Anti-VEGF combination therapy clinically effective treatment option for nAMD patients

It is already known that nAMD is driven by VEGFs A, C, and D. This promotes angiogenesis and vascular permeability. The standard care involves Intravitreal injections of anti–VEGF-A drugs, but these do not inhibit VEGF-C and D. This may be the reason why many patients fail to respond fully.

Considering this background, researchers tested the safety and efficacy of OPT-302, a biologic inhibitor of VEGF-C and D, in combination with the anti–VEGF-A inhibitor ranibizumab in Dose-ranging, phase 2b, randomized, double-masked, sham-controlled trial enrolling nAMD patients from 109 sites across Europe, Israel, and the United States.

In this study, Participants were randomized to 6, 4-weekly, intravitreal injections of 0.5 mg OPT-302, 2.0 mg OPT-302, or sham, plus intravitreal 0.5 mg ranibizumab. The primary outcome measured in the study was mean change in ETDRS best-corrected visual acuity (BCVA) at 24 weeks.

Secondary outcomes were the proportion of participants gaining or losing ≥ 15 ETDRS BCVA letters; area under the ETDRS BCVA over a time curve; change in spectral-domain OCT (SD-OCT) central subfield thickness; and change in intraretinal fluid and subretinal fluid on SD-OCT.

The findings of the study are:

• Of 366 participants, 122, 123, and 121 were randomized to 0.5 mg OPT-302, 2.0 mg OPT-302, and sham, respectively.
• Mean visual acuity gain in the 2.0 mg OPT-302 group was superior to sham.
• There was no significant difference in the 0.5 mg OPT-302 and the sham group.
• Compared with sham, the secondary BCVA outcomes favoured the 2.0 mg OPT-302 group, with structural outcomes favouring both OPT-302 dosage groups.
• There were similarities in the occurrence of Adverse events (AEs), with 16, 7 and 10 participants in the lower-dose, higher-dose, and sham groups, respectively, developing at least one serious AE.
• In the sham group, two unrelated deaths were reported.

They mentioned, “We observed superior vision gain with OPT-302 2.0 mg combination therapy, versus standard of care, with favourable safety.

The strengths of this study include study design, generalizability of the results, participant compliance, data completeness and statistics.

Improved vision outcomes have significant impacts on a patient’s quality of life in such patients, they said.

Further reading:

https://www.aaojournal.org/article/S0161-6420(23)00066-0/fulltext