Ocular Therapeutix Randomizes First Patient in HELIOS-3 Phase 3 Study for AXPAXLI in NPDR

Ocular Therapeutix has announced the randomization of the first patient in HELIOS-3, the second Phase 3 registrational study evaluating AXPAXLI (OTX-TKI) for the treatment of nonproliferative diabetic retinopathy (NPDR). The HELIOS clinical program is designed to assess AXPAXLI’s potential in providing long-lasting treatment effects with less frequent dosing.

HELIOS Program Structure and Study Design

The HELIOS program includes two complementary superiority trials:

       • HELIOS-2: Compares AXPAXLI administered every 12 months to ranibizumab (0.3 mg)

       • HELIOS-3: Compares 6- and 12-month dosing of AXPAXLI to sham treatment

Both studies use a novel ordinal ≥2-step diabetic retinopathy severity score (DRSS) as the primary endpoint. This endpoint is designed to evaluate whether infrequent treatment with AXPAXLI can significantly impact the progression of NPDR.

Company Perspective on AXPAXLI’s Role in Diabetic Retinopathy

According to Pravin U. Dugel, MD, Executive Chairman, President, and CEO of Ocular Therapeutix, the initiation of HELIOS-3 is a key step in the development of AXPAXLI:

“Initiating the HELIOS registrational program marks a pivotal step toward redefining treatment for diabetic retinal disease. AXPAXLI’s potential to deliver efficacy with attractive durability could help hundreds of thousands, if not millions more patients preserve vision.”

“By aiming for a superiority-based DR label that spans the full continuum of disease—including NPDR and DME—we believe AXPAXLI could deliver a market opportunity that is not merely incremental, but transformative for patients, physicians, and payors around the world.”

Investigator Commentary: Addressing Treatment Burden

Allen Hu, MD, Principal Investigator at Cumberland Valley Retina Consultants, commented on the relevance of the HELIOS program in clinical practice:

“The HELIOS program has the potential to transform care for patients with diabetic retinal disease. Current DR treatments are burdensome and unsustainable – particularly for this working age population, unlike wet AMD – requiring numerous intravitreal injections every year.”

“AXPAXLI shows significant promise to address the unmet need for an effective treatment with durable efficacy, based on the encouraging HELIOS-1 data. Given the rapid enrollment and outstanding execution of the SOL studies for AXPAXLI in wet AMD, I have full confidence that the Ocular clinical team will deliver another highly successful program in NPDR.”

Use of Ordinal DRSS Endpoint in Clinical Trials

The HELIOS studies introduce an ordinal ≥2-step DRSS endpoint, which differs from traditional binary endpoints. Dilsher S. Dhoot, MD, of California Retina Consultants, discussed the significance of this approach:

“This new DRSS endpoint reflects clinical goals more effectively and may offer greater sensitivity in capturing changes in disease severity. Unlike binary measures, it evaluates improvement, stability, and progression, allowing every patient to contribute to the analysis.”

“If the HELIOS trials are successful, I expect AXPAXLI will be widely adopted across diabetic retinal disease due to its potential for durable efficacy and low treatment burden, making it highly attractive to patients, physicians, and payors alike.”