Author: Jean-Claude Muller, 穆卓Executive Editor at BtoBioInnovation, jcm@btobioinnovation.com

Zika virus

Zika epidemic outbreak has officially be declared in French Guadeloupe, on April 30, where 2,100 infected people have been identified. French officials indicated that “over the last weeks they saw a dynamic acceleration of the spreading of the disease which justify to declare the epidemic outbreak”

An International Zika Summit took place earlier this week, at the Institut Pasteur (Paris), to assess the risk of a Zika outbreak in continental Europe. The experts concluded that Aedes aeggypti, already present on Madeira Island is more prone to be a vector of the disease than Aedes albopictus present in southern parts of Europe.

Athletes and coaches fear Zika infections at the Rio Olympic Games.

The questions are particularly acute for those planning to have children now that health officials confirmed that Zika causes microcephaly and other severe brain abnormalities and can spread through sexual contact. Current guidelines from the Centers for Disease Control and Prevention recommend that a woman returning from a Zika-prone region wait about eight weeks before trying to conceive, in case she has an asymptomatic infection. Men “need to practice safe sex for at least two to six months after coming back, based on what we know today. The sexual-transmission question has made it much more complicated because you’re now viewing men as vectors of spread to pregnant women anywhere.”

Acquisitions /mergers/joint-ventures

Sanofi has made an offer to acquire Medivation (South San Francisco, CA, USA) in an all cash deal valued at $9.3 billion. Under the terms disclosed, Sanofi has offered $52.50 a share but Medivation’s Board has rejected the offer on Friday saying it “undervalues” the company. The bid could now become hostile. According to Credit Suisse Medivation is worth $55 a share and was traded above $56 most of the day on Friday. Other potential companies such as AstraZeneca, Celgene and Roche may also enter the bid. The increased attention for this acquisition comes from the recently reported strong sales of Xtandi, or enzalutamide, a prostate cancer drug, which reached $1.15 billion in the US in 2015, and the potential of talazoparib, a late-stage PARP inhibitor, for the treatment of various cancers.

Abbvie continues to boost its oncology portfolio. Just one week after announcing deals with argenx and the University of Chicago, AbbVie acquires Stemcentrex (South San Francisco, CA, USA) for $5.8 billion in cash and stocks and potential additional success contingent milestones worth another $4 billion. Stemcentrx’ main asset is rovalpituzumab tesirine, an antibody drug conjugate targeting the cancer stem cell protein DLL3, which is highly expressed in small cell lung cancers, but the company also has four early-stage clinical compounds for the treatment of solid tumours.

… and strikes a $500 million deal with CytomX (South San Francisco, CA, USA) on the development of Probody drug conjugates against CD71, also known as transferrin receptor-1. CytomX has generated preclinical data that demonstrate that Probody drug conjugates bind selectively to tumors and avoid binding to healthy tissue and that they can therefore safely and effectively target tumor antigens, such as CD71, that are not addressable by conventional antibody-drug conjugates. Under the terms of the deal AbbVie will make an upfront fee of $30 million and additional milestones payment of up to $470 million.

According to the Swiss newspaper Die Sonntagszeitung, Novartis is considering selling off its stake in Roche worth nearly $14 billion with the clear desire to use the investment for more strategic purposes. Both companies have so far declined to comment…

Abbott is acquiring St Jude Medical (St Paul, Min, USA) in a $25 billion deal and intends to become “a premier medical device leader with top positions in high-growth cardiovascular markets, including atrial fibrillation, structural heart and heart failure as well as a leading position in the high-growth neuromodulation market”. With combined annual sales of approximately $8.7 billion, Abbott's cardiovascular business and St. Jude Medical will hold leading positions across the growing cardiovascular device markets. Under the terms of the deal, Abbott will pay $46.75 in cash and 0.8708 shares of Abbott common stock, representing a total value of $85 per share.

…and wants to walk away from Alere. In February, Abbott said it would buy Alere for $5.8 billion to "create the world's premier point of care testing business" and to "significantly strengthen and grow" its testing presence. But now with all the alleged problems about Alere’s state of affairs, Abbott wants to get out and has offered $50 million in cash to call out. Alere "promptly rejected that request and remains completely confident that there is no basis for a termination of the merger agreement"

Nokia acquires Withings (Paris, France), a pioneer and leader in the connected health business with family health products and services, in a deal worth $170 million. Through the agreement, Nokia will get access to a large med tech portfolio, including activity trackers, weighing scales, thermometers, blood pressure monitors and home monitors.

Business

AstraZeneca announces three deals:

A licensing deal with Ironwood Pharmaceuticals (Cambridge, MA, USA) which secures exclusive US rights to AstraZeneca’s Zurampic or lesinurad, approved by the US FDA in December 2015, for the treatment of hyperuricemia. Under the terms of the agreement, Ironwood will pay an upfront payment of $100M, milestones up to $165M and tiered single-digit royalties and AstraZeneca will supply lesinurad’s API and finished dosage form.

A collaboration with TapImmune (Jacksonville, FL, USA) to assess the value of the combination of AstraZeneca’s durvalumab, an investigational human monoclonal antibody directed against PD-L1, with TapImmune’s cancer vaccine TPIV, a multi-epitope anti-folate receptor vaccine (FRα), for the treatment of platinum-resistant ovarian cancer.

…and a collaboration with three partners: the Wellcome Trust Sanger Institute in the UK, The Institute for Molecular Medicine, in Finland and with the Human Longevity in the US to sequence up to two million genomes in a bid to identify genetic mutations that drive disease of interest.

Sanofi Genzyme announces a drug discovery deal with Recursion Pharmaceuticals (Salt Lake City, UT, USA) aimed at generating new candidates for certain genetic disease. Recursion uses high-throughput experimental biology to model diseases and informatics to identify specific changes associated with each disease model to identify the "phenoprint" and to evaluate the ability of drug candidates to restore the disease-specific changes back to normal. Sanofi will provide a set of small molecules to be screened by Recursion and secure the option to develop promising candidates. Financial terms were not disclosed.

GlaxoSmithKline enters a collaboration with Zymeworks (Vancouver, Canada) to develop and market bispecific antibodies using the Azymetric™ drug discovery technology in a deal worth up to $908 million. Back in December GSK had already establish a collaboration with Zymeworks on Fc-engineered monoclonal and bispecific antibodies through the Effector Function Enhancement and Control technology (EFECT™) platform. This new agreement allows GSK to combine the Azymetric™ platform with novel engineered Fc domains developed through EFECT™. Under the terms of the deal GSK will pay $36 million upfront and as much as $872 million in various milestone fees plus sales royalties.

Approval of drugs and vaccines

The European Commission approves:

Eli Lilly’s Talz, or ixekizumab, an interleukin-17 antibody, as a new treatment for moderate-to-severe-plaque psoriasis. The drug had been approved by the US FDA two months ago.

…and Servier’s (Paris, France) Lonsurf as a treatment of certain patients with metastatic colorectal cancer.  Lonsurf combines an anticancer drug trifluridine, which interferes with DNA function, with tipiracil which maintains adequate blood concentration of trifluridine. The drug was approved by the US FDA last September and is commercialized by Taiho Oncology (Princeton, NJ, USA)

US FDA approves:

Exelexis (South San Francisco) Cabometyx, or cabozantinib, a C-MET and VEGFR2 kinase inhibitor, for the treatment of advanced renal cell carcinoma in patients who have been treated with prior angiogenic therapy.

AstraZeneca’s Bevespi Aerosphere, a twice-daily, fixed-dose dual bronchodilator combining glycopyrrolate, a long-acting muscarinic antagonist and formoterol fumarate, a long-acting beta-2 agonist in a single inhaler for the treatment of chronic obstructive pulmonary disease. Bevespi Aerospher is the first product approved that employs the novel co-suspension technology.

….and Watson Pharmaceuticals rosuvastatin calcium, as the first generic version of AstraZeneca’s Crestor which had peak sales of over $5 billion

But rejects Otsuka/Proteus’ Digital Medicine – a drug/device including antipsychotic Abilify within Proteus’ ingestible sensor – for the treatment of psychiatric disorders.  In the complete response letter the FDA required additional data, including the performance of the product under the conditions in which it is likely to be used, and further human factors investigations.

Drugs at clinical stage

US FDA grants breakthrough status to:

Novartis’ Ilaris or canakinumab for three rare conditions: Tumor Necrosis Factor-Receptor Associated Periodic Syndrome Hyperimmunoglobulin D Syndrome Mevalonate Kinase Deficiency and Familial Mediterranean Fever patients not adequately controlled with colchicine. Canakinumab is a human monoclonal antibody that binds to the pro-inflammatory protein interleukin-1 beta and was approved in the US, in 2009 for the treatment of a rare autoinflammatory condition called Cryopyrin-Associated Periodic Syndromes and, in 2013, for the treatment of a rare form of juvenile idiopathic arthritis.

… and to Bristol-Myers Squibb’s Opdivo for the treatment of recurrent or metastatic cell carcinoma of the head and neck. The recommendation comes just one week after BMS has reported that patients treated with Opdivo compared to patients treated with methotrexate, docetaxel, or cetuximab, experienced a 30 % reduction in the risk of death, with a median overall survival of 7.5 months versus to 5.1 months.

US FDA grants fast track to Advaxis’ (Princeton, NJ, USA) ADXS-HER2, as a treatment for osteosarcoma. ADXS-HER2 is an Lm Technology™ immunotherapy product targeting HER2 expressing cancers. Lm Technology™ products alter a live strain of Listeria monocytogenes bacteria to generate cancer fighting T-cells directed against a cancer antigen and neutralizing factors that protect the tumor microenvironment

China's Center for Drug Evaluation will put hepatitis C drug candidates on a fast track review, setting the stage for approvals in the near term for several new drugs from Gilead, Bristol-Myers Squibb and Ascletis Pharmaceuticals (Shaoxing, China)

Medical Devices and Diagnosis News

US FDA now proposes banning the use of electric shocks that are employed to treat children who are aggressive or prone to harming themselves. “Our primary concern is the safety and well-being of the individuals who are exposed to these devices,” said Dr. William Maisel, acting director of FDA’s Office of Device Evaluation. “These devices are dangerous and a risk to public health. We believe they should not be used.” The devices work by delivering shocks via electrodes attached to the skin. Proponents of the shock devices argue that they have proven to be an effective means of changing destructive behavior by children and others with development disabilities. At an FDA advisory committee session on the issue in 2014, Glenda Crookes, at the time, the Judge Rotenberg Educational Center’s (Canton, MA, USA) executive director, defended the devices as safe and effective. But now the FDA said it believes “state-of-the-art behavioral treatments, such as positive behavioral support and medications, can enable health care providers to find alternative approaches for curbing self-injurious or aggressive behaviors in their patients.”

Apple launches its new CareKit platform with four applications targeting the management of diabetes, depression and maternal/baby health. CareKit complements the already existing physical activity tracker HealthKit and health data sharing platform ResearchKit.

Science and Technology

In a recent study published in Cell, Eric Topol, Director of the Scripps Translational Science Institute (La Jolla, CA, USA), investigated genetic and biological conditions of healthy aging in a group of people he called the “Wellderly”. What did set the Wellderly apart from elderly people with chronic diseases was not so much a correlation between them and the already identified genes contributing to longevity but a set of genes related to their cognitive function. The study did not find a silver bullet for healthy longevity but signals of rare variant sites which collectively suggests that protection against cognitive decline contributes to healthy aging. Topol says it is likely that for healthy aging, it’s necessary to both have genes that lower risk of chronic disease as well as having genes that confer some type of protection against the damaging effects of chronic illness “There are probably hundreds of protective variants” he says.

Researchers from the University of Copenhagen (Denmark) have created a user-friendly platform for the development of effective and safe vaccines which is published in latest issue of Journal of Nanobiotechnology entitled Bacterial superglue enables easy development of efficient virus-like particle based vaccines. The platform consists in mimicking the structure of a virus used as a platform onto which are glued parts of the pathogenic organisms which one wishes to vaccinate against. The simple technique could pave the way for effective vaccines against not only infectious diseases but also cancer and other chronic diseases.

Cost, Pricing and Market Access

The UK National Institute for Health and Care Excellence (NICE) recommends:

Novartis’ Entresto to treat heart failure patients whose disease is not managed by angiotensin receptor antagonists or angiotensin-converting enzyme inhibitors. A yearly treatment in with Entresto, in the UK, comes at $1,750, a third of the price of the drug in the US.

….And Novartis’ oral combination therapy of Tafinlar, or dabrafenib (an inhibitor of the associated enzyme B-Raf) and Mekinist or trametinib (a MEK inhibitor), for the treatment of adults with unresectable or metastatic melanoma with a BRAF V600 mutation. Patients with advanced melanoma have a life expectancy of under two years. “This combination treatment is the latest in a line of promising new drugs for advanced melanoma we have recommended that look set to significantly extend the life of people with the condition,” said Professor Carole Longson, Health Technology Evaluation Centre Director at NICE. The NHS will pay a reduced price for the drugs after a confidential discount was agreed between Novartis and the Department of Health, but the list price per patient per 28 days in the UK is £10,080.

German health ministry indicated that it will draw up new plans to limit prices for new drugs and halt the ongoing lucrative pricing amnesty. The current system in place allows healthcare insurers to negotiate discounted prices with pharma companies on their new drugs but allow them to pay full price up to a year from the time they were approved.

Miscellaneous

An international study published in the Lancet concluded that Chantix/Champix (varenicline) from Pfizer and Zyban (buproprion) from GlaxoSmithKline, two smoking cessation drugs, did not significantly increase the risk of serious neuropsychiatric adverse effects when compared to placebo or a nicotine patch in 8,144 adult smokers, around half of which had a history of psychiatric disorders.

Biogen appoints Michael Ehlers as its new R&D head effective end of May. He joins from Pfizer where he was in charge for Biotherapeutics R&D and CSO for the Neuroscience and Pain Research Unit.

Enjoy the 1st May and the Golden Week Holiday.

Bioevents

Bio€quity Europe 2016 on May 10-11 in Copenhagen (Denmark)

Strategic Alliance Management Congress on May 16-18 in Philadelphia (USA)

China BIO Partnering Forum on May 18-19 in Suzhou (China)

4^th Annual IBA World Life Sciences Conference on June 3-4 in San Francisco (USA)

BIO International Convention on June 6-9 in San Francisco (USA)

BIO Pharm America on September 13-15 in Boston (USA)

7^th Innovation Days on October 3-4 in Paris (France)

BIO Europe on November 7-9 in Cologne (Germany)

BIO Latam on November 29-30 in San Juan (Puerto Rico)

Biofit 2016 on November 30-December 1 in Lille (France)

IMPORTANT NOTICE

This document has been prepared by btobioinnovation and is provided to you for information purposes only.  The information contained in this document has been obtained from sources that btobioinnovation believes are reliable but btobioinnovation does not warrant that it is accurate or complete. The views presented in this document are those of btobioinnovation’s editor at the time of writing and are subject to change.  btobioinnovation has no obligation to update its opinions or the information in this document.