Ocular Therapeutix Reports Positive Phase 3 SOL-1 Trial Results for AXPAXLI in Wet AMD

Ocular Therapeutix has released positive topline results from SOL-1, its Phase 3 superiority trial of AXPAXLI for the treatment of wet age-related macular degeneration (AMD). The superiority primary endpoint at week 36 was met with high statistical significance (p=0.0006), with 74.1% of AXPAXLI patients maintaining vision compared to 55.8% for aflibercept.

SOL-1 (NCT06223958) is a multi-center, double-masked, randomized (1:1), parallel-group trial involving more than 100 clinical trial sites located in the US and Argentina. The trial completed randomization of 344 evaluable treatment-naïve subjects with a diagnosis of wet AMD in the study eye in December 2024. The primary endpoint is the proportion of patients who maintain visual acuity, defined as a loss of <15 early treatment diabetic retinopathy study (ETDRS) letters of best corrected visual acuity (BCVA), at week 36.

After an 8-week loading phase of 2 aflibercept (2 mg) injections and reaching approximately 20/20 vision or experiencing an improvement of at least 10 Early Treatment of Diabetic Retinopathy Study (ETDRS) letters of best corrected visual acuity (BCVA), patients were randomized to compare a single dose of AXPAXLI (0.45 mg) to a single dose of aflibercept (2 mg). At randomization, patients in the AXPAXLI arm (n=172) had a BCVA of 80.8 (SD of 7.6) and a Central Subfield Thickness (CSFT) of 219.3 μm (SD of 37.1). While patients in the aflibercept (2 mg) arm had a BCVA of 79.2 (SD of 7.9) and a CSFT of 226.8 μm (SD of 42.1).

The proportion of patients with <15 ETDRS letters lost from baseline at week 36 was 74.1% in the AXPAXLI arm compared to 55.8% in the aflibercept (2 mg) arm. A risk difference—the difference in the probability of maintaining vision in the treatment arm compared to the control arm as per the pre-specified statistical model—of 17.5% was observed.

The SOL-1 primary endpoint was designed to support a potential superiority label in wet AMD based on the FDA's 2023 draft guidance for wet AMD therapies and was agreed to by the FDA in its SPA agreement in August 2025.

Although the endpoint was at week 36, the trial remained masked until the week 52 durability assessment. At week 52, patients were re-dosed with their respective initial treatments of AXPAXLI or aflibercept (2 mg). The week 52 durability assessment was met with high statistical significance. The proportion of patients who maintained vision at week 52 was 65.9% in the AXPAXLI arm compared to 44.2% in the aflibercept (2 mg) arm, with a risk difference of 21.1% and a p-value of <0.0001 per the pre-specified statistical model compared to aflibercept (2 mg) patients, with an observed difference of 21.7%.

The company also evaluated the proportion of patients who did not require rescue injections as specified by the protocol rescue criteria, which includes a BCVA loss of ≥15 ETDRS letters from baseline or new vision-threatening macular hemorrhage. Rescue-free rates in the AXPAXLI arm were 80.6%, 74.7%, and 68.8% at weeks 24, 36, and 52, respectively, compared to 72.1%, 56.4%, and 47.7% for the aflibercept (2 mg) arm—showing 8.5%, 18.3%, and 21.1% in favor of the AXPAXLI arm at weeks 24, 36, and 52, respectively.

The Steering Committee Chair for the SOL Program commented on the trial results in a press release, saying, "The SOL-1 results mark one of the most important advances in the treatment of wet AMD since the advent of anti-VEGF biologics 20 years ago. AXPAXLI is the first and only drug with a novel mechanism to successfully demonstrate superiority to an approved anti-VEGF treatment in an FDA-aligned study for wet AMD."

AXPAXLI is an investigational sustained-release axitinib formulation, a tyrosine kinase inhibitor targeting VEGF pathways. The trial was conducted under FDA Special Protocol Assessment (SPA) agreement. NDA submission is planned for the United States. A confirmatory Phase 3 SOL-R trial is ongoing in the US, Argentina, India, and Australia, with topline results expected Q1 2027.

Detailed SOL-1 data will be presented at the 49th Macula Society Annual Meeting between February 25–28, 2026. Masked safety follow-up is ongoing through week 104.

Ocular Therapeutix, Inc. (NASDAQ: OCUL) is an integrated biopharmaceutical company committed to redefining the retina experience. AXPAXLI (also known as OTX-TKI) is an axitinib intravitreal hydrogel based on its ELUTYX proprietary bioresorbable hydrogel-based formulation technology. AXPAXLI is currently in Phase 3 clinical trials for wet age-related macular degeneration (wet AMD) and diabetic retinal disease, including non-proliferative diabetic retinopathy (NPDR).

Ocular's pipeline also leverages the ELUTYX technology in its commercial product DEXTENZA, an FDA-approved corticosteroid for the treatment of ocular inflammation and pain following ophthalmic surgery in adults and pediatric patients and ocular itching associated with allergic conjunctivitis in adults and pediatric patients aged two years or older, and in its investigational product candidate OTX-TIC, which is a travoprost intracameral hydrogel that has completed a Phase 2 clinical trial for the treatment of open-angle glaucoma or ocular hypertension. Ocular is currently evaluating next steps for the OTX-TIC program.