Gene-based treatment provides sustained AMD therapy

First-in-human trial explores anti-angiogenic subretinal viral vector

By Cheryl Guttman Krader;Reviewed by Andreas K. Lauer, MD
Take-home message: The first clinical trial of lentiviral gene therapy in ophthalmology met its primary objective, demonstrating safety and tolerability of subretinal administration of a lentiviral vector expressing anti-angiogenic proteins in patients with advanced exudative age-related macular degeneration.

Such findings are from the results of a dose-escalating phase I study investigating subretinal administration of a lentiviral vector expressing endostatin and angiostatin (RetinoStat, Oxford BioMedica).

In addition, assays of aqueous humor obtained through anterior chamber taps showed the treatment resulted in dose-dependent, significant, and persistent increases in expression of the endostatin and angiostatin genes.

“The phase I study of RetinoStat is the first clinical trial in ophthalmology investigating lentiviral gene therapy, and this construct offers a distinct advantage for the treatment of wet AMD as it has the potential for a much longer duration of effect than current therapies,” said Dr. Lauer, Kenneth C. Swan Professor of Ophthalmology and chief, Vitreoretinal Division, Casey Eye Institute, Oregon Health and Science University, Portland, OR.

“The phase I study is also the first time therapeutic gene expression has been directly measured in an ophthalmology clinical trial,” Dr. Lauer said. “Notably, persistence of gene expression is being maintained during long-term follow-up that so far extends beyond 4 years.”

More about the study

The phase I study enrolled 21 eyes of 21 patients ages 62 to 94 years. The treatment was administered in the operating room and involved pars plana vitrectomy followed by a single subretinal injection.

The primary objective of the study was to evaluate safety and tolerability, while biological activity was investigated as a secondary objective in these advanced patients. The study evaluated three doses of the lentiviral vector-based gene therapy. Three eyes each were treated with the lowest and medium doses, and a total of 15 eyes received the highest dose.

Assessments for safety, tolerability, and biological activity were conducted at serial visits beginning on day 1 post-injection and extending to week 48. Subjects then entered a 15-year long-term follow-up study, which is standard for gene therapy trials conducted in the United States.

In the safety review, a total of 247 adverse events have been reported to date……..


Source: Ophthalmology Times