Ocular Therapeutix's Axpaxli Demonstrates Superiority Over Aflibercept in Wet AMD Phase 3 Trial

Ocular Therapeutix reported that its investigational drug Axpaxli demonstrated superior vision maintenance compared to aflibercept in patients with wet age-related macular degeneration in the SOL-1 Phase 3 superiority trial. The company plans to meet with the FDA to discuss plans for a regulatory submission based on the results.

The SOL-1 trial evaluated a single dose of Ocular's drug compared to a single dose of aflibercept following an eight-week loading portion of the study in which all 344 newly diagnosed wet AMD study participants received two injections of aflibercept. Results show that at week 36, 74.1% of patients in the Axpaxli arm maintained vision compared to 55.8% of participants in the aflibercept group, a 17.5% risk difference (p=0.0006), meeting the trial's superiority primary endpoint with high statistical significance.

The study remained masked to assess durability of the therapy. At week 52, 65.9% of patients in the Axpaxli arm maintained vision compared to 44.2% of those in the comparator group, a 21.1% risk difference (p<0.0001). Rescue-free rates in the Axpaxli arm were 80.6%, 74.7%, and 68.8% at weeks 24, 36, and 52.

In addition to achieving the primary endpoint, Axpaxli showed either statistical significance or numerical superiority to aflibercept in key secondary and prespecified exploratory endpoints. 55.9% of subjects treated with Axpaxli maintained central subfield thickness within 30 μm from baseline at week 36, a 17.1% risk difference (nominal p=0.0013) compared to aflibercept subjects. 77.1% of Axpaxli subjects randomized in SOL-1 would have been rescue-free at week 24 using SOL-R rescue criteria which align closely with clinical practice.

To date, the study drug has been generally well tolerated with no treatment-related ocular serious adverse events reported. At the 52-week mark, participants were re-dosed with the treatments that they initially received and will be re-dosed again at week 76. Masking will continue and the study will follow patients through week 104. The company plans to present more detailed results from the study during the Macula Society Annual Meeting in San Diego.

The trial was conducted under a Special Protocol Assessment agreement with the FDA. Ocular plans to submit a New Drug Application based on SOL-1 data, subject to planned formal discussions with the FDA. A second Phase 3 test of Axpaxli is expected to yield preliminary data in the first quarter of next year.

Axpaxli's main pharmaceutical ingredient is axitinib, a small molecule tyrosine kinase inhibitor intended to stop abnormal blood vessel growth underneath the retina that leaks fluid and affects the macula. The drug employs a bioresorbable hydrogel technology that can time the release of a drug anywhere from days to months. Ocular is aiming for a dosing interval of six months or longer.

The trial marks the first successful demonstration of superiority in an FDA-aligned wet AMD trial comparing a novel investigative agent to an approved anti-VEGF treatment. In the wet form of age-related macular degeneration, abnormal blood vessel growth underneath the retina leaks fluid that affects the macula, the central part of the retina.

Despite the study meeting its goals, Ocular's stock price opened Tuesday at $6.41, down more than 27% from Friday's closing price. The stock traded at $6.86, down $2.03 or 22.80%, after closing Monday at $8.88. The stock has traded between $5.78 and $16.44 in the past 52-week period.