OPT-302 combined with ranibizumab: covering all the VEGF bases for superior visual gains compared with ranibizumab alone in wet AMD
A phase 2b study1 of OPT-302 (Opthea Ltd.), an anti-vascular endothelial growth factor (VEGF)-C/-D “trap” agent, in combination with ranibizumab (Lucentis, Genentech Inc.) to treat wet age-related macular degeneration (AMD) showed that administering the 2 VEGF inhibits drugs resulted in a larger improvement in visual acuity (VA) after 24 weeks compared with ranibizumab alone.
The rationale behind this treatment was to also inhibit VEGF-C and VEGF-D using OPR-302 in addition to VEGF-A, which ranibizumab, the standard of care for wet AMD, inhibits.
The randomized, double-masked, sham-controlled trial included patients with treatment-naïve neovascular AMD who were treated at 109 sites in Europe, Israel, and the US.
The patients were randomized to 6, every-4-week intravitreal injections of 0.5 mg OPT-302, 2.0 mg OPT-302, or sham plus intravitreal 0.5 mg ranibizumab. The primary outcome was the mean change in Early Treatment Diabetic Retinopathy Study best-corrected VA (BCVA) at 24 weeks. The secondary outcomes were the percentages of patients who gained or lost 15 or more letters of BCVA at 24 weeks compared with baseline and the changes in the central subfield thickness and the intra-retinal and sub-retinal fluid on spectral-domain optical coherence tomography (SD-OCT) images.
A total of 366 patients were included from December 1, 2017, to November 30, 2018. Patients were randomized to receive 0.5 mg OPT-302 (n=122), 2.0 mg OPT-302 (n=123), or sham (n=121), respectively.
The investigators reported that the 2.0-mg OPT-302 group had a significant (p=0.01) BCVA gain that was superior to sham (+14.2 ± 11.61 versus +10.8 ± 11.52 letters, respectively). The BCVA gain in the 0.5-mg OPT-302 group did not reach significance (p=0.83) compared with the sham group (+9.44 ± 11.32 letters, respectively). The structural outcomes favored both OPT-302 dosage groups. Adverse events were similar across groups, with 16 (13.3%), 7 (5.6%), and 10 (8.3%) participants in the low-dose, high-dose, and sham groups, respectively, developing at least one serious adverse event. Two unrelated deaths both occurred in the sham arm.
The investigators concluded that “significantly superior vision gain was observed with OPT-302 2.0 mg combination therapy versus the standard of care, with favorable safety.”
Opthea, according to a company press release, is currently conducting two global confirmatory phase 3 studies, ShORe (2 mg OPT-302 + 0.5 mg ranibizumab), and COAST (2 mg OPT-302 + 2 mg aflibercept [Eylea, Regeneron]). The primary endpoint for both studies is the superiority in VA gains at 12 months for the combination therapy compared with standard-of-care monotherapy.