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Abstract

Industry Wire

Ceregene (San Diego, CA), started enrollment for a multicenter, double-blind, sham surgery-controlled Phase IIb clinical study for their CERE-120 AAV-based therapy in subjects with Parkinson's Disease. This trial differentiates itself from the completed and published Phase II trial in terms of dosing regimen and the targeting of both substantia nigra and putamen. (lhv)

Genzyme Corp. (Cambridge, MA) still subject to hostile acquisition attempts of Sanofi-Aventis, is contemplating new deal structures that may bring both parties closer to agreement on a purchase price. One plan would make the price contingent on the performance of Campath, a Genzyme drug which is approved for leukemia but currently in testing for multiple sclerosis. (lhv)

GlaxoSmithKline (London, UK), is expanding its research unit to develop drugs for rare diseases that was formed in the beginning of 2010. The latest expansion comprises an alliance with Italian groups of the Fondazione Telethon and Fondazione San Raffaele. The agreement includes an exclusive license to commercialize the experimental lentiviral gene therapy for adenosine deaminase severe combined immunodeficiency (ADA-SCID). The alliance will further develop six additional ex vivo bone marrow derived gene therapy programs. The internal unit of Glaxo focuses on four therapeutic clusters: metabolism and inherited disorders, the central nervous system and muscle disorders, immune-inflammation, hematology and rare malignancies. (lhv)

Oxford Biomedica (Oxford, UK) aims to continue the development of its cancer gene therapy TroVax with a partnering drug firm due to a dwindling cash balance. While the company tries to attract interested parties, it highly anticipates the outcome of studies of ProSavin, a lentiviral gene therapy for Parkinson's Disease (PD). Recently, the final patient was injected in the final and third cohort while it hopes to recruit more patients for a second clinical trial pending approval. The company unsuccessfully applied for orphan disease status with European regulators in order to expedite testing of ProSavin by focusing on patients with advanced disease only. However, regulators saw the treatment as being potentially beneficial for a wider PD patient population, and therefore ruled against the orphan drug designation. In other news, the company received approval from both the FDA and the Recombinant DNA Advisory Committee of the National Institutes of Health to advance RetinoStat, their anti-angiogenic lentiviral gene therapy for treatment of exudative age-related macular degeneration. (lhv)

Pfizer Inc. (Brooklyn, NY) entered a collaborative agreement with the University of California, San Francisco (UCSF) aimed at expediting the discovery of novel medicines and bridging what is often referred to as the ‘Valley of Death’, or the translation of basic research findings into therapeutics. Over the next five years, UCSF can receive up to $85 million. The plan includes the setup of joint laboratories on the university's campus with research teams made up of both UCSF and Pfizer employees. (lhv)

Targeted Genetics (Seattle, WA) and Biocontrol Limited (London, UK) announced a business combination of the two firms. Under terms of the agreement, Targeted Genetics will issue shares of its common stock to the shareholders of Biocontrol. The result will be that Biocontrol is a wholly-owned indirect subsidiary of Targeted Genetics, and Biocontrol's former shareholders will own approximately 50% of the resulting outstanding equity securities of Targeted Genetics. Biocontrol's mission is ‘to develop safe, specific, effective and adaptable biological agents, targeted at markets where current chemical drugs are failing or ineffective.’ Its pipeline is based on bacteriophage technology and has completed initial trials targeting infections of the human ear with the bacterium Pseudomonas aeruginosa. (lhv)

Roche (Basel, Switzerland), the Swiss-based multinational company, announced that it is stepping away from research in RNA interference (RNAi). Roche announced it was killing its program after spending three years and more than $500 million on the technique. The decision is part of a plan to reduce Roche's workforce by 6%, or 4800 people. Roche's announcement came just two months after another Swiss-based company, Novartis, declined to spend $100 million to extend a partnership with Alnylam, a prominent RNAi company based in Cambridge, Massachusetts. There are currently no RNAi drugs on the market; yet, more than a dozen clinical trials are under way in cancer, asthma, and other conditions. (sk)

Regulatory Wire

Biosimilars Make Headlines in Europe and the U.S.

The Biologics Price Competition and Innovation Act (BPCIA), which was included in the healthcare reform law signed by President Obama in March 2010, mandated the FDA to establish a regulatory pathway for approving biosimilars. The new legislation allows for approval of biosimilars after makers of the original biologic have had 12 years of patent exclusivity.

Last month, the Food and Drug Administration held a two-day meeting to gather information on how to implement the new biosimilar approval pathway of BPCIA. Several topics were discussed, and the FDA was charged with balancing several divergent positions on issues such as patient safety and medical costs. At the center of these issues are the standards that the FDA will require for clinical testing of biosimilars. At the hearing, there was a split on how flexible the standards should be. Some testimonials proposed that the only way to be sure that a biosimilar drug is safe is through extensive clinical trials, while others argued that dangerous and expensive clinical tests are not required because they will be based on drugs that are already proven safe.

Traditional medicines have faced generic competition for decades. According to current guidelines, companies that make generic versions of traditional small-molecule drugs do not need to run their own clinical trials. They just need to demonstrate that their versions are chemically equivalent to the brand-name. Biosimilars differ from generic drugs because their active ingredients are huge biological molecules with complex structures; these molecules are often impossible to replicate in every detail—even in the hands of the original manufacturer. Small variations in production can often lead to differences in yield and function.

It could take months or even years for the FDA to hammer out its approval pathway. “It's a complex challenge. I can't put dates on our timelines for implementation,” FDA Commissioner Margaret Hamburg told a National Press Club audience in October¹.

Across the Atlantic, the European Medicines Agency (EMA) has had a framework in place since 2004 for approving biosimilars. Since that time, the EMA has approved 13 biosimilars. These include biosimilar versions of copies of erythropoietin, human growth hormone, and granulocyte colony-stimulating factor. Last month, the EMA released new guidelines on biosimilar antibodies. The EMA's draft regulation, posted on the agency's website², aims to clarify how drugmakers can copy and sell monoclonal antibodies after they lose patent protection. The document is open to public comments until May 31. According to a report by Bloomberg News, the international market for antibodies was valued at $36.4 billion in 2009 and is forecast to increase to $62.7 billion in 2015³. (sk)

http://www.reuters.com/assets/print?aid=USTRE6A04YI20101101

http://www.ema.europa.eu/ema/index.jsp?curl=pages/news_and_events/news/2010/11/news_detail_001155.jsp&murl=menus/news_and_events/news_and_events.jsp&mid=WC0b01ac058004d5c1

http://www.bloomberg.com/news/2010-11-25/novartis-teva-may-get-billion-dollar-boost-from-new-eu-rules.html?cmpid=msnmoney

FDA Approves Second Embryonic Stem Cell Clinical Trial

Advanced Cell Technology became the second company to receive FDA approval for a human embryonic stem (hES) cell clinical trial in the United States. The Marlborough, MA-based company will begin testing its retinal cell treatment this year in a dozen research subjects with Stargardt's macular dystrophy, an inherited degenerative eye disease that leads to blindness in children. Stargardt's affects an estimated 1 in 10,000 young people in the US; as the disease progresses, a layer of the retina called the retinal pigment epithelium (RPE) degenerates, causing vision loss. There is currently no treatment for Stargardt's disease.

ACT has been successful in differentiating hES cells into RPE cells. The clinical protocol will involve the injection of 50,000 to 100,000 hES-derived RPE cells into the vitreous cavity of the eye of severely affected individuals in an attempt to replace dying and no longer functioning photoreceptor cells. According to ACT, their preclinical animal studies have shown that the infusion of hES-derived RPE cells into animals improved vision and rescued the function of some diseased cells without any adverse effects.

Based on these positive preclinical results and the FDA's approval, ACT is now looking to broaden their footprint. The Company filed an Investigational New Drug (IND) Application to initiate a Phase I/II multicenter study using hES-derived RPE cells to treat patients with Dry Age-Related Macular Degeneration (Dry AMD). This disease occurs when the light-sensitive cells in the macula slowly break down, gradually blurring central vision in the affected eye; Dry AMD is found far more frequently than Stargardt's and affects more than 30 million people worldwide with nearly half of those being Americans.

Meanwhile, California-based Geron Corporation announced the enrollment of the first research subject in its Phase I clinical trial of human embryonic stem cell (hES)-derived oligodendrocyte progenitor cells for spinal cord injury (SCI). This is the first clinical stem cell trial approved by the FDA. After facing some initial difficulties, including a clinical hold by FDA, the multicenter trial has begun and is expected to end in October 2012. (sk)

ACT's Website: http://www.advancedcell.com/

Geron's Clinical Trial Website: http://clinicaltrials.gov/ct2/show/NCT01217008?term=GRNOPC1&rank=1