In a milestone for exudative retinal disease therapy, Ocular Therapeutix announced today that its investigational agent Axpaxli (OTX-TKI) outperformed an FDA-approved anti-VEGF 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 to the US Food and Drug Administration on an accelerated pathway.

“The data overwhelmingly show we have a drug that has the potential to fundamentally change what is possible in wet AMD treatment,” said Pravin U. Dugel, MD, executive chairman, president, and CEO of Ocular Therapeutix, as he presented the SOL-1 top-line data during a conference call. “Axpaxli did not just perform well, but it is now the first and only investigational product in wet AMD with a novel mechanism of action to successfully demonstrate superiority to an approved anti-VEGF agent since their initial approval in wet AMD more than 20 years ago. Many programs have tried to reach this bar. All have failed. Today, Axpaxli succeeded.”

SOL Trial Data

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.

Axpaxli demonstrated superior anatomic outcomes as well, 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).

“In practice, retina specialists … make decisions based on earlier functional changes and anatomic control based on fluid on optical coherence tomography (OCT) imaging,” observed Arshad M. Khanani, MD, MA, FASRS, director of clinical research at Sierra Eye Associates and steering committee chair for the SOL clinical program, during the conference call. “We tend to prioritize anatomic control, first and foremost, because it is typically the earliest indicator of disease progression and future vision loss. This is where the SOL-1 data become extremely compelling. We saw sustained and tighter fluid control with Axpaxli through the week 36 primary endpoint…. This level of sustained anatomic stability reflects a degree of predictable and durable disease control that extends far beyond what we typically achieve with available therapies today.”

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.

“Safety is king, and there were no safety concerns in this study,” commented Darius M. Moshfeghi, chief of the Retina Division at Stanford University’s Byers Eye Institute, during the conference call. “If approved, Axpaxli is very well positioned for rapid adoption. This agent delivers exactly what the data-driven retina community is looking for to alter their practice patterns: good safety, durable visual gain maintenance and fluid control, predictable dosing, and a seamless integration into clinic workflow. From a clinician’s perspective, this is the kind of data set that gives you confidence to rapidly integrate Axpaxli, if approved, into your wet AMD treatment regimen.”

Future Axpaxli Direction

The SOL-1 trial was conducted under a special protocol assessment agreement with the FDA to support a potential superiority label. “Looking ahead, we believe the strength and statistical integrity of SOL-1 data provide a clear path toward regulatory submission,” said Dr. Dugel. “Consistent with recent FDA commentary, we believe SOL-1 represents exactly the type of single well-controlled FDA-aligned registrational trial that can support an NDA filing. Accordingly, we plan to hold formal discussions with the FDA and pursue approval through the accelerated 505B2 pathway thereafter.”

This possible accelerated NDA strategy will not affect the company’s 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. “SOL-R remains an important component of our global regulatory and commercial strategy, and today’s SOL-1 results only strengthen our confidence in its outcome,” said Dr. Dugel. 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 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 nonproliferative 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. RP