Ocular Therapeutix, Inc. recently announced additional positive Week 52 data from the SOL-1 phase 3 superiority trial of AXPAXLI (OTX-TKI) for the treatment of wet age-related macular degeneration (AMD).
The additional post-hoc findings were presented at the 14th Annual Vit-Buckle Society (VBS) Meeting.
Wait, didn’t I just recently hear about Ocular Therapeutix in the news?
Indeed. Ocular Therapeutix has been busy since last August with clinical trials for AXPAXLI in both the wet AMD and nonproliferative diabetic retinopathy (NPDR) indications (which now both have Special Protocol Assessments [SPAs]).
- In fact: HELIOS-3 phase 3 trial is currently recruiting and has an estimated primary completion date in March 2027.
Since then: In December the company announced plans to submit a new drug application (NDA) for wet AMD with an accelerated review period using data from two phase 3 trials:
- SOL-1 (NCT06223958)
- SOL-R (NCT06495918)
And most recently: In February, Glance reported positive topline findings from SOL-1 (the same study) …. which we will dig more into in a moment.
Give me a refresher on AXPAXLI.
AXPAXLI is an investigational, bioresorbable hydrogel intravitreal (IVT) implant formulated with anti-angiogenic properties.
What it does: Provides a continuous delivery of an FDA-approved small-molecule, multi-target tyrosine kinase inhibitor (TKI) known as axitinib.
- Its delivery mode: An IVT-administered 25G needle with a 9-to-12-month target release
As for its proposed retinal indications (other than wet AMD):
- Diabetic macular edema (DME)
- Nonproliferative diabetic retinopathy (NPDR)
- Other vascular endothelial growth factor (VEGF)-mediated retinal diseases
Explain how this implant releases axitinib.
For more information, click here to learn about the company’s proprietary and patented ELUTYX technology platform.
Plus: ELUTYX may sound familiar because it is also used in Ocular Therapeutix’ commercial product DEXTENZA (dexamethasone ophthalmic insert 0.4 mg) for the treatment of ocular inflammation and pain following ophthalmic surgery.
Now let’s move on to SOL-1.
SOL-1 is one of three total registrational trials in the phase 3 SOL program designed to showcase durability, repeatability, and flexibility as follows:
- SOL-1: Superiority study comparing AXPAXLI and aflibercept 2 mg at Week 36
- Estimated primary completion date: April 29, 2026
- SOL-R: Non-inferiority study comparing AXPAXLI Q24W dosing (i.e., every 24 weeks) to aflibercept 2 mg dosed every 8 weeks
- Estimated primary completion date: January 2027
- SOL-X: Open-label extension study designed to evaluate safety and disease-modifying potential of AXPAXLI
And the purpose behind SOL-1?
The study aims to enable more infrequent IVT dosing of AXPAXLI, ideally every 6 months to (potentially) every 12 months (in other words: 1 to 2 injections per year).
How: By evaluating a single injection of AXPAXLI (versus a single aflibercept 2 mg injection) among randomized newly-diagnosed wet AMD patients.
- Check out our recent coverage of the trial for a deeper dive into the study design, methodology, and clinical data.
Also, keep in mind: SOL-1 is operating under a Special Protocol Assessment (SPA).
And what of this new data?
Broadly, AXPAXLI demonstrated a “strong overall efficacy profile with unmatched durability.”
- How: Achieving statistical significance in the first three of five key secondary endpoints tested in hierarchical order.
- Plus: Six other pre-specified secondary endpoints measuring clinically significant functional and anatomic outcomes were met with statistical significance.
And how did AXPAXLI perform in terms of sustained disease control?
Subjects in the AXPAXLI arm had significantly lower risk in anatomic worsening from Week 8 compared to the aflibercept (2 mg) arm
- Median time to ≥30 μm central subfield thickness (CSFT) increase
- AXPAXLI cohort: 39 weeks
- Aflibercept 2 mg cohort: 16 weeks (a 23-week difference!)
- Estimated hazard ratio (HR): 0.7 (descriptive p<0.0001)
- Median time to ≥75 μm CSFT increase
- AXPAXLI cohort: 46 weeks
- Aflibercept 2 mg cohort: 24 weeks (a 22-week difference!)
- Estimated hazard ratio (HR): 0.5 (descriptive p<0.0001)
And the data on visual outcomes?
Visual acuity gains achieved during the loading phase were generally maintained up to Week 52 with AXPAXLI across screening best-corrected visual acuity (BCVA) quartile subgroups.
- A key finding: The magnitude of vision improvements was influenced by BCVA at screening.
For example: AXPAXLI subjects in the lowest vision quartile group at screening had the greatest visual gains with +11.8 ETDRS letters compared to +8.5 letters in the aflibercept 2 mg arm at Week 52.
In comparison: Subjects in the best vision quartile at screening had essentially no change in vision at Week 52 (-0.5 vs. +1.1 letters; AXPAXLI vs aflibercept) as they started with almost 20/20 vision.
How did visual outcomes in rescue-free participants compare?
The observed difference for change in BCVA from baseline at Week 24 in the rescue-free subjects was -1.9 ETDRS letters in the AXPAXLI arm (+7.5 ETDRS from screening) versus -2.6 letters in the aflibercept arm (+6.0 letters from screening).
Importantly: 81% of the AXPAXLI subjects were rescue-free at Week 24, and 75% of AXPAXLI subjects remained rescue-free at Week 36 while also losing <1 additional letter from Week 24 (+6.6 letters from screening).
And finally … the safety profile.
For all participants in the AXPAXLI cohort who reported a vitreous floater adverse event, the drug particles are no longer visible (mean time of 20 weeks).
The company noted that further analysis continues to illustrate the appearance of floaters corresponds closely to expected hydrogel bioresorption and drug elution without adversely affecting vision.
What did the company say about these findings?
As Pravin U. Dugel, MD, executive chairman, president, and CEO of Ocular Therapeutix stated:
- “A clear drug profile has emerged for AXPAXLI: a product candidate with durability that is unmatched in the wet AMD space while demonstrating excellent sustained disease control.”
On this recent data, Dr. Dugel added that: “This is simply an unprecedented level of sustained disease control and allows us to reimagine the management of wet AMD for patients. These data continue to increase our confidence that AXPAXLI may be adopted broadly and immediately, if approved.”
Next steps?
Ocular Therapeutix remains on track to submit its NDA for AXPAXLI in wet AMD based on the SOL-1 trial alone, subject to planned formal discussions with the FDA—and consistent with recent public commentary.
- For wet AMD: Per the SOL-1 protocol, subjects will be re-dosed again at Week 76 and followed on a masked-basis for safety until the end of Week 104.
- For NPDR: The HELIOS-3 phase 3 trial is currently recruiting and has an estimated primary completion date in March 2027.
What of this FDA commentary?
This planned submission is consistent with recent FDA commentary, which indicated that a single well-controlled phase 3 trial is expected to become the new default standard for approval.
In early April 2026, the FDA Commissioner further noted that this framework is anticipated to be phased in over the next 6 months, highlighting that the same statistical power can be achieved with a well-designed, well-controlled, appropriately powered, single pivotal trial.
As always, stay tuned for developments …