Biopharmaceutical News Week 15- 2016

Zika virus

US Centers for Disease Control and Prevention (CDC) confirmed earlier studies by a French team that infection with the Zika virus in pregnant women is a cause of birth defects and other severe brain abnormalities in babies “There isn’t any doubt that Zika causes microcephaly” said CDC’s Director Tom Frieden . CDC also indicated that the type of mosquito in which the virus is carried is present in wider number of US states and the revelation “is scarier than we thought”.

US President Barack Obama will sign a bipartisan bill that would add Zika virus treatments to a list of diseases that qualify for a priority review by the FDA and would also provide incentives to companies seeking cures for the Zika virus. “The passage of that bill is positive, but a rather meager accomplishment,” White House press secretary Josh Earnest told reporters. “In some ways, it’s akin to passing out umbrellas in advance of a hurricane.” The spokesman said Congress is “two months late and $1.9 billion short” of what’s needed to stop the spread of the virus, referring to Obama’s emergency funding request, which is stalled in Congress.

Acquisitions /mergers/joint-ventures

Madrigal Pharmaceuticals (Fort Washington, PA, USA) and Synta Pharmaceuticals (Lexington, MA, USA) have agreed to merge to form a company specializing in the development of small-molecule drugs for non-alcoholic steatohepatitis (NAS) and cardiometabolic disorders.

According to “people familiar with the matter” Medivation (South san Francisco, CA, USA) has turned down Sanofi’s recent takeover offer. Sanofi has not ruled out making a hostile bid. Medivation which focuses on difficult to treat cancers is seeking a higher price than the initial proposal by Sanofi and/or expecting an offer by other suitors. Medivation recently got European approval for its Xtandi drug, as a treatment of prostate cancer and has two other drugs, pidilizumab for the treatment of large B cell lymphoma and talazoparib, for the treatment of breast cancer in late stage clinical development.

According to Reuters Lonza, the Swiss contract manufacturing organisation, has put in an offer to acquire drug manufacturer and delivery firm Catalent.

Business

Celgene has exercised its option to develop and commercialise Juno Therapeutics’ (Seattle, WA, USA) CD-19 chimeric antigen receptor technology (CAR-T) product candidates outside North America and China. Under the terms of the deal Celgene will pay a $50 million fee and royalties in the mid-teens on sales made by Celgene in its territories. Celgene and Juno had launched a ten years global collaboration last year to develop and commercialise cancer and autoimmune diseases immunotherapies, focusing on CAR-T as well as T-cell receptor (TCR) technologies.

Regeneron Pharmaceuticals (Tarrytown, NY, USA) and Intellia Therapeutics (Cambridge, MA, USA) enter into a six-years partnership to discover, develop and market novel therapies for up to ten targets using Intellia’s CRISP-Cas gene editing platform technology. Regeneron will pay $75 million upfront and “significant” payments on achieved milestones and royalties on sales.

Tobira Therapeutics (South San Francisco, CA, USA) signs two exclusive license deals with Dong-A ST (Seoul, South Korea). The first deal consists in acquiring evogliptin, in combination with cenicriviroc as a single agent for various indications, in the US, Canada, Europe and Australia. Under the second agreement Dong-A secures exclusive rights to develop and market cenicriviroc, as a single agent and in combination with evogliptin, for all indications in Korea. Evogliptin is Dong’s antihyperglycemic agent. Cenicriviroc is a dual inhibitor of CCR2 and CCR5, two proteins involved in inflammation and fibrosis processes, which is under development for non-alcoholic steatohepatitis (NASH) and insulin sensitivity.

Astellas (Tokyo, Japan) is in talks with Kaketsuken (Kumamoto, Japan) over selling its vaccine business. Earlier this year Japan’s Ministry of Health, Labor and Welfare (MHLW) had suspended Kakestuken for 110 days after it found that the company was using unauthorized methods to make vaccines and blood products for more than 40 years. Kaketsuken vaccine portfolio includes products for hepatitis A, hepatitis B, flu and Japanese encephalitis, as well as a quadrivalent vaccine against diphtheria pertussis, tetanus which are distributed by Daiichi Sankyo and Takeda. According to Nikkei, Kaketsuken holds about 30% of the Japanese flu vaccine market.

Biogen (Cambridge, MA, USA) is exploring the sale of its hemophilia treatment portfolio as part of strategy to focus on its core therapeutic areas including neurology and autoimmune diseases. Biogen now has Alprolix and Eloctate approved by the US FDA and its hemophilia drugs produced sales of about $500 million in 2015.

Approval of drugs, vaccines, diagnostics and devices.

US FDA approves AbbVie and Genetech’s Venclexta, or venetoclax, for the treatment of chronic lymphocytic leukemia patients with a 17p deletion. Venetoclax acts as a Bcl-2 inhibitor in blocking the anti-apoptotic B-cell lymphoma-2 (Bcl-2) protein, leading to programmed cell death. The drug has a list price of $109,500 for the first year of treatment and slightly higher for subsequent years.

US FDA set a record by approving 580 generic products and gave tentative approval to 146 products in 2015. Tentative approval refers to generic applications that are submitted for approval before the patent or market exclusivity on a brand-name product expires. That is more than fiscal 2013, when 440 drugs were approved and 95 received tentative approval. The agency now has a goal of acting on a generic drug application within 10 months.

The World Health Organization (WHO) Advisory Group of Experts (SAGE) on Immunization reviewed Sanofi Pasteur’s Dengvaxia and recommended countries consider introduction of the vaccines only in geographic settings (national or subnational) with high endemicity.

Drugs at clinical stage

US FDA grants orphan status to Appili Therapeutics’ (Halifax, Nova Scotia, Canada) ATI-1501, for the treatment of Clostridium difficile in children. ATI-1501 masks the bitter taste of metronidazole, making children more likely to take the medicine.

US FDA grants fast track status to The Medicines Company’s (Parsippany, NJ, USA) Carbavance, an antibiotic containing meropenem, a broad spectrum antibiotic and vaborbactam, a beta lactamase inhibitor, as an intravenous infusion treatment for patients with complicated urinary tract.

US FDA grants priority review status:

To Merck’s Keytruda, or pembrolizumab for the treatment of patients with metastatic or recurrent head and neck squamous cell carcinoma. A decision from the agency is expected by August 9.

to Roche’s MPDL 3280A, or atezolizumab, an anti-PDL1 immunotherapy for patients with PD-L1-positive metastatic or locally advanced non-small cell lung cancer disease. Last month, Roche announced that the FDA had accepted the company’s BLA and granted Priority Review for MPDL 3280A for the treatment of people with locally advanced or metastatic urothelial carcinoma. A final decision from the agency is expected by October 19.

…and to BMS’ Opdivo for the treatment of classical Hodgkin lymphoma. Opdivo was the first PD-1 immune checkpoint inhibitor to receive regulatory approval anywhere in the world in July 2014 and currently has regulatory approval in 48 countries, including the US, Japan and in the EU, for various indications in non-small cell lung cancer, melanoma and kidney cancer. Opdivo has the potential to be the first PD-1 inhibitor in hematology”.

US FDA Oncologic Drugs Advisory Committee (ODAC) voted 12-1 against approving Clovis Oncology (Boulder, COL, USA) rociletinib for the treatment of patients with mutant epidermal growth factor receptor (EGRF) non-small cell lung cancer (NSCL) who have been previously treated with an EGRF therapy and have the T790M mutation. A key issue seems to be the drug’s safety profile with risks such as QTc prolongation leading to “Torsades de pointes”.

Boehringer Ingelheim’s Giotrif or afatinib, outperformed AstraZeneca’s Iressa in a head-to-head study involving patients with EGFR mutation-positive advanced non-small cell lung cancer. Giotrif reduced the risk of disease progression by 27% compared to 15% with Iressa, and, after two years’ treatment, more than twice as many patients taking Giotrif were alive and progression free than those taking Iressa. In addition, Giotrif’s treated patients had an objective tumor response compared to Iressa (70 percent vs 56 percent), with a median duration of response of 10.1 months and 8.4 months, respectively.

Ariad Pharmaceuticals (Cambridge, MA, USA) initiates a Phase 3 clinical trial with brigatinib, an oral inhibitor of anaplastic lymphoma kinase (ALK), for the treatment of patients with ALK positive locally advanced or metastatic non-small cell lung cancer (NSCLC) who have not been previously treated with an ALK inhibitor. The study will compare the efficacy and the safety of brigitinib versus Pfizer’s crizotinib.

Science and Technology

A research team led by Karl Peggs and Sergio Quezada, at the University College London Cancer Institute, have found a way using T-cells without stimulating the entire immune system. The approach consists in gene editing to remove the PD-1 checkpoint from T cells found in a tumor and exposing the cancer cells to the immune system. The recently introduced PD-1 checkpoint inhibitors represent a shotgun approach where healthy cells as well as cancerous cells face an immune response and are therefore rather toxic drugs. The new findings which were reported in Cancer Research are removing the PD-1 switches from T cells from the tumors through a gene editing approach and then multiplying the T-cells without PD-1. When the modified T cells were put back in the mice, their tumors shrank.

Medical Devices and Diagnosis News

A team of scientists and engineers from Case Western Reserve University (Cleveland, OH, USA) has published in Nature Materials the features of a nanostructured optical biosensor for cancer detection that is one million times more sensitive than previous versions." Very early, most circulating tumor cells express proteins of a very low molecular weight, less than 500 Daltons," Pino Strangi, leader of the research said. "These proteins are usually too small and in too low a concentration to detect with current test methods, yielding false negative results. With this platform, we have detected proteins of 244 Daltons. This biosensing platform may help to unlock the next era of initial cancer detection." Strangi and Dr. Nima Sharifi – co-leader of the Genitourinary Cancer Program for the Case Comprehensive Cancer Center – have begun testing the sensor for the earlier detection of prostate cancers

Fractyl Laboratories (Waltham, MA, USA and Barcelona, Spain) gets CE mark for its Revita DMR system a duodenal mucosal resurfacing for metabolic disease including Type 2 diabetes and fatty liver disease. Revita™ DMR is an investigational, minimally invasive, therapeutic procedure designed to remodel the lining of the upper part of the small intestine, or duodenum. It is intended as an outpatient therapy that can be performed in approximately one hour and allows patients to resume normal activities the following day.

Cost, Pricing and Market Access

US drug spending is expected to increase by 12% in 2016 and reach $425 billion.

After receiving a subpoena Valeant’s CEO Pearson agreed to give a deposition to the Senate Special Committee on Aging at a public hearing set for April 27. But the story became tense when Senator Susan Collins, who chairs the committee, and Senator Claire McCaskill said they would move to hold Pearson in contempt for skipping out on an earlier deposition scheduled last week. "We look forward to hearing Mr. Pearson's testimony on April 18" Collins and McCaskill said in a joint statement. "This deposition and investigation are about better understanding the dramatic price increases we're seeing for decades-old prescription drugs and how those prices are affecting consumers–and we're committed to being thorough in that pursuit." Pearson is still scheduled to appear at the April 27 hearing.

Miscellaneous

IBM announces two new Watson Health initiatives. One with the American Cancer Society to apply artificial intelligence to patient-oriented healthcare information, the other to support IBM Health Corps to apply Watson artificial intelligence to solve global health challenges.

Wolfang Kuhne, Roche’s VP of technical development and bioprocessing indicated that the production of a bispecific monoclonal antibody such as ACE910 had required considerable process development effort. The initial steps of making bispecific antibodies are similar to those used to make simple antibodies. The challenge had been the development of novel purification process, because established technologies such as Protein-A based resins had not proved effective.

Bioevents

BIO Trinity on April 25-27 in London (UK)

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)

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.

Author: Jean-Claude Muller, 穆卓Special Advisor at I&IR and Executive Editor at BtoBioInnovation, jcm@btobioinnovation.com

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