Squalamine is a small molecule, anti-angiogenic drug with a novel intracellular mechanism of action. The drug acts against the development of aberrant neovascularization by inhibiting multiple growth factors, including vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and basic fibroblast growth factor (bFGF). Clinical evidence has shown these additional growth factors play a role in angiogenesis and ocular neovascular disease. The topical formulation of Squalamine, called OHR-102, is late stage development for the treatment of neovascular diseases of the eye and the U.S. Food and Drug Administration has awarded Fast Track Designation to the program for the potential treatment of wet AMD.
In the IMPACT study, a randomized, multi-center, masked, placebo-controlled, Phase II clinical trial completed in 2015, OHR-102 demonstrated an improvement in visual function when used in combination with an anti-VEGF agent versus anti-VEGF monotherapy. In patients with classic containing choroidal neovascularization (CNV), 42% of the patients receiving OHR-102 combination therapy achieved a ≥3 line gain at nine months, as compared to 28% in the anti-VEGF monotherapy group. A three-line gain in visual acuity is important as it represents a halving of the visual angle and would mean patients were able to see a letter half the size of what they could see at the beginning of the trial. Patients in the study also achieved a mean gain in visual acuity of +10.5 letters in the OHR-102 combination arm as compared to +5.4 letters with anti-VEGF monotherapy, a clinically meaningful benefit of +5.1 letters. Similarly, additional data from another Phase II study in retinal vein occlusion (RVO) indicated that OHR-102 combination therapy resulted in increased visual acuity compared to anti-VEGF monotherapy. In both studies, there were no safety issues identified.
OHR-102 used in combination with an anti-VEGF agent may provide several potential advantages over other combination therapy approaches currently being investigated in clinical studies including:
- Daily eye drop therapy compared to an additional intravitreal injections.
- Inhibition of multiple growth factor pathways.
- Cost advantage of manufacturing a small molecule when compared to large molecule proteins and antibodies.
Based on the data from the IMPACT study in wet AMD demonstrating a positive and clinically meaningful treatment effect of OHR-102 combination therapy, a Phase III program is being initiated