Intravitreal siRNA PF-04523655 stabilized vision in patients with neovascular AMD

Fort Lauderdale, FL-Intravitreal small-interfering RNA (siRNA) PF-04523655 (Quark; licensed to Pfizer) used to treat choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) seems to be safe and well tolerated in an interim phase I analysis. No adverse events were observed up to the 3,000-µg dose, said Quan Dong Nguyen, MD, MSc, assistant professor of ophthalmology, retina division, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore. He reported the results for the siRNA PF-04523655 AMD Investigation.

PF-04523655 has been show to cause regression of CNV in experimental studies of mice and primates.

Stratum 1 of this study was an open-label dose-escalating trial of nine doses of PF-04523655 ranging from 50 to 3,000 µg in 27 patients with advanced neovascular AMD to assess safety. In stratum 2 of the study, four doses (1, 1.5, 2.25, and 3 mg) were tested. Patients received one intravitreal injection of the compound on day 0. They were followed to day 28 for safety and bioactivity and then for 2 years to assess the safety of the drug. Patients could receive rescue therapy with ranibizumab (Lucentis, Genentech) if the compound was ineffective.

“After the one injection, the drug was safe and tolerable for patients with AMD and most adverse events were mild and thought to be related to the injection procedure,” Dr. Nguyen said. “There were no drug-related adverse events for all doses of the compound. Evidence of bioactivity was detected. Stable vision was achieved in nearly 90% of the patients as well as a gain of three lines of vision in about 11% of patients.”

Further investigations are planned to investigate bioactivity after repeated administrations of the compound.