Amsterdam Molecular Therapeutics (www.amtbiopharma.com) has published data in the Journal of Clinical Endocrinology & Metabolism demonstrating that one-time administration of the gene therapy Glybera (alipogene tiparvovec) in five patients markedly improved chylomicron metabolism 14 weeks after consuming a low-fat meal. That improved metabolism is reflected by a much reduced level of newly formed chylomicrons in the bloodstream, considered the cause of the acute and recurring bouts of pancreatitis seen in lipoprotein lipase deficiency (LPLD) subjects. The Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) requested the additional study last year as a prerequisite for resubmission to the panel, after refusing to approve Glybera because of what it called insufficient proof of clinical benefit of Glybera as a result of low patient numbers measured for chylomicron handling for at least 12 months posttreatment. The additional data did not appear to sway the European Commission's Standing Committee of the European Parliament, which instead of approving Glybera in January instead requested additional data from the CHMP, which in turn has asked AMT for the information. In February, Amsterdam Molecular Therapeutics announced plans to be acquired by uniQure BV, in a deal—set to be completed in April—that supposes that Glybera will ultimately not be approved.
The American Society of Gene & Cell Therapy (ASGCT; www.asgct.org) has requested that the NIH Recombinant DNA Advisory Committee (RAC) no longer review protocols for gene therapy clinical trials, citing increased experience and familiarity with the field by FDA and institutional ethics and biosafety boards following more than 1000 U.S. trials over the past 20 years. “The need to review individual protocols has diminished as the research community has acquired extensive safety data and the general public has become satisfied that these protocols have not led to modification of the human genome or to creation of novel transmissible pathogenic agents,” ASGCT President R. Jude Samulski, Ph.D., and President-Elect Xandra O. Breakefield, Ph.D., wrote in a March 1 letter to Amy Patterson, M.D., director of the NIH Office of Biotechnology Activities.
During a long-term follow-up of subjects in a Phase 1 study, researchers from University of California (UC) San Francisco, UC Berkeley, and Genzyme (www.genzyme.com) gave 10 patients with moderately advanced Parkinson's disease either low or high doses of AAV2-hAADC (human aromatic L-amino acid decarboxylase) gene therapy. Results, published in the April 2012 issue of Human Gene Therapy, showed the elevated PET signal observed in the first 12 months—a significantly increased PET value compared to pre-surgery baseline—persisted over four years in both dose groups. However, the UPDRS in all patients off medication showed a marked decline in the first 12 month, followed by a slow deterioration in later years. Researchers said the data indicate stable transgene expression over four years after vector delivery and continued safety, but also show for more study, namely a controlled efficacy trial and the use of a higher vector dose.
The challenge of developing effective gene therapy treatments for PD was also reinforced by news that another such developer, Neurologix (www.neurologix.net) last month filed for protection from creditors under the US Bankruptcy Code's Chapter 7 liquidation of assets provision in US Bankruptcy Court in Wilmington, DE. Neurologix (Fort Lee, NJ)—whose pipeline includes gene therapies for depression, epilepsy, and Huntington's disease—listed debts of $12.9 million and assets of only $1.2 million. Several institutional investors comprise a majority of ownership, led by Corriente Advisors LLC with a 23% stake. The filing came a month after Neurologix hired Global Resource Partners Inc. to provide consulting and financial services after CFO Marc Panoff resigned. CEO Clark A. Johnson stepped down in September, and his successor Adrian Adams left the position two months later.
CellTex Therapeutics (www.celltexbank.com) is denying allegations submitted to the FDA by University of Minnesota Associate Professor Leigh Turner, Ph.D., that the company's operations may violate federal and Texas law. CellTex gained public attention by storing and processing stem cells injected into Texas Gov. Rick Perry by company founder Stanley Jones, M.D., a Houston orthopedic surgeon, during back surgery in July.
Turner raised questions that included the safety and efficacy of CellTex's stem cells; marketing of adult stem cells; and the amount of unregulated stem-cell therapy already involving the company. A law firm representing CellTex, Emord & Associates PC, responded with letters to the FDA and the university denying wrongdoing, accusing Turner of “numerous material and false allegations” resulting in “real and permanent harm to CellTex's reputation,” and arguing that use of university letterhead “gives apparent credence to the allegations in the complaint.”
Turner also requested that the FDA investigate South Korean-owned RNL Bio, whose technology CellTex has licensed and purchased, following news reports that patients in China and Japan died after receiving RNL Bio-prepared stem cells. A bioethicist hired by the International Cellular Medicine Society to evaluate RNL Bio's ethical and clinical practices, Glenn McGee, Ph.D., later joined CellTex as president for ethics and strategic initiatives while still listed as editor-in-chief of the American Journal of Bioethics. On February 28, two weeks after the hiring was announced, Dr. McGee announced his resignation via Twitter, adding: “I am preparing timely, lengthy, pointed comments on the whole matter.”
Researchers from the United States, Israel, and Italy have developed a gene therapy strategy that could feasibly treat both β-thalassemia and sickle cell disease, based on delivery of a lentiviral vector carrying both the human β-globin gene and an ankyrin insulator to improve gene transcription and translation, and boost levels of β-globin production. Building on the success of prior gene therapy studies in mice, and the first evaluation of gene therapy in β-thalassemia patient, the Weill Cornell Medical College (www.med.cornell.edu)-led team developed a new lentiviral vector, designated AnkT9W, which carries both the human β-globin gene and the erythroid-specific ankyrin 5′ hypersensitive (HS) barrier insulator. Stefano Rivella, Ph.D., and colleagues reported on their study in PLoS One.
