Lesion size plays key role in squalamine eye drops therapy

Take-Home Message: Squalamine lactate-when combined with ranibizumab for treating neovascular age-related macular degeneration-achieved improved visual function when compared with the results achieved with ranibizumab treatment alone.

Reviewed by David S. Boyer, MD

Los Angeles-A topical drug-when combined with ranibizumab (Lucentis, Genentech)-achieved improved visual function when compared with the results achieved with ranibizumab treatment alone, said David S. Boyer, MD.

Dr. Boyer highlighted the final results from the phase II Impact Study of squalamine lactate ophthalmic solution 0.2% (OHR-102, Ohr Pharmaceuticals) for treating neovascular AMD.

The size of the occult choroidal neovascularization (CNV) at baseline was what drove the vision benefits, according to Dr. Boyer, clinical professor of ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles.

Squalamine is different from the drugs that ophthalmologists are used to in that most of the anti-vascular endothelial growth factor (VEGF) drugs and the plate-derived growth factor drugs [PDGF] all have an extracellular mechanism of action, he noted.

“However, OHR-102 has multiple receptors that it can affect and has an intracellular mechanism of action,” Dr. Boyer said. “It not only affects VEGF but also PDGF and fibroblastic growth factor.”

Impact Study

Impact Study

The Impact Study included 142 patients with treatment-naïve wet AMD at 23 U.S. centers. Classic and occult CNV lesions were included in the study if they were less than 12 disc areas in size. Patients had vision ranging from 20/40 to 20/320 at baseline. Patients with diabetes who had no retinopathy were enrolled.

One hundred and twenty-eight patients completed the 9 months of the study. If patients had any retinal cystic changes, retinal or subretinal fluid, and relevant retinal pigment epithelial elevations, they were re-treated, Dr. Boyer recounted.

The primary end point of the study-i.e., a decreased number of injections in the active treatment group that received ranibizumab and OHR-102 drops compared with ranibizumab alone-was not met, he noted.

“Benefits were seen in the secondary end points: the mean gain in visual acuity and the percentage of patients with 3, 4, and 5 lines or more of vision gained,” he said.

Among the patients randomly assigned to combination therapy, they achieved 6 more letters of vision at the end of the study compared with those treated with ranibizumab monotherapy.

When looking at the patients who gained 3 lines of vision or more, this increase started early in the study, as early as 12 weeks, and continued to a 57% improvement. This increase was also apparent for patients who gained 4 or more and 5 or more lines of vision.

CNV Size

CNV size

When explaining the success of the combination therapy, Dr. Boyer pointed out that lesions described as classic CNV can be markedly different.

“Using the term 'classic' may not define the effectiveness of the drug,” he said.

An evaluation of the size of the occult lesions and the visual outcomes identified the important factor. In patients with occult CNV less than 10 mm² the patients had a 5.3-letter improvement with the combination therapy. The smallest occult lesion sizes were seen to have the best visual acuity results.

Squalamine had a good safety profile and was generally well tolerated. Two patients who received squalamine dropped out of the study because of eye swelling and pain. No serious or severe adverse effects occurred.

“The Impact Study showed robust gains in vision with the combination of OHR-102 and ranibizumab for treating classic lesions,” Dr. Boyer said. “Eighty percent of the lesions were classic with occult CNV less than 10 mm² in size. The size of the occult component was the most important factor that drove the gains in visual acuity.”

A 2-year phase III study of 650 patients is starting to evaluate treatment of patients with treatment-naive occult CNV that is less than 10 mm². Patients will be treated with ranibizumab and then randomized to the active topical drop twice daily or the vehicle.

David S. Boyer, MD

E: vitdoc@aol.com

This article was adapted from Dr. Boyer’s presentation at the 2015 meeting of the American Academy of Ophthalmology meeting. Dr. Boyer is a consultant for Ohr Pharmaceuticals.