Gene Therapy Briefs

Advanced Cell Technology (ACT; www.advancedcell.com) said its ability to carry out the first human embryonic stem cell (hESC) trial in Europe won't be affected by the Court of Justice of the European Union's decision that stem cell research based on the destruction of human embryos cannot be patented (see Legal Affairs on page 8 for more information about this decision).

“It should have minimal impact on our commercial efforts in the EU,” Gary Rabin, ACT's chairman and CEO, said, because ACT's European programs employ a single-cell blastomere technique that allows for deriving hESC lines without destroying embryos. ACT has begun treating patients as part of a phase I/II clinical trial for Stargardt's macular dystrophy using retinal pigment epithelium derived from hESCs.

Amsterdam Molecular Therapeutics (AMT; www.amtbiopharma.com) laid off half its workforce, down to 45 employees, and suspended its development of Glybera for lipoprotein lipase deficiency, and its Duchenne muscular dystrophy program. The moves followed rejection of a marketing authorization for Glybera by the European Medicines Agency's (EMA) Committee for Medicinal Products for Human Use (CHMP). Glybera's benefits did not outweigh its risks despite the drug's potential value, the CHMP concluded.

“In our industry, the difference between success and failure is often tiny. And in this particular case I would say it was just one voice in the CHMP,” AMT CEO Jörn Aldag told analysts. The CHMP prevailed over EMA's Committee for Advanced Therapies, which said Glybera was approvable subject to postmarketing studies.

Oxford BioMedica (www.oxfordbiomedica.co.uk) and the Mayo Clinic (Rochester, MN) have teamed up for an R&D collaboration that aims to develop a gene therapy for treating chronic glaucoma. The partners will carry out preclinical work to test the feasibility of using a therapeutic based on Oxford BioMedica's LentiVector gene delivery system expressing a COX-2 gene and a PGF-2α receptor gene, for use in reducing intraocular pressure.

Oxford BioMedica has an option to exclusively license Mayo Clinic's glaucoma technology in the United States, on completion of preclinical studies. Oxford BioMedica said its LentiVector technology can stably deliver genes into cells with up to 100% efficiency, and can integrate genes into nondividing cells such as neurons and retinal cells.

Sanofi (www.sanofi.us), which completed a $20.1 billion acquisition of Genzyme in April, will restructure R&D operations by consolidating into a single new Genzyme R&D Center the old Genzyme's rare disease program, and the multiple sclerosis programs of both predecessor companies. Sanofi will absorb the global operations of Genzyme's former biosurgery, oncology, and renal divisions.

The restructuring will be led by David Meeker, M.D., Genzyme's operating chief, whom Sanofi promoted to CEO of the new Genzyme unit effective November 1. Dr. Meeker joined Genzyme in 1994 as medical director to work on the cystic fibrosis gene therapy program. The new Genzyme unit is seeking additional space in the Boston/Cambridge market.

In a trial led by Oxford University in collaboration with Imperial College London, a 63-year-old arbitration lawyer from Bristol, U.K., is the first patient to be treated by a gene therapy technique for an incurable form of blindness. The technique is designed to save his sight by reversing his choroideremia, a rare genetic blindness.

Jonathan Wyatt is the first of 12 patients to be treated by the gene therapy in one eye. The other eye will act as a control, but will also be treated if the therapy proves successful over the next 2 years. The trial's leader, Prof. Robert MacLaren of the University of Oxford, said if the gene therapy works, it could be used to treat several eye disorders, including macular degeneration.

Geron (www.geron.com) presented phase I data showing that GRNOPC1 “has been well tolerated with no serious adverse events” after the lowest intended dose of the human embryonic stem cell-based therapy was given to four patients with complete thoracic spinal cord injuries.

GRNOPC1 was administered between 7 and 14 days after injury. Low-dose tacrolimus was given for temporary immunosuppression from time of injection for 46 days, when the dose was tapered and withdrawn completely at 60 days. A few mild adverse events related to tacrolimus were reported, but with no evidence of cavitation in the spinal cord at the injury sites on MRI, no unexpected neurological changes, and no evidence of immune responses to GRNOPC1.

Jennerex (www.jennerex.com/) published clinical trial data in Nature showing that its lead product candidate, the oncolytic virus JX-594, reproducibly infected, replicated in, and expressed transgene products within cancer tissue after intravenous infusion. Normal tissues were not significantly affected clinically.

David Kirn, M.D., Jennerex president and CEO, said that the platform technology opens up the possibility of selectively expressing multiple transgene products with complementary mechanisms of action at high concentration in tumors systemically. He also disclosed plans to initiate a global, randomized, controlled phase IIb trial of JX-594 in patients with hepatocellular carcinoma having failed sorafenib (Nexavar) treatment.

Fresenius Medical Care (FMC; www.fmcna.com) was granted orphan designation (EU/3/11/904) by the European Commission for heterologous human adult liver-derived stem cells for ornithine transcarbamylase deficiency—one of the urea cycle disorders, and a nervous system disorder affecting fewer than 5000 people across the European Union.

FMC said the stem cells, when implanted in a patient, will develop into mature, healthy liver cells that can produce the ornithine transcarbamylase enzyme, restoring the normal urea cycle and relieving symptoms of the disease. Clinical trials of the stem cells in patients have yet to be launched.