Ohr Pharmaceuticals' MAKO study utilizing Squalamine and Lucentis does not meet primary endpoint

(c) AAO

Ohr Pharmaceutical, Inc. has reported topline data from the MAKO study that did not meet its primary efficacy endpoint. The study evaluated efficacy and safety of topically administered squalamine in combination with monthly Lucentis® injections for the treatment of wet age-related macular degeneration. The primary efficacy endpoint was the mean visual acuity gain at nine months, using a mixed-effects model for repeated measures (MMRM) analysis.

Squalamine was initially discovered on the basis of its anti-bacterial activity. It has proven to be a broad spectrum antimicrobial compound that exhibits potent activity in vitro and in vivo against gram negative and gram positive bacteria, fungi, protozoa, and many viruses. Subsequent studies in vitro and in animals demonstrated various unanticipated pharmacological properties. In several vertebrate models, squalamine exhibits systemic anti-angiogenic activity against rapidly proliferating blood vessels that arise in pathological settings. As a consequence, it is being evaluated in several human clinical trials for cancer and fibrodysplasia ossificans progressiva, as well as in retinal indications such as macular degeneration and diabetic retinopathy. Ohr Pharmaceuticals was evaluating squalamine in a Phase III study applied topically to the eye.

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Please read the disclaimer here.

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Ohr Pharmaceuticals' MAKO study was a multi-center, 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:
1. topical squalamine lactate ophthalmic solution, 0.2% twice daily and monthly Lucentis® injections (combination arm) (n=119)
2. topical placebo twice a day and monthly Lucentis® injections (monotherapy arm) (n=118)

Eligibility criteria for the study eye included: 

- newly diagnosed with wet-AMD and no previous treatment, 

- occult neovascularization, if present, measured less than 10mm² as assessed by fluorescein angiography
- visual acuity between 20/40 and 20/320 on ETDRS.

A total of 237 subjects were randomized. Subjects receiving squalamine combination therapy (n=119) achieved a mean gain of 8.33 letters from baseline versus 10.58 letters from baseline with Lucentis® monotherapy (n=118). There were no differences in the safety profile between the two treatment groups.

Earlier, a Phase-2 trial that looked at safety and efficacy of Squalamine Eye Drops in combination with Lucentis injections. The study sought to determine if squalamine was safe, and whether Squalamine Eye Drops could reduce the number and frequency of Lucentis injections required to control wet AMD.

The Phase-2 study results showed that the eye drops were safe enough, but treatment failed to decrease the average number of Lucentis injections required by the study participants. 31% of the study participants who received the combined Lucentis/squalamine treatment gained 3 or more letters on ETDRS, while 25% of participants who received Lucentis treatment alone.

Though the treatment did not reduce the need for, or the frequency of, eye injections, the drug demonstrated positive changes in visual acuity – both in the combination group, as well as in subjects with a specific type of AMD lesion. 37 participants with classic AMD lesion who received the combination of Lucentis and squalamine treatment gained 11 letters on the ETDRS Eye Chart, while the monotherapy arm (Lucentis alone) demonstrated 5 letters of improvement with Lucentis treatment alone. Classic AMD lesions have also shown benefit in other studies of combined treatment.

Based on this outcome, the Phase-3 trial was started.

What will happen to Ohr Pharmaceuticals now?

It is difficult to say. Both Phase-2 and Phase-3 clinical trials have been a disappointment in their outcomes, which could mean an end to Squalamine eye drops, unless the company has something up its sleeve. They do mention the SKS sustained release technology, but will investors have the stomach to experiment with it is a big question.

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Sources: Ohr Pharmaceuticals; Wikipedia; ClinicalTrials;