The FDA has agreed to modify a Special Protocol Assessment (SPA) for Ocular Therapeutix, Inc.’s pivotal phase 3 clinical trial on AXPAXLI (aka OTX-TKI) for the treatment of wet age-related macular degeneration (AMD).
First, tell me about AXPAXLI.
AXPAXLI (axitinib intravitreal implant) is an investigational, bioresorbable hydrogel intravitreal implant with anti-angiogenic properties which has been designed to continuously deliver axitinib (a small molecule, multi-target tyrosine kinase inhibitor [TKI]) for wet AMD.
It is also currently in development for the potential treatment of:
- Diabetic retinopathy (DR) (for details on the phase 1 HELIOS trial, click here)
- Other vascular endothelial growth factor (VEGF)-mediated retinal diseases
How would the implant be delivered?
The intravitreal implant would deliver axitinib using Ocular Therapeutix’s proprietary ELUTYX technology platform—a bioresorbable polymer matrix hydrogel developed to provide localized, sustained drug delivery.
AXPAXLI is administered via a 25G needle, with a target release of 9 to 12 months.
Clinically speaking, how has it performed so far?
Data from a phase 1 trial (NCT04989699) released promising results in June 2023 demonstrating the safety, durability, and efficacy of the axitinib implant when compared to aflibercept injections. Details here.
Now this phase 3 trial.
The multicenter, double-masked, randomized, parallel-group, superiority-designed pivotal SOL phase 3 trial is set to enroll an estimated 300 patients with wet AMD who are treatment naïve in the study eye.
Participants will randomly receive either one injection of aflibercept or one AXPAXLI implantfollowed by an as-needed supplemental anti-VEGF treatment.
What are the outcome measures?
According to the study plan for the SOL trial (NCT06223958) via:
- Best-corrected visual acuity (BCVA) up to 36 weeks
- Incidence and severity of treatment emergent adverse events (AEs) up to 104 weeks
Now how does this modification come into play?
The SPA Agreement Modification allows the study to include treatment-naïve wet AMD participants with a VA of approximately 20/80 or better at their initial screening visit, according to the company.
Further, “After two aflibercept injections in the screening period, eligible participants would need to gain at least 10 [Early Treatment Diabetic Retinopathy Study] ETDRS letters from the initial screening visit to Day 1 or achieve a visual acuity of approximately 20/20 or better at Day 1, in addition to satisfying other criteria, to qualify for enrollment in the trial.”
Interesting… anything else?
The modification also enables the study to evaluate AXPAXLI with a single optimized configuration containing a drug load of 450 µg of a more soluble form of axitinib.
And the resulting effect of this?
Per Ocular Therapeutix, this “optimized configuration” is intended to allow for a slightly increased daily release of the molecule, as well as to improve the “synchronization” of axitinib drug depletion with hydrogel bioresorption.
So why modify the SPA?
Based on the modifications, “we believe we can accelerate the enrollment process for the SOL trial,” stated CEO Antony Mattessich.
And with this ramp up to enroll study participants, topline data from the study may become readily available sooner.
And lastly… give me the bigger picture on this.
Based on data thus far, AXPAXLI has shown the potential to deliver efficacy extending beyond 3 to 4 months with a single implant.
Translation, the medication could reduce the amount of injections and follow-up visits necessary on a yearly basis for wet AMD patients dependent on the level of severity.