Topical squalamine shows encouraging results in phase 2 studies

Issue: August 10, 2015

VIENNA — Final results of the phase 2 IMPACT study of topical squalamine lactate in the treatment of neovascular AMD showed a trend toward increased efficacy in specific lesion types, according to a speaker.

Perspective from Timothy G. Murray, MD

Squalamine is a small molecule that counteracts multiple growth factors implicated in the angiogenic process, including VEGF and PDGF, Jeffrey Heier, MD, said at the American Society of Retina Specialists meeting. The IMPACT study evaluated the effects of OHR-102 (0.2% squalamine lactate ophthalmic solution, Ohr Pharmaceutical) in combination with anti-VEGF in treatment-naïve patients with wet age-related macular degeneration (AMD) and vision between 20/40 and 20/320. Patients recruited across 23 U.S. sites received Lucentis (ranibizumab, Genentech) injection at day zero and then were randomized 1-to-1 to squalamine topical therapy or placebo eye drops administered twice daily. Patients were followed monthly and re-treated with ranibizumab as needed based on strict OCT-guided criteria. The number of re-treatments were similar between the two groups.

Jeffrey Heier, MD

“Outcomes were similar with respect to mean change in vision and three-line gainers, although there was a trend toward better outcomes in the squalamine group,” Heier said, adding that, in both the classic containing lesions and the smaller occult lesions less than 4 disc areas, there was a benefit in mean change in vision and three-line gainers in the squalamine-treated group.

The topical therapy was generally well tolerated, he said. A phase 3 development program in a targeted population based on complete analysis of the IMPACT study results is under design.

In a separate presentation, John Wroblewski, MD, also reported “positive results” at week 38 of an investigator-sponsored phase 2 study of OHR-102 for treatment of macular edema secondary to retinal vein occlusion, according to a press release from Ohr Pharmaceutical.

The extension study followed 20 subjects who were randomized to either continue or discontinue squalamine drop therapy after initially undergoing a combined treatment with squalamine and ranibizumab in the first 10 weeks. Ranibizumab was administered monthly as needed based on OCT findings.

According to the press release, from week 10 to 38, patients in the combined treatment group vs. ranibizumab alone treatment group gained a mean of 7.4 letters in visual acuity vs. 3.1 letters. Between weeks 10 and 38, a mean of two ranibizumab injections were needed in the combined treatment group vs. 3.3 injections in the ranibizumab only group. — by Michela Cimberle

Disclosure: Heier reports he is a consultant to Alcon, Allergan, Avalanche, Bayer, ForSight Vision, Genentech, Ohr Pharmaceutical, Regeneron, RestorGenex and Xcovery.

Perspective

Timothy G. Murray, MD

Jeffrey Heier, MD, presented the phase 2 study results for topical squalamine in neovascular AMD. The primary take home point from the phase 2 study is that topical squalamine is well-tolerated and exhibited no significant safety concerns. The clinical implications for the use of topical squalamine remain unclear as the need for re-treatment with intravitreal anti-VEGF was essentially unchanged with, or without, the use of topical squalamine. Heier noted a potential for improvement in visual acuity outcomes when combined topical squalamine/anti-VEGF was used in small, predominantly classic neovascular AMD. Heier noted that this result was not statistically significant and cautioned that phase 3 clinical trial data would be required to address the role of topical squalamine. The retina community remains entranced by the possibility of a viable topical therapy for neovascular AMD.

Timothy G. Murray, MD

Bascom Palmer Eye Institute

Miami

Disclosures: Murray reports no relevant financial disclosures.