Ocular Therapeutix, Inc. has officially kicked off its latest phase 3 clinical trial (SOL-R) on AXPAXLI (axitinib intravitreal implant) for wet age-related macular degeneration (AMD).
Give me a rundown on AXPAXLI.
AXPAXLI (previously referred to as OTX-TKI) is an investigational, preservative-free, bioresorbable hydrogel intravitreal implant with anti-angiogenic properties.
Its intent: The intravitreal implant is designed to continuously deliver axitinib (a small-molecule, multi-target tyrosine kinase inhibitor [TKI]) for the following indications:
- Wet AMD
- Diabetic retinopathy (DR)
- Other vascular endothelial growth factor (VEGF)-mediated retinal diseases
And its delivery mechanism?
AXPAXLI will be administered via a 25G needle using the proprietary ELUTYX technology platform.
- About the platform: A bioresorbable polymer matrix hydrogel developed to provide localized, sustained-release drug delivery.
With a 9 to 12-month target release, the implant is intended to provide a targeted drug delivery while also minimizing systemic exposure.
What’s the clinical data on it thus far?
There’s been a few trials… for both AMD and DR.
In June 2024, the company reported positive 48-week data from a phase 1 trial evaluating AXPAXLI for non-proliferative DR (NPDR).
- Overall: AXPAXLI was found to be well-tolerated, with AXPAXLI-treated patients demonstrating improvements in central subfield thickness (CST) and ≥2-step Diabetic Retinopathy Severity Scale (DRSS) vs sham-treated patients. Read our coverage.
Prior to that, in June 2023, the company reported 12-month, phase 1 topline data on AXPAXLI for wet AMD.
- Those findings: A sustained best corrected visual acuity (BCVA) was continuously noted for AXPAXLI-treated patients (mean change from baseline = -1.0 letters) as well as a sustained CST (mean change from baseline = +20.2 μm) vs sham-treated (aflibercept) patients.
Alrighty, now let’s talk about this phase 3 SOL-R study.
First: Don’t confuse this trial with the company’s first phase 3 trial: SOL-1 (NCT06223958), currently being conducted in an estimated 300 treatment-naïve wet AMD patients.
Next: The phase 3 SOL-R study (NCT06495918) is a global, multicenter, double-masked, randomized, parallel group, non-inferiority trial evaluating the use of AXPAXLI for treating an estimated 825 patients (aged 50+) with wet AMD.
Participant criteria?
Participants must have been diagnosed with treatment naïve juxtafoveal and/or subfoveal neovascularization (SFNV) secondary to wet AMD (3 months prior to screening).
- Plus: Received up to two monthly injections of 2 mg aflibercept, with the last injection an estimated 4 weeks prior to screening
And the study design?
Three arms are being evaluated among wet AMD patients:
- Repeat dosing of AXPAXLI when injected every 6 months (Q6M)
- Intravitreal dose of 2 mg aflibercept every 8 weeks (Q8W)
- Intravitreal dose of 8 mg aflibercept Q6M
Essentially: SOL-R investigators are analyzing AXPAXLI compared to the current standard of care (aflibercept) administered in a repeat-dosing regimen (aka: “real-world” requirements), according to Ocular Therapeutix.
What’s being measured?
The primary outcome is best-corrected visual acuity (BCVA), as measured by the mean change from baseline at Week 48.
So what’s the difference between the SOL-1 and SOL-R trials?
Pravin U. Dugel, MD, Ocular Therapeutix’s executive chairman, president, and CEO, noted that the “real-world” experience plays a key role in SOL-R. “SOL-1 is intended to show that AXPAXLI can safely and reliably maintain visual acuity in patients with wet AMD,” Dr. Dugel stated.
Conversely: “SOL-R is intended to build on that by providing physicians with important evidence regarding the potential to re-dose AXPAXLI every 6 months,” he added.
And with these SOL-1/-R studies?
The real-world component of AXPAXLI dosing included in the SOL-R study may prove to be advantageous for generating “valuable evidence to determine the ultimate durability of a single AXPAXLI implant,” according to Arshad M. Khanani, MD, MA, FASRS, principal investigator of the ongoing SOL-1 trial. He concluded: “Together, these trials aim to provide a comprehensive picture of the flexibility of dosing intervals to meet individual patient needs.”
So when can we expect data?
Clinical Trials reports the SOL-R study isn’t slated to conclude until January 2027.
As for SOL-1: That study is expected to conclude in September 2027.
However, interim data will likely be released in the meantime … so stay tuned.
And the overarching significance of this treatment?
From a big picture perspective, AXPAXLI has the potential to fill the unmet need for a retinal disease treatment (wet AMD) that provides efficacy with just a single injection—and extends beyond 3 to 4 months.