Massachusetts-based Ocular Therapeutix announced positive topline results from the SOL-1 Phase III superiority trial of Axpaxli (OTX-TKI), an investigational bioresorbable intravitreal hydrogel implant incorporating axitinib, a multi-target tyrosine kinase inhibitor, in patients with wet age-related macular degeneration.
The trial met its primary endpoint at Week 36 with 74.1% of subjects in the Axpaxli arm maintaining vision compared to 55.8% in the aflibercept (2 mg) arm (risk difference 17.5%; p=0.0006), making it the first time a novel investigational agent has demonstrated superiority over an approved anti-VEGF treatment in an FDA-aligned wet AMD trial. If the data hold through regulatory review, the axitinib implant could become the first tyrosine kinase inhibitor commercialized for retinal disease and the only wet AMD treatment carrying a superiority label — a distinction no other program in the space is currently positioned to pursue.
Trial specifics
The SOL-1 trial is a multi-center, double-masked, randomized (1:1), parallel-group Phase III study conducted at more than 100 sites in the United States and Argentina. It enrolled 344 treatment-naïve subjects with newly diagnosed wet AMD who were randomized after an eight-week loading segment in which all subjects received two aflibercept (2 mg) injections. To qualify for randomization, subjects had to demonstrate a peak treatment response — achieving approximately 20/20 vision or gaining at least 10 ETDRS letters of best corrected visual acuity (BCVA), along with central subfield thickness (CSFT) of 350 µm or less. The company described this as a population “specifically selected to lose vision,” setting a high bar for the active treatment arm. Subjects then received either a single injection of Axpaxli (0.45 mg) or a single injection of aflibercept (2 mg) and were followed monthly, with the trial remaining masked through Week 52 and continuing through Week 104.
The primary endpoint — the proportion of subjects losing fewer than 15 ETDRS letters from baseline at Week 36 — was met with a risk difference of 17.5% in favor of Axpaxli (74.1% vs. 55.8%; p=0.0006). The trial was conducted under a Special Protocol Assessment agreement with the US FDA, meaning the endpoint, statistical analysis plan, and trial design had been pre-agreed with the agency. Multiple sensitivity analyses confirmed the result.
At Week 52, a pre-specified key secondary endpoint showed the treatment effect widening: 65.9% of Axpaxli subjects maintained vision versus 44.2% in the aflibercept arm (risk difference 21.1%; p<0.0001). Rescue-free rates in the Axpaxli arm were 80.6% at Week 24, 74.7% at Week 36, and 68.8% at Week 52. Fluid control, measured by the proportion of subjects maintaining CSFT within 30 µm of baseline, favored Axpaxli at Week 36 (55.9% vs. 37.8%; nominal p=0.0013), though the difference narrowed and lost statistical significance by Week 52 (44.1% vs. 34.9%; nominal p=0.1094). As of the Week 52 database lock, no treatment-related ocular or systemic serious adverse events were observed in the Axpaxli arm, and no cases of endophthalmitis, retinal vasculitis, retinal detachment, or implant migration were reported.
Ocular Therapeutix said it intends to submit a New Drug Application based on the SOL-1 data, subject to formal discussions with the US FDA. Detailed data are scheduled for presentation at the 49th Macula Society Annual Meeting in late February 2026. Subjects have been re-dosed at Week 52 and will receive a third dose at Week 76, with masked safety follow-up continuing to Week 104. The company is also conducting a complementary Phase III non-inferiority trial, SOL-R, which randomized 631 subjects across sites in the United States, Argentina, India, and Australia, with topline data expected in Q1 2027.
Research context
Axpaxli consists of axitinib — a small molecule tyrosine kinase inhibitor that blocks vascular endothelial growth factor receptors (VEGFRs 1-3), PDGFRβ, and c-Kit — formulated within a bioresorbable hydrogel (the ELUTYX platform) designed for sustained intravitreal release. Unlike the anti-VEGF biologics that currently dominate wet AMD treatment, which neutralize circulating VEGF ligands, axitinib acts at the receptor level, inhibiting intracellular signaling downstream of multiple pro-angiogenic pathways. This pan-VEGF suppression mechanism is hypothesized to provide broader and more durable control of the abnormal blood vessel growth and vascular hyperpermeability that drive vision loss in wet AMD.
Wet AMD affects approximately 14.8 million individuals globally and 1.7 million in the United States. Current standard of care relies on repeated intravitreal injections of anti-VEGF biologics, with treatment burden remaining a persistent clinical challenge: patient discontinuation rates reach up to 40% within the first year of treatment, contributing to undertreatment and progressive vision loss. The field has evolved from monthly ranibizumab injections toward agents with extended dosing intervals, but no therapy had previously demonstrated superiority over an approved anti-VEGF in a registrational trial designed to support such a label.
The SOL-1 trial was conducted under an SPA agreement with the US FDA, however, the design is unusual in modern wet AMD development because it emphasizes prevention of moderate vision loss (categorical) and compares single-dose vs single-dose, rather than comparing to an on-label aflibercept regimen (e.g., Q8W) for the full efficacy window. As noted above, Ocular is also carrying out a second registrational study for Axpaxli, the SOL‑R study, involving repeat dosing, and assessing noninferiority versus on‑label aflibercept. The FDA has provided written agreement that the SOL-R trial design should be appropriate to support a potential NDA.
The wet AMD competitive landscape is densely populated, with several approved therapies and late-stage programs pursuing extended durability or novel mechanisms:
- Regeneron’s aflibercept 8 mg (Eylea HD), approved by the US FDA in August 2023, demonstrated non-inferiority to aflibercept 2 mg with dosing intervals extended to every 12 or 16 weeks in the PULSAR Phase 3 trial. It represents the current benchmark for reduced injection frequency among approved biologics.
- Genentech/Roche’s faricimab (Vabysmo), the first bispecific antibody targeting both VEGF-A and angiopoietin-2, was approved by the US FDA in January 2022. The TENAYA and LUCERNE Phase 3 trials showed non-inferiority to aflibercept 2 mg with up to every-16-week dosing, and the drug has seen rapid uptake.
- Australia-based Opthea’s sozinibercept (OPT-302), a soluble VEGFR-3 decoy targeting VEGF-C and VEGF-D, is in Phase 3 (ShORe and COAST trials) as an adjunctive therapy to existing anti-VEGF-A agents, aiming to achieve broader VEGF pathway suppression.
- Kodiak Sciences’ tarcocimab tedromer (KSI-301), an anti-VEGF antibody biopolymer conjugate designed for extended intravitreal half-life, remains in Phase 3 development (DAYLIGHT and GLOW trials) after mixed earlier results in the DAZZLE study.
- 4D Molecular Therapeutics’ 4D-150, an intravitreal AAV gene therapy expressing both aflibercept and an anti-VEGF-C miRNA, has entered Phase 3 (HORIZON trial) following Phase 1/2 data showing sustained anatomic improvements from a single injection.
- EyePoint Pharmaceuticals’ EYP-1901, a sustained-release intravitreal insert containing vorolanib (a TKI targeting VEGFRs), is in Phase 2 and represents the closest mechanistic parallel to Axpaxli among competing programs, though it is earlier in development.