OPT-302 2.0 mg plus ranibizumab leads to superior vision gains in nAMD

Treatment with 2.0-mg OPT-302, a biologic inhibitor of vascular endothelial growth factor (VEGF)-C and D, in combination with ranibizumab, an anti‒VEGF-A inhibitor, results in greater vision gains when compared with the current standard of care for neovascular age-related macular degeneration (nAMD), reports a study. In addition, the combined therapy has an acceptable safety profile.

“Significantly superior vision gain was observed with OPT-302 2.0 mg combination therapy, versus standard of care, with favourable safety,” the researchers said.

A total of 366 participants with treatment-naïve nAMD were enrolled in this phase IIb, randomized, double-masked, sham-controlled trial from 109 sites across Europe, Israel, and the US. They were randomly assigned to six, four-weekly, intravitreal injections of 0.5-mg OPT-302, 2.0 mg OPT-302, or sham, plus intravitreal 0.5-mg ranibizumab.

Mean change in Early Treatment Diabetic Retinopathy Study (ETDRS) best-corrected visual acuity (BCVA) at 24 weeks was the primary outcome. Secondary ones included the proportion of participants gaining or losing ≥15 ETDRS BCVA letters, area under the ETDRS BCVA over time curve, change in spectral-domain optical coherence tomography (SD-OCT) central subfield thickness, and change in intraretinal fluid and subretinal fluid on SD-OCT.

Of the participants, 122 were randomized to 0.5-mg OPT-302, 123 to 2.0-mg OPT-302, and 121 to sham treatment. Mean visual acuity gain with 2.0-mg OPT-302 was significantly superior to sham (14.2 vs 10.8 letters; p=0.01), while the 0.5-mg OPT-302 showed no significant difference from sham (9.44 letters; p-0.83). [Ophthalmology 2023;130:588-597]

“The mean gain in visual acuity was 14.22 letters in the 2.0-mg OPT-302 group compared with 10.84 letters in sham,” the researchers said. “This 3.4-letter difference is driven by a range of responses, including many patients with substantially higher vision gains.”

Likewise, the 2.0-mg OPT-302 group showed better secondary outcomes compared with those in the sham group, with structural outcomes favouring both OPT-302 dosage groups.

“Vision gains in the higher dose OPT-302 group were supported by anatomic improvements in both OPT-302 treatment groups compared with sham,” the researchers said. Although central subfield thickness (CST) was almost normalized in all treatment groups, making it difficult to detect a difference, a greater reduction in CST was observed in the OPT-302 treatment groups, with better retinal drying.”

Chance finding

The reason why the anatomic improvements in the lower-dose OPT-302 group did not result in superior vision gains relative to sham remains unclear. The researchers suggest a chance finding. However, “changes do sometimes precede vision gain, and it is possible that a difference may emerge with time.”

Another possibility is that the slight differences in baseline characteristics between the lower-dose group and the sham group reduced the relative vision benefits of the former.

“However, consistent with the randomized design, the groups were generally well matched, and these differences are small, such that they might not be expected to produce a large biological effect,” the researchers said. “It is possible that OCT is more sensitive at detecting a benefit than BCVA, which varies considerably within and between individuals, making it harder to detect a difference.”

“A positive dose response supports the hypothesis that OPT-302 is producing a biological response, but the impact of treatment on vision needs to be further elucidated in future trials,” they noted.

Additionally, adverse events (AEs) did not significantly differ across groups. At least one AE occurred in 16 (13.3 percent), seven (5.6 percent), and 10 (8.3 percent) participants in the lower-dose, higher-dose, and sham groups, respectively. Two unrelated deaths, however, occurred in the sham group.