A phase 1/2A trial shows that Opthea’s novel anti-VEGF therapy, OPT-302, combined with ranibizumab may be more effective than ranibizumab alone in treating patients with wet age-related macular degeneration (AMD).
OPT-302 blocks the activity of both VEGF-C and VEGF-D, whereas ranibizumab inhibits VEGF-A. Previous results from the research team and preclinical mouse models suggest additive benefit by targeting multiple VEGF pathways concurrently.
"The results seen in Opthea's Phase 1/2A trial are very encouraging," said Pravin Dugel, MD, managing partner of Retinal Consultants of Arizona and clinical professor at the University of Southern California Eye Institute. "The study has achieved both of its objectives by demonstrating a well-tolerated safety profile and clear signals of biological activity of OPT-302. The potential to treat patients with a combination therapy to provide additional clinical benefit over the current standard-of-care, and do it with a complementary mechanism of action, would be a significant advance in the treatment of retinal neovascular disease and beneficial for our patients."
The multicenter study enrolled a total of 51 patients with wet AMD who were either treatment naïve or previously treated with intravitreal anti-VEGF-A therapy. Subjects were randomized to receive 3 intravitreal injections of OPT-302, either alone or in combination with ranibizumab at 4 week intervals, with a follow-up visit at week 12. Ranibizumab rescue therapy in the monotherapy group was provided at investigator discretion, or if there was a ≥5 letter decrease in VA and no reduction in central subfield thickness (CST) of at least 10% with presence of fluid.
Overall, OPT-302 demonstrated positive clinical activity in all patient groups. Approximately 90% of patients maintained or improved VA at week 12 compared with baseline.
Patients in the treatment-naïve group on combination therapy showed the highest visual gains, improving +10.8 letters from baseline. Anatomical benefits were also evident, with a significant reduction in mean CST and subretinal fluid.
The OPT-302 monotherapy group showed a mean gain of +5.6 letters, and less than half required rescue therapy during the study period.
OPT-302 also met its primary safety endpoint: the drug was well tolerated at all dose levels, either alone or in combination with ranibizumab.
“The potential additive benefit of OPT-302 is very promising. The novel mechanism of action of OPT-302, together with the results of this Phase 1/2A clinical trial, warrants further investigation of OPT-302 in patients with retinal neovascular diseases," said Dr. Dugel.