New Ohr Pharmaceuticals formulation of topical squalamine was found to improve anti-VEGF effectiveness for the treatment of retinal vein occlusion.
Take-home message: New Ohr Pharmaceuticals formulation of topical squalamine was found to improve anti-VEGF effectiveness for the treatment of retinal vein occlusion.
By Laird Harrison; Reviewed by John Wroblewski, MD
Hagerstown, MD-Topical squalamine as an adjuvant could significantly improve the effectiveness of anti-vascular endothelial growth factor (anti-VEGF) treatment for retinal vein occlusion, according to John Wroblewski, MD.
Squalamine inhibits platelet-derived growth factor (PDGF) and basic fibro-growth factor (BFGF) in addition to VEGF receptors 1 and 2, said Dr. Wroblewski, of Cumberland Valley Retina Consultants in Hagerstown, MD.
In a new formulation by Ohr Pharmaceuticals (OHR-102), squalamine can be administered as an eye drop that permeates the sclera into the choroid, he said.
Dr. Wroblewski described a phase II clinical trial of the combination therapy.
“Topical inhibition of these cytokines with squalamine, combined with an early PRN injection schedule, appears to preserve and enhance visual recovery in macular edema secondary to [retinal vein occlusion],” he said.
In the trial, Dr Wroblewski and a colleague recruited 20 people who had not previously been treated for their retinal vein occlusion. All had central subfield thickness (CST) of greater than 300 µm and best corrected visual acuity (BCVA) between 20/40 and 20/320.
The patients received both squalamine eye drops and intravitreous ranibizumab 0.5 mg for 10 weeks. During this time, the patients received ranibizumab every four weeks starting at week 2.
After 10 weeks, 19 of the patients were classified as “early treatment responders” who did not need a third ranibizumab injection. Eighty percent gained at least 3 lines of BCVA.
On average, the patients gained 20.3 EDTRS lines of visual acuity in these 10 weeks.
Next the researchers randomly divided the patients into two groups.
Both groups continued taking ranibizumab through week 38 as needed (PRN) depending on visual acuity and spectral domain optical coherence tomography (SD-OCT) criteria. However, 10 patients stopped getting squalamine while the other 10 continued.
At week 38, patients who had continued taking squalamine improved more in visual acuity.
On average, those who discontinued squalamine improved by an additional 3.1 letters of best-corrected visual acuity (BCVA) after the first 10 weeks. Those who continued improved by 7.4 letters.
The results compared favorably with previous trials of anti-VEGF therapy for retinal vein occlusion, Dr Wroblewski said.
In the BRAVO, CRUISE and SHORE trials, patients gained an average of 14.9 to 19.3 letters. And in these trials, patients lost 2.8-3.3 letters of BCVA 2 months after the patients received their sixth or seventh injections.
In Dr. Wroblewski’s study, the patients who discontinued squalamine lost 5.2 letters 2 months after their second injection. But those who continued lost only 0.4 letters.
Squalamine was well tolerated without ocular or systemic safety issues, he said.
The group that continued squalamine ended up with less central subfield thickness, and needed fewer injections, but the differences were slight.
The group that continued squalamine needed a mean of 1.3 fewer injections of ranibizumab between weeks 10 and 38 than the group that discontinued the drug.
“Squalamine did not prolong the time for recurrent edema,” said Dr. Wroblewski. “It did not seem to impact the injection burden. However, the daily inhibition of these cytokines did seem to reduce the degree of vision loss that accompanies recurrent macular edema.”
Dr Wroblewski acknowledged limitations in his study, as the study was very small, took place at a single site, had no control group, and was not randomized until week 10.
Still the fact that squalamine appeared to strongly affect visual acuity without a proportionate effect on macular edema or number of injections suggests to him that the study population was not particularly skewed towards people who respond well toward ranibizumab.
“A phase III multicenter, randomized study employing topical squalamine at baseline is merited,” he said.
This article was adapted from Dr. Wroblewski’s preseation at the 2015 meeting of the American Society of Retina Specialists. Dr. Wroblewski is a consultant to the company and a stockholder.