The European Medicines Agency (EMA) published a “reflection paper” of regulatory considerations for specific gene therapy medicinal products (GTMPs) whose characteristics have been changed at various stages during clinical development, based on scientific discussions within EMA committees/working parties. Areas discussed in the nine-page paper include changes in splice donor/acceptor sequences; E4 substitutions in chimeric nonhuman adenoviral vectors; changes in selection marker in plasmid vectors; promoter exchanges in genetically modified encapsulated cells; AVV vector serotype changes; and changes in vector design, that is, redesign of retroviral (RV) vectors to RV-SIN (self-inactivating) vectors for monogenic inherited diseases. Although already established efficacy and/or safety profiles of GTMPs and their potential risk for patients should be evaluated, “the developers are strongly advised to seek product-specific scientific advice from the regulatory authorities,” the EMA concluded.

A California clinic has become the first in the state licensed to carry out a controversial chronic pain treatment that has sparked a 2-year-old FDA lawsuit. HealthLink Medical Center in Oceanside, California, is approved for the Regenexx stem cell treatment developed by Regenerative Sciences (www.regenexx.com). The company is being sued by the FDA over the use of Regenexx for chronic pain. The FDA contends that stem cell treatments constitute medication, which falls under its jurisdiction, and that Regenexx safety has not been sufficiently tested, while inspections found facilities offering the treatment do not meet its standards. Regenerative Sciences counters that because stem cells are produced by the body, they are not drugs, and thus do not need FDA approval.

StemCells (www.stemcellsinc.com) will initiate a phase I/II clinical trial of its HuCNS-SC product candidate (purified human neural stem cells) in dry age-related macular degeneration (AMD) following authorization from the FDA. The trial will evaluate safety and preliminary efficacy of HuCNS-SC cells for dry AMD. The trial will be an open-label, dose-escalation study, expected to enroll a total of 16 patients. HuCNS-SC cells will be administered by a single injection into the space beneath the retina. Patients' vision will be evaluated by conventional methods of ophthalmological assessment at predetermined intervals over a 1-year period. Patients will then be monitored for an additional 4 years in a separate observational study.

Cedars-Sinai Heart Institute researchers published clinical trial results in The Lancet, showing that treating heart attack patients with an infusion of their own heart-derived cells helps damaged hearts regrow healthy muscle. One year after receiving the stem cell treatment, scar size was reduced from 24 to 12% of the heart in the 17 patients treated with cells. Eight patients in the control group, who did not receive stem cells, saw no reduction in their heart attack scars. The clinical trial, named CADUCEUS (Cardiosphere-Derived Autologous Stem Cells to Reverse Ventricular Dysfunction), was part of a phase I investigative study of 25 patients (average age, 53 years) treated at Cedars-Sinai Heart Institute and at Johns Hopkins Hospital.

Three adults previously treated in one eye with gene therapy for Leber congenital amaurosis (LCA) received the same treatment in their other eye, resulting in further vision improvement. All three became better able to see in dim light, and two were able to navigate obstacles in low-light situations, with no adverse effects. Scientists from Children's Hospital of Philadelphia and the Perelman School of Medicine at the University of Pennsylvania led the study, published in Science Translational Medicine. The three were among 12 patients, 4 of them children, with LCA who underwent a clinical trial of the gene therapy reported in 2009. Six patients improved enough to no longer be classified as legally blind.

Celladon (www.celladon.net) completed a $43 million equity financing to advance its lead investigational product candidate MYDICAR for heart failure. Celladon plans this year to advance clinical development of MYDICAR, which was granted Fast Track Status by the FDA in December. Financing was led by new investor Pfizer Venture Investments and also included new investors Lundbeckfond Ventures, Novartis Venture Funds, H&Q Healthcare/Life Sciences Investors, and GBS Venture Partners. All previous investors participated in this round including Enterprise Partners Venture Capital, Johnson & Johnson Development Corporation, and Venrock Associates.