Ocular Therapeutix Initiates HELIOS-3 Phase 3 Trial for AXPAXLI in Diabetic Retinopathy
Key Insights
Ocular Therapeutix has randomized the first patient in HELIOS-3, a Phase 3 registrational trial evaluating AXPAXLI for non-proliferative diabetic retinopathy (NPDR).
The HELIOS program comprises two complementary superiority studies targeting a broad diabetic retinopathy label, with AXPAXLI potentially offering treatment as infrequent as every 12 months.
Despite over 6 million NPDR patients in the U.S., fewer than 1% currently receive therapy due to the burden of frequent injections in this working-age population.
Ocular Therapeutix has announced the randomization of the first patient in its HELIOS-3 Phase 3 registrational trial for AXPAXLI (OTX-TKI) in non-proliferative diabetic retinopathy (NPDR), marking a significant milestone in addressing a major unmet medical need in diabetic eye disease.
The HELIOS-3 trial represents the second component of Ocular's comprehensive registrational program, working alongside HELIOS-2 to target a broad diabetic retinopathy label. Both studies are designed as global, complementary superiority trials utilizing a novel ordinal diabetic retinopathy severity scale (DRSS) primary endpoint.
Addressing Critical Treatment Gap
The initiation of HELIOS-3 addresses a substantial treatment gap in diabetic retinopathy care. According to Pravin U. Dugel, MD, Executive Chairman, President and Chief Executive Officer of Ocular Therapeutix, "While there are more than 6 million NPDR patients in the U.S., fewer than 1% receive therapy today, due mostly to the burden of frequent injections in this working age population."
AXPAXLI's potential to deliver efficacy with attractive durability could help hundreds of thousands, if not millions more patients preserve vision. The treatment approach aims to provide therapy as infrequent as every 12 months, representing a significant departure from current treatment paradigms that require frequent intravitreal injections.
HELIOS Program Design
The HELIOS program consists of two complementary superiority studies designed to evaluate whether early AXPAXLI treatment can meaningfully alter the course of NPDR. HELIOS-2 is a superiority study comparing AXPAXLI dosed every 12 months to ranibizumab (0.3 mg) in approximately 432 subjects with moderately severe to severe NPDR without center-involved diabetic macular edema (CI-DME).
HELIOS-3 is structured as a multi-center, double-masked, randomized (1:1:1), three-arm study comparing 6- and 12-month dosing regimens of AXPAXLI to sham in approximately 930 subjects. The first arm receives AXPAXLI at Day 1 and re-dosing at Week 24, the second arm receives AXPAXLI at Day 1 and sham at Week 24, while the third arm receives sham at both timepoints.
Both studies utilize a novel ordinal ≥2-step diabetic retinopathy severity score (DRSS) primary endpoint assessed at Week 52. Ocular has aligned with the FDA on this novel ordinal DRSS endpoint through its Special Protocol Assessment (SPA) agreement for HELIOS-2.
Clinical Innovation and Regulatory Alignment
The novel ordinal ≥2-step DRSS endpoint represents an important advancement for the retina field. As noted by Dilsher S. Dhoot, MD, of California Retina Consultants, "Unlike binary endpoints, this ordinal measure captures changes across the full DRSS spectrum, including improvement, stability, and progression. By allowing every patient to contribute to the primary analysis, it enables more efficient trials while generating clinically meaningful data."
Allen Hu, MD, Principal Investigator at Cumberland Valley Retina Consultants, emphasized the clinical significance: "Current DR treatments are burdensome and unsustainable – particularly for this working age population, unlike wet AMD – requiring numerous intravitreal injections every year. This limits treatment uptake, leaving many at risk for disease progression and irreversible vision loss."
Promising Early Results
The HELIOS program builds on encouraging data from HELIOS-1, which demonstrated stability or improvement in the DRSS with generally good tolerability. Notably, no patients in the AXPAXLI arm developed proliferative diabetic retinopathy (PDR) or center-involved diabetic macular edema through week 48, while 37.5% of patients in the sham control arm developed PDR or CI-DME through the same timeframe.
The HELIOS-1 results showed that 23.1% of patients in the AXPAXLI arm had a 2-step or greater DRSS improvement, and 46.2% had a 1- or 2-step or greater DRSS improvement at 48 weeks. Importantly, the DRSS did not worsen at 48 weeks in any patients in the AXPAXLI arm.
Drug Profile and Mechanism
AXPAXLI is an investigational, bioresorbable, intravitreal hydrogel incorporating axitinib, a small molecule, multi-target, tyrosine kinase inhibitor with anti-angiogenic properties. The drug is currently being evaluated for wet age-related macular degeneration, diabetic retinopathy, and other retinal diseases, leveraging Ocular's proprietary ELUTYX bioresorbable hydrogel-based formulation technology.
The comprehensive approach targeting both NPDR and patients with non-center-involved diabetic macular edema (non-CI-DME) positions AXPAXLI for a potentially broad diabetic retinopathy label that could span the full continuum of disease.