Combined OPT-302 and Ranibizumab Delivers Significant Visual Gains

Combined OPT-302 and ranibizumab therapies can result in superior visual gains compared with ranibizumab treatment alone, according to a study published in Ophthalmology. The addition of 2.0 mg OPT-302 — a recombinant fusion protein that neutralizes the activity of VEGF-C and VEGF-D — to standard-of-care ranibizumab in participants with neovascular age-related macular degeneration (nAMD) can improve both visual acuity improvements and anatomical improvements, study authors explain.

The double-masked, randomized, controlled, phase 2b trial included 366 participants with treatment-naïve, fovea involving nAMD, with best corrected visual acuity (BCVA) between 25 and 60 early treatment diabetic retinopathy study (ETDRS) letters. Participants were recruited from 109 ophthalmology clinics across Europe, Israel, and the United States, between December 2017 and November 2018.

Participants were randomly assigned to 1 of 3 groups: combined OPT-302 and ranibizumab with 2.0 mg OPT-302, combined OPT-302 and ranibizumab with 0.5 mg OPT-302, or sham and ranibizumab. A total of 348 participants completed the study to week 24. Attrition and baseline characteristics were well-balanced across groups.

Each patient was injected every month according to their allocation. Patients in the combined OPT-302 and ranibizumab groups were treated with 2 monthly injections (50 µl of OPT-302 and 50 µl of ranibizumab). Participants in the control group were treated each month with 1 injection (50 µl of ranibizumab) and a sham injection.

The researchers found statistically superior gain in mean BCVA in those treated with 2.0 mg OPT-302 compared with the participants control group (+14.2±11.61 letters vs +10.8±11.52 letters, P =.01). No statistically significant difference was found between the mean BCVA gain of the 0.5 mg OPT-302 group and that of the control group (+9.44±11.32; P =.83).

The proportion of participants gaining more than 15 ETDRS BCVA letters was most significant in the 2.0 mg OPT-302 group, followed by the sham and 0.5 mg (45%, 40.5%, and 33.0%, respectively). The proportion of losing more than 15 letters was greatest among the 0.5 mg group, followed by the sham and 2.0 mg groups (5.4%, 3.4%, and 0.8%, respectively). No difference was found between the mean area under the curve of the groups. 

The mean decrease in optical coherence tomography (OCT) central subfield thickness (CST) was similar between the 2 combined OPT-302 and ranibizumab groups (-146.7±110.8 μm, and -147.8±113.8 μm, respectively), both of which were greater than the sham group (-133.8±97.5 μm). 

The researchers report that the proportion of participants with subretinal fluid at 24 weeks was the lowest in the 2.0 mg group, followed by the 0.5 mg, and then the sham group (18.5%, 23.2%, and 29.3%, respectively). The proportion of patients with intraretinal cysts at 24 weeks was 16.8%, 19.6%, and 21.6% in the 2.0 mg, 0.5 mg, and sham groups, respectively.

A dose-response angiographic evidence for a reduction in the choroidal neovascularization (CNV) area and reduction in total lesion area were detected in the combined OPT-302 and ranibizumab groups compared with the sham group.

Adverse events were similar across groups, with 16 (13.3%), 7 (5.6%), and 10 (8.3%) participants in the lower dose, higher dose, and sham groups developing at least 1 serious adverse event.

“We are not aware of another intravitreal treatment currently in clinical development that has shown superiority over anti-VEGF-A therapy in nAMD, which is particularly relevant to a large number of patients who experience insufficient clinical response despite regular anti-VEGF A therapy,” the study authors report. “Notwithstanding the clinical relevance of reduced dosing, and reduced cost, many patients’ key aim is to preserve or improve their vision, and a drug that has the potential to provide the best visual outcomes would have considerable clinical utility.”

The limitations of the study include a relatively short follow-up time, and that combination therapy was limited to ranibizumab (the validity of these results to combined treatment with other anti-VEGF-A drugs has to be determined). 

Disclosure: This research was supported by Opthea. One study author declared affiliations with the biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.