Ocular Therapeutix, Inc. has received the FDA’s agreement for a Special Protocol Assessment (SPA) of the planned design for a registrational trial evaluating AXPAXLI (OTX-TKI) for the treatment of non-proliferative diabetic retinopathy (NPDR).
Take it from the top: What does SPA mean, exactly?
An SPA is a process where companies request a meeting with the FDA to come to an agreement on the design or size specifications of certain clinical trials for a specific investigational candidate in development.
The timeframe: An SPA request should be submitted (at minimum) 90 days prior to the initiation of a study, after which the FDA will conduct a 45-day review (though it’s not uncommon for the review to extend beyond 45 days).
And the intent for this?
For the FDA to “determine if [the company, in its trial design] adequately address[es] scientific and regulatory requirements for a study that could support market approval” of that investigational asset.
But keep in mind: An SPA agreement doesn’t necessarily guarantee the FDA will accept the filing of a new drug application (NDA) or biologics license application (BLA)—though it ideally improves those applications’ quality—or that the respective trial results will support regulatory approval.
Duly noted. Now to our topic of discussion … talk about AXPAXLI.
What it is: An investigational, bioresorbable hydrogel intravitreal (IVT) implant—with anti-angiogenic properties—designed to continuously deliver axitinib (an FDA-approved small-molecule, multi-target tyrosine kinase inhibitor [TKI]) for the following proposed indications:
- NPDR
- Diabetic macular edema (DME)
- Wet age-related macular degeneration (AMD)
- Other vascular endothelial growth factor (VEGF)-mediated retinal diseases
Its delivery mode: Administered via a 25G needle with a 9-to-12-month target release through the company’s proprietary and patented ELUTYX technology platform.
Give me a rundown on that platform.
ELUTYX is a bioresorbable polymer matrix hydrogel developed to provide localized sustained-release drug delivery (such as AXPAXLI).
- The platform is also biocompatible and reportedly tunable for use in various locations within the eye (based on a number of supporting clinical studies)
The intent: To maximize therapeutic efficacy while minimizing systemic exposure, according to Ocular Therapeutics.
Noted. So in the context of this SPA, what do we know about its trial?
At this time, no further details have been shared—aside from an expected NPDR indication.
- Executive Chairman, President, and CEO Pravin U. Dugel, MD, noted the SPA agreement as a “major milestone” that “ensures direct FDA alignment with our proposed approach for NPDR” and a clear regulatory path for AXPAXLI.
As for when more information may be shared: Ocular Therapeutix stated it will release more details on its clinical strategy for AXPAXLI’s NPDR and DME indications during the company’s Investor Day on Sept. 30.
In the meantime, how has AXPAXLI performed in other clinical evaluations?
Sticking with NPDR, the company reported positive 48-week data in June 2024 from the phase 1 HELIOS trial.
The crux of that data:
- AXPAXLI was found to be well-tolerated
- AXPAXLI-treated patients demonstrated improvements (versus sham-treated patients) in central subfield thickness (CST) ≥2-step Diabetic Retinopathy Severity Scale (DRSS)
And more recently: Just a few weeks ago, investigators reported promising new results on macular volumetric fluid outcomes and a longitudinal quantitative ultra-widefield (UW) retina leakage assessment.
And for its wet AMD indication?
Its regulatory pathway journey is even further along, as the candidate is currently under evaluation in the phase 3 SOL-1 (NCT06223958) and SOL-R studies (NCT06495918).
For the future: Topline data is expected by Q1 2026 (for SOL-1) and the first half (H1) of 2027 (for SOL-R.
- The expectation: The SOL program could enable dosing every 6 months to as infrequently as every 12 months.
A look back at our coverage on this: Check out the 12-month topline data reported in 2023 from a phase 1 study on AXPAXLI for wet AMD.
Lastly, what’s the regulatory pathway plan for AXPAXLI?
In its Q2 2025 report, Ocular Theraputix shared plans for a potential NDA filing (for a wet AMD indication) with the FDA following the release of topline data from the SOL-R study (which, keep in mind, won’t be until 2027).
As of now: The company intends to include both phase 3 SOL studies in its filing as “adequate and well-controlled studies” to support its potential NDA submission and product label for wet AMD.
- See here for plans to incorporate a single long-term extension study for both SOL trials.
The potential: If approved, Ocular Therapeutix noted that AXPAXLI could become the first product for wet AMD “with a superiority label based on the SOL-1 trial” with redosing as infrequently (potentially) as every 12 months.