compared to the same quarter of last year, IMS said. tors including medical devices performed more strongly than both IMS’s data is based on its proprietary prescription drug sales tally chemical and biologic drugs. from Chinese hospitals with over 100 beds, a different method of The first quarter has traditionally been slow due to the week-long calculation from the MIIT data, which are collected from drug mak- Chinese Lunar New Year holiday, which dampens demand, but the ers’ revenues and profits, and which leads to discrepancies in the start of 2016 has been particularly challenging, dragged down by growth figures. policy headwinds and pricing pressures. Figures compiled by PharmAsia News meanwhile showed that Among these factors, notable is a recent policy from the National major MNCs on average grew by 8% in China in the first quarter, Health and Family Planning Commission to slash hospital spending down from the 11% achieved in the whole of 2015, again painting by half, which is likely to hurt pharma sales growth going forward. a picture of slowing growth. Despite the challenges though, some specific areas performed Foreign multinationals Pfizer Inc, and AstraZeneca PLC and do- better than others, with the fastest-growing being medical device mestic group Qilu Pharmaceuticals Co. Ltd topped the list of IMS’s manufacturing, up 14%, followed by traditional Chinese medicine major drug firms in Q1, followed by Yangtze River Pharma, Sihuan tablets. Chemical drugs and biologics meanwhile rose by a rela- Pharma and Sanofi. tively low 9.5% and 9.6% respectively, the MIIT data show. GROWTH OPPORTUNITIES $133BN INDUSTRY But where is the growth for such companies coming from? The IMS Overall, the ministry’s figure for total revenues for the pharma indus- report pointed to smaller cities for multinationals and China’s mega- try (including devices) reached CNY867bn ($133bn) for the quarter, cities for domestics. and it put the aggregate profit of the sector at CNY57.6bn (+9.8%). “The two have a different competitive landscape. Domestics are The active pharmaceutical ingredient (API) area increased its profit- over-growing MNCs in the tier 1 [major] city market, while MNCs ability the most, up 38% and well ahead of the figures for finished are grow faster in lower-tier market,” IMS noted. chemical drug manufacturing and biologics, which came in at 15% The lower level county hospital sector has been a strong growth and 5% respectively. Pharma equipment manufacturing meanwhile driver for multinationals such as AstraZeneca and Sanofi, with the saw its combined profits dip by 3%. latter firm recently kicking off a major new initiative to enter China’s API makers with a heavy reliance on exports are benefiting from urban health clinic market. a weakening Chinese currency, which has depreciated by 6% from Still, the broader economic slowdown, and downward pressure last year’s CNY6.2 to the US dollar to nearly CNY6.6 currently. Chi- on drug prices and spending, in China is continuing to weigh on nese customs data show that overall medical product exports in- drug companies. The IMS data show that product sales in several creased by 2.7% in 2015, reaching $56.4bn. therapeutic areas were disappointing. In particular, oncology, an- There were also worsening signs of growth in total pharma in- tibiotics, traditional Chinese medicines (TCMs) and intravenous in- dustry investment, which had already been declining during the jections encountered strong policy headwinds, and sales declined course of 2015 and was down by 3% in the first quarter. significantly, while chronic disease treatments including cardiovas- Since 2010, when China’s 12th Five-Year Plan for economic devel- cular, hypertension and blood thinning drugs fared better, noted opment was rolled out, drug makers have been investing heavily in its report. new factory construction and the upgrading of current facilities, in The top-selling products are the TCM Shenjie, Plavix (clopidogrel) a bid to meet the requirements of GMP standards. But now, with and Xueshuantong (another TCM), followed by Lipitor (atorvastatin), the efforts towards GMP implementation now largely completed, Pulmicort (budesonide) and the TCM Beitong. this upward investment trend is waning, according to the latest Published online 07-19-2016 MIIT data. From the editors of PharmAsia News.
20 | Scrip intelligence | 29 July 2016 © Informa UK Ltd 2016 STOCKWATCH
Earnings Season Appears Not At Home To Brexit On the morning of the vote by the UK to leave the EU, I speculated firstly that the ensuing currency swings would come too late to impact the imminent second-quarter pharma earnings announcements but secondly, that they could have an effect on the guidance of companies for the rest of the year. In the opening week of earnings season I am currently one for two in the prediction stakes as the effects of Brexit barely figured in either the results or the full-year guidance. ANDY SMITH
ovartis AG beat Johnson & John- meating through the early part of this results 0.5% on the day. J&J reported stronger results son (J&J) into second place by a season. Ironically, Novartis is a past master than Novartis with sales and earnings that Nfew hours in being the first big life at benefiting from delayed competition to beat analysts’ consensus estimates by 3% and sciences company to report second-quarter its hypertension franchise: manufacturing 5%, respectively. Like Novartis, J&J raised full- earnings. Novartis’ sales and earnings beat problems at Ranbaxy Laboratories delayed a year earnings guidance but also like Novartis analysts’ consensus estimates by 2% and generic to its hypertension drug and Entres- there was an aspect that seemed to be un- 3%, respectively. As usual there was a strong to component Diovan (valsartan) until the derplayed and absent from the notes I read performance from its pharmaceutical and expiry of the 180-day exclusivity period. This from the analysts at Cowen and UBS. J&J’s also (going against recent history), at its ge- benefit from delayed generic competition by results were flattered by a one-off $170m nerics division Sandoz, Inc. The hoped for either the mistakes of other companies (in gross-to-net adjustment that comprised turnaround at the eye care division Alcon Novartis’ case), or a dragging of feet on licens- 76% of the beat of its best-performing phar- had largely still not materialized. When I read ing Tracleer’s (bosentan) REMS program (in maceutical division. J&J’s upward guidance Novartis’ earnings announcement, I thought Actelion’s), or even the unsuccessful attempt revision therefore seems quite fragile since it that the results were good against my expec- to hang a new orphan exclusivity period on incorporates the effect of last quarter’s one- tations of a Brexit-induced guidance down- the out of patent statin Crestor (rosuvastatin) off gross-to-net revision, a lower quarterly tax grade and although its full-year guidance (by AstraZeneca PLC ) seems to have lost rate and the absence of Remicade (infliximab) was lowered slightly, it was on the basis of some currency with investors. Like Novartis, biosimilar competition. Novartis’ increased primary care investment despite reporting good results last week, the In the opening salvos of second-quarter on Entresto (sacubitril/valsartan) for heart Actelion share price finished just into positive earnings season the life science sector seems failure after its elevation in recent guidelines. territory on the day of its announcement. to have gotten off lightly with the absence Since our fund holds neither Novartis nor With a company as big and diverse as No- of any material Brexit effect and a delay to J&J I started to wonder if I had missed out this vartis, it is always possible to find something both small molecule and biosimilar compe- earnings season’s early highlights. However, to critique in a quarterly results announce- tition. In those respects, it is just too early to on that day the Novartis stock price finished ment and although the FDA’s complete make a judgement on the sector’s quarter about where it started. When I read analysts’ response letter for Sandoz International or year yet. One hard conclusion I did take reportage on Novartis’ results, I began to de- GMBH’s biosimilar of Amgen Inc. ’s Neulasta away from last week concerned the nearly tect a nonplussed stance. The analysts at Citi- (pegfilgrastim) was certainly unwelcome, its 7% share price rise on the announcement group entitled their note “2Q Good Enough” low profile in Novartis’ results was perhaps a of Biogen, Inc’s. second-quarter results. Most but described the results as “robust,” Entresto bigger component of the lackluster response of Biogen’s products saw quarterly sales in- sales were $32m, missing consensus esti- to the results announcement. The analysts at creases. However, the cognoscenti know that mates of $35m. This is a disappointing launch JP Morgan described the 5% generic price most of those increases were due to the two in big pharma terms and the specter of this erosion at Sandoz as “supportive of relative price increases that Biogen has imposed so great white hope product for Novartis never stability in the generic pricing environment far this year. I prefer the explanation that after meeting its lofty expectations may have been for the large, diversified manufacturers.” I tend a mixed tenure, investors were happy to see part of the Citigroup analysts’ caution. Their to disagree since the generic pricing model the back of its CEO whose retirement was an- lack of enthusiasm was mirrored by the ana- is built upon the yin of new generic product nounced along with Biogen’s results. lysts from JP Morgan, whose note was entitled launches (with hopefully 180 day, first-to-file Andy Smith is chief investment officer of “2Q16 Results First Take: Good Enough” and exclusivity periods) against the more recent Mann Bioinvest. Mann Bioinvest is the invest- attributed Novartis’ performance to a lower yang of generic price deflation. The fact that ment adviser for the Magna BioPharma In- than expected Gleevec (imatinib) generic generic price deflation is now recurring with come fund which has no position in the stocks erosion – ironically a theme that also helped -5% declines happening all year every year mentioned, unless stated above. Dr Smith Swiss compatriot Actelion Pharmaceuticals means that eventually the pure-play generic gives an investment fund manager’s view on Ltd. when it reported later in the week. pharmaceutical company will not have the life science companies. He has been lead fund With the new threats of drug pricing sen- earnings growth trajectory that investors de- manager for four life science–specific funds, in- sitivity and biosimilar competition that phar- mand from this sector. cluding International Biotechnology Trust and maceutical and biotechnology companies J&J’s second-quarter results had a similar the AXA Framlington Biotech Fund, and was face, it was somehow reminiscent to find initially positive feel to those of Novartis, ex- awarded the Technology Fund Manager of the the old classic threat of generic expiry per- cept that its share price finished up about year for 2007. Published online 07-25-2016
scripintelligence.com 29 July 2016 | Scrip intelligence | 21 PIPELINE WATCH
Scrip’s weekly Pipeline Watch tabulates the most recently reported CLICK late-stage clinical trial and regulatory developments from the more Visit scrip intelligence.com than 10,000 drug candidates currently under active research worldwide. for the entire pipeline with added commentary. Late-stage clinical developments for the week 15–21 July 2016
LEAD COMPANY PARTNER COMPANY DRUG INDICATION MARKET REGULATORY APPROVAL Qtern (saxagliptin plus AstraZeneca PLC – type 2 diabetes EU dapagliflozin) tablets SUPPLEMENTAL REGULATORY APPROVAL Valeant Pharmaceuticals Progenics Relistor (methylnaltrexone opioid-induced constipation US International Inc. Pharmaceuticals Inc. bromide) oral tablets Celgene Corp. – Revlimid (lenalidomide) mantle cell lymphoma EU Pharmacyclics Janssen Inc. Imbruvica (ibrutinib) chronic lymphocytic leukemia Canada Inc. (AbbVie Inc.) Arena Pharmaceuticals Belviq XR (lorcaserin) Eisai Co. Ltd. obesity US Inc. once-daily tablets Eisai Co. Ltd. – Halaven (eribulin) sarcoma Russia CSL Behring – Berinert (C1 esterase inhibitor) hereditary angioedema attacks US Janssen Pharmaceuticals – Prezista (darunavir) HIV in pregnancy US Inc. REGULATORY FILING ACCEPTED Mylan Pharmaceuticals Inc. Biocon Ltd. pegfilgrastim biosimilar neutropenia EU Lexicon Ipsen telotristat etiprate neuroendocrine tumors EU Pharmaceuticals Inc. Merck KGAA - cladribine tablets multiple sclerosis EU Samsung Bioepis rheumatoid arthritis, ankylosing spondylitis, Co. Ltd.(Samsung Merck & Co. Inc. adalimumab biosimilar (SB5) psoriasis, psoriatic arthritis, Crohn’s disease, EU BioLogics andBiogen) ulcerative colitis SUPPLEMENTAL REGULATORY FILING ACCEPTED Bristol-Myers Squibb Co. – Opdivo (nivolumab) head and neck cancer EU, US ORPHAN DRUG DESIGNATION Incyte Corp. Eli Lilly & Co.,Novartis AG Jakafi (ruxolitinib) acute lymphoblastic leukemia US Xoma Corp. – XOMA 358 congenital hyperinsulinemia EU Alcobra Ltd. – metadoxine extended-release Fragile X syndrome EU COMPLETE RESPONSE LETTER Novartis AG – pegfilgrastim biosimilar neutropenia/leukopenia US SequestOx (oxycodone and Elite Pharmaceuticals Inc. – acute pain US naltrexone) REGULATORY FILING Puma Biotechnology Inc. - neratinib early-stage breast cancer US ROLLING NDA FILING INITIATED Novartis AG – midostaurin (PKC412) mastocytosis and acute myeloid leukemia US REGULATORY REVIEW EXTENSION Merck & Co – bezlotoxumab Clostridium difficile-associated diarrhea US PRODUCT LAUNCH Takeda Pharmaceutical Moviprep (polyethylene glycol Norgine BV bowel preparation before surgery Russia Co. Ltd. and electrolytes) Invokamet (canagliflozin and Janssen Inc. - type 2 diabetes Canada metformin) Fujifilm Pharma Co. Ltd. Biocon insulin glargine biosimilar type 1 diabetes Japan Source: Sagient Research’s BioMedTracker
22 | Scrip intelligence | 29 July 2016 © Informa UK Ltd 2016 APPOINTMENTS
Lannett has promoted Kristie Stephens Corporation, Cyplasin Biomedical, Alethia with over 20 years’ of experience. Currently, to vice president of regulatory affairs and BioTherapeutics and Bioaxone Therapeutics. he is director of the diabetes unit the In- chief compliance officer and John Ko- stitute of Endocrinology, Metabolism & zlowski vice president financial operations Boston Pharmaceuticals has appoint- Hypertension, Tel-Aviv Sourasky Medical and corporate controller. Stephen joined ed Ian Sanderson chief financial officer. Center. Prior to this, Eldor was principal sci- Lannett in 1999 as a chemist and prior to Sanderson comes to Boston from Ca- entist at Merck Research Laboratories, clini- this promotion, she was the company’s tabasis Pharmaceuticals where he was cal research, diabetes and endocrinology. director of regulatory affairs. Kozlowski chief financial officer, prior to this he was Previously he was senior physician in inter- joined Lannett in 2009 and most recently senior advisory with JSB Partners where nal medicine at the diabetes unit in Hadas- was corporate controllers and prior to advised life science companies on cor- sah Hebrew University Hospital, Jerusalem, joining this company, he served in senior porate finances, M&A and business de- Israel; the diabetes division at the University finance and accounting roles for Optium velopment transactions. of Texas Health Science Center in San An- Corporation and Finisar Australia. tonio, Texas. Gradalis, Inc. has appointed Martin Birk- VBI Vaccines Inc. has appointed Francis- hofer Sr. vice president and chief medical BTG Plc., a specialist healthcare company, co Diaz-Mitoma chief medical officer. Most officer. Most recently Birkhofer was chief has appointed Graham Hetherington recently he was professor of the Northern medical officer at NuCana BioMed Limited non-executive director of the board and Ontario School of Medicine and he was vice and prior to this he held the same position chair of the audit committee – Aug. 1, president of research at Health Sciences at inVentiv Health Clinical. From 1994 and 2016. Previously he was chief financial of- North and founder of the Advanced Medi- 2013 he held various leadership roles at ficer of Shire Plc. from 2008 to 2014, Bacardi cal Research Institute of Canada (AMRIC) Bristol-Myers Squibb including vice presi- in 2007 and Allied Domecq Plc. from 1999 and served as its CEO and chief scientist. dent search, evaluation and diligence, vice to 2005. He is a fellow of the Chartered In- president oncology global medical affairs, stitute of Management Accountants. Acreus Pharmaceutical Corporation vice president product development for has appointed Luc Mainville to its board Erbitux, executive director of oncology Biostage Inc., a biotech developing bio- of directors, the audit committee and will clinical research Europe and executive di- engineered organ implants to treat cancers also serve as chair. Mainville is currently ex- rector clinical pharmacology. and other life-threatening conditions, has ecutive vice president at Cardiome Pharma appointed Harout DerSimonian chief Corp. and previously served as president and Oramed Pharmaceuticals Inc. has ap- scientific officer. With more than 20 years’ CEO of Neopharma Labs Inc. He also served pointed Roy Eldor to the newly created experience DerSimonian is a former assis- as chair of the audit committee for various position of chief medical director. Eldor is tant professor and post-doctoral fellow at boards including Enobia Pharm, Powertech an endocrinologist, internist and researcher Harvard Medical School. Scrip ELEANOR MALONE @SCRIPELEANOR IAN SCHOFIELD @SCRIPIANS JOHN DAVIS @JOHN023DAVIS [email protected] [email protected] [email protected] ALEXANDRA SHIMMINGS @SCRIPALEXS ASHLEY YEO @ASHLEYPYEO SARAH WEIR @SCRIPSARAH [email protected] [email protected] [email protected] SUKAINA.VIRJI @SCRIPSUKI LISA LAMOTTA @BIOWRITERCHIK All stock images in this publication [email protected] [email protected] courtesy of www.shutterstock.com ANJU.GHANGURDE @SCRIPANJUG LUCIE ELLIS @SCRIPLUCIE unless otherwise stated. [email protected] [email protected] Customer Services DONNA YOUNG @SCRIPDONNADC LUBNA AHMED @SCRIPLUBNA Tel: +44 (0)20 7017 5540 [email protected] [email protected] or (US) Toll Free: 1 800 997 3892 MANDY JACKSON @SCRIPMANDY PAUL WILKINSON @PAUL__WILKINSON Email: [email protected] [email protected] [email protected] To subscribe, visit JOANNE SHORTHOUSE @SCRIPJO JOHN HODGSON @SCRIPJOHN scripintelligence.com [email protected] [email protected] To advertise, contact FRANCESCA BRUCE @SCRIPFRANCESCA MIKE WARD @SCRIPMIKEWARD [email protected] [email protected] [email protected] Scrip is published by Informa UK Limited. STEN STOVALL @STENSTOVALL PETER CHARLISH @PETERCHARLISH ©Informa UK Ltd 2016: All rights reserved. [email protected] [email protected] ISSN 0143 7690.
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