In a milestone for exudative retinal disease therapy, Ocular Therapeutix announced that its investigational agent Axpaxli (OTX-TKI) outperformed an FDA-approved anti-VEGF drug in the phase 3 SOL-1 trial for neovascular (“wet”) age-related macular degeneration (nAMD). The company said data from SOL-1 will support a new drug application (NDA) to the US Food and Drug Administration (FDA) on an accelerated pathway.

Axpaxli is a bioresorbable intravitreal hydrogel incorporating axitinib, a tyrosine kinase inhibitor (TKI) with antiangiogenic activity. The multicenter SOL-1 trial enrolled 344 treatment-naïve patients, comparing a single intravitreal injection of Axpaxli with aflibercept 2 mg (Eylea; Regeneron), the standard of care, following an 8-week loading regimen. The trial met its primary endpoint at week 36, with 74.1% of Axpaxli-treated subjects maintaining visual acuity—defined as loss of fewer than 15 ETDRS letters—compared with 55.8% in the aflibercept arm, representing a 17.5% risk difference (P=.0006). At week 52, 65.9% of subjects maintained vision on Axpaxli vs 44.2% on aflibercept, a 21.1% risk difference (P<.0001). Rescue-free rates were also higher in the Axpaxli group, at 80.6%, 74.7%, and 68.8% at weeks 24, 36, and 52, respectively, vs 72.1%, 56.4%, and 47.7% for aflibercept.

In addition, Axpaxli demonstrated superior anatomic outcomes, the company reported. At week 36, 55.9% of treated patients maintained central subfield thickness (CST) within 30 μm of baseline, compared with 37.8% for aflibercept (risk difference 17.1%, nominal P=.0013). Week 52 CST control remained numerically superior at 44.1% vs 34.9%, although this did not reach nominal statistical significance (P=.1094).

According to Ocular Therapeutix, safety data were consistent with previous studies. Axpaxli was generally well tolerated, with no treatment-related ocular serious adverse events, including endophthalmitis, retinal vasculitis, or implant migration. Subjects were re-dosed at week 52, and the trial will continue masked through week 104 to assess long-term safety and durability.

The SOL-1 trial was conducted under a special protocol assessment agreement with the FDA to support a potential superiority label. Ocular Therapeutix said this possible accelerated NDA strategy will not affect its ongoing global SOL-R noninferiority trial. That trial has enrolled more than 550 patients, and top-line data are expected in the first half of 2027. Patients who complete either SOL-1 or SOL-R will be eligible for the SOL-X open-label extension, which will assess long-term outcomes and the effects of delayed initiation of Axpaxli.

Ocular Therapeutix said it will present more detailed results from SOL-1 at the Macula Society’s annual meeting in San Diego later this month. The company is also preparing to begin the HELIOS phase 3 program for non-proliferative diabetic retinopathy. The study will employ an ordinal diabetic retinopathy severity score endpoint, agreed to with the FDA through a special protocol assessment for HELIOS-2, and will evaluate dosing intervals of 6 and 12 months.