Ocular Therapeutix releases positive topline results from SOL-1

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).

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. As reported earlier,² 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 primary endpoint of SOL-1 is the proportion of patients who maintain visual acuity, a loss of <15 ETDRS letters of BCVA from baseline (day 1), at week 36. The SOL-1 primary endpoint was designed to support a potential superiority label in wet AMD based on the FDA’s 2023 draft guidance for wet AMD therapies and was agreed to by the FDA in its SPA agreement in August 2025.³

According to the company, the superiority primary endpoint at week 36 was met with high statistical significance (p=0.0006). 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.

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, according to the company. 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.

Arshad M. Khanani, MD, MA, FASRS, Director of Clinical Research at Sierra Eye Associates in Reno, Nevada, and 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.”

“To see sustained anatomic responses with 55.9% of AXPAXLI subjects maintaining CSFT within 30 microns at week 36 highlights the fluid control and stability we hope to see in everyday practice. In addition, two-thirds of subjects remain rescue-free at week 52, suggesting this could potentially be an annual treatment in many patients. These data show AXPAXLI’s potential to significantly reduce treatment burden and optimize long-term visual outcomes for our patients and, if approved, should support rapid and broad clinical adoption,” concluded Khanani.

The company also evaluated the proportion of patients maintaining CSFT within 30 μm from baseline. Results showed that at weeks 36 and 52, patients in the AXPAXLI arm demonstrated superior and sustained CSFT control as compared to subjects in the aflibercept (2 mg) arm. At week 36, 55.9% of patients treated with AXPAXLI maintained CSFT within 30 μm from baseline versus 37.8% of subjects in the aflibercept (2 mg) arm, representing a risk difference of 17.1% in favor of AXPAXLI (nominal p=0.0013). While at week 52, 44.1% of patients treated with AXPAXLI maintained CSFT within 30 μm from baseline versus 34.9% of subjects in the aflibercept (2 mg) arm, representing a risk difference of 8.4% in favor of AXPAXLI (nominal p=0.1094).

Darius M. Moshfeghi, Chief of the Retina Division at Byers Eye Institute of Stanford University School of Medicine, added, “The extended duration of disease control observed in SOL-1 would provide meaningful coverage if a patient misses a visit, which is a very real issue in clinical practice, especially in this patient population. Taken together, these data provide substantial evidence of AXPAXLI’s potential to transform how we manage wet AMD.

Patients will be re-dosed again at week 76 and will be followed on a masked basis for safety until the end of week 104. Additionally, AXPAXLI showed either statistical significance or numerical superiority to aflibercept (2 mg) in key secondary and prespecified exploratory endpoints.

In addition to SOL-1, the company is conducting SOL-R (NCT06495918), a second non-inferiority registrational trial. According to the company, the protocol rescue criteria in SOL-R of >5 ETDRS letter loss in BCVA plus a ≥75 μm increase in CSFT are designed to track more closely with real-world clinical practice as compared to the rescue criteria used in SOL-1. SOL-R is a phase 3, multi-center, double-masked, randomized (2:2:1) trial evaluating AXPAXLI dosed every 6 months versus aflibercept (2 mg) dosed every 8 weeks in treatment-naïve wet AMD patients. Patients (n=555) are enrolled across approximately 100 sites across the United States, Argentina, India, and Australia.⁴

In a prespecified exploratory analysis applying the SOL-R protocol rescue criteria to the SOL-1 results, AXPAXLI demonstrated a 77.1% rescue-free rate at week 24.

Nadia K. Waheed, MD, MPH, chief medical officer of Ocular Therapeutix, commented, “The SOL-1 data give us great confidence in the SOL-R non-inferiority study, which is being conducted in a population likely to be more stable and easier to control than SOL-1. SOL-R was intentionally designed to complement SOL-1 and further validate AXPAXLI’s durability in a six-month re-dosing paradigm.”

Ocular announced it intends to submit a New Drug Application (NDA) based on SOL-1 data, subject to planned formal discussions with the FDA. Topline data from SOL-R is expected in Q1 of 2027.

References:

1. Ocular Therapeutix™ Reports Positive Results from Landmark SOL-1 Phase 3 Superiority Trial in Wet AMD. Published February 17, 2026. Accessed February 17, 2026. https://investors.ocutx.com/news-releases/news-release-details/ocular-therapeutixtm-reports-positive-results-landmark-sol-1

2. Crago SM. Over 300 patients randomized in Ocular Therapeutix's SOL-1 phase 3 trial for OTX-TKI. Published December 4, 2024. Accessed February 17, 2026. https://www.ophthalmologytimes.com/view/over-300-patients-randomized-in-ocular-therapeutix-sol-1-phase-3-trial-for-otx-tki

3. Harp MD. Ocular Therapeutix receives FDA agreement under special protocol assessment for registrational trial of AXPAXLI. Published August 13, 2025. Accessed February 17, 2026. https://www.ophthalmologytimes.com/view/ocular-therapeutix-receives-fda-agreement-under-special-protocol-assessment-for-registrational-trial-of-axpaxli

4. Harp MD. Ocular Therapeutix reaches target enrollment of 555 patients in SOL-R trial. Published November 4, 2025. Accessed February 17, 2026. https://www.ophthalmologytimes.com/view/ocular-therapeutix-reaches-target-enrollment-of-555-patients-in-sol-r-trial