Squalamine Eye Drop Fails in Wet AMD

No benefit seen when combined with Lucentis.

After an odyssey of more than 20 years of clinical trials for various diseases (including lung cancer and foot ulcers), with studies undertaken by 3 different companies, the aminosterol antiangiogenic squalamine, synthesized from the liver of the dogfish shark, may have run out of chances for commercialization.

The latest effort, the phase 3, 237-patient MAKO trial for wet AMD conducted by Ohr Pharmaceuticals, failed to add any benefit when a squalamine eyedrop was used in combination with monthly Lucentis (Genentech). In fact, at 9 months, patients on Lucentis monotherapy achieved a mean gain of 10.58 letters compared to a mean gain of 8.33 letters in the combination group. These results were despite the fact that Ohr had used its phase 2 IMPACT trial to select the patient types most likely to benefit from its therapy.

The IMPACT trial raised hopes that squalamine could be effective in achieving additional visual gains when used as a topical supplement to anti-VEGF injections. Patients in the phase 2 study with classic disease achieved a mean vision gain of 6 additional letters when using squalamine in combination with Lucentis.

“We are very disappointed with the outcome of the MAKO study,” commented Jason Slakter, MD, CEO of Ohr, in a news release. “We are grateful to the patients and physicians who participated in the clinical trial. Based on these results, we intend to evaluate strategic alternatives to maximize shareholder value.”

The MAKO study was a multicenter, randomized, double-masked, placebo-controlled clinical trial to evaluate the efficacy and safety of squalamine combination therapy for the treatment of wet AMD. Subjects were randomized 1:1 to receive topical squalamine lactate ophthalmic solution, 0.2%, twice daily and monthly Lucentis injections or topical placebo twice daily and monthly Lucentis injections.

Eligibility criteria for the study eye included new diagnosis with wet AMD and no previous treatment, occult neovascularization, if present, measuring less than 10mm2 as assessed by fluorescein angiography, and visual acuity between 20/40 and 20/320. A total of 237 subjects were randomized. Visual acuity was measured monthly using the Early Treatment of Diabetic Retinopathy Study (ETDRS) eye chart. The primary efficacy endpoint was the mean visual acuity gain at 9 months, using a mixed-effects model for repeated measures (MMRM) analysis.

Squalamine was originally developed by Magainin Pharmaceuticals in the mid 1990s based on the work of researcher Michael Zasloff, but failed in several indications. It was later tried in wet AMD by Genaera Corp., which sold the rights to Ohr in 2009.