Dilsher Dhoot, MD: Interim Results on OTX-TKI for NPDR in HELIOS

Interim results from the Phase 1 HELIOS trial demonstrate the tolerability and efficacy of sustained-release Axitinib Implant (OTX-TKI) for moderately severe to severe non-proliferative diabetic retinopathy (NPDR) at 48 weeks.

These late-breaking data on 0.6 mg OTX-TKI, presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting, showed stability or improvement in Diabetic Retinopathy Severity Scale (DRSS), without worsening, and remained generally well-tolerated in all treated eyes with NPDR.

“I think the data presented today is compelling, and look forward to larger trials looking at OTX-TKI, which could potentially be a durable, 1–2 injection per year treatment for patients with moderately severe and severe NPDR to help prevent complications in a proactive fashion,” presenting investigator Dilsher S. Dhoot, MD, California Retina Consultants, told HCPLive.

Moderately severe and severe subtypes of NPDR threaten vision for patients, but anti-vascular endothelial growth factor (VEGF) treatment initiation is often delayed until later disease stages. A need for frequent intravitreal anti-VEGF injections and its correlated high treatment burden is a known barrier, leaving a large unmet need for more durable treatments.

HELIOS is a multi-center, double-masked, 2:1 randomized parallel-group clinical trial conducted at 10 US centers. Interim results were based on 21 evaluable subjects of 22 enrolled participants after a single patient died from an event unrelated to the study drug. Patients had moderately severe to severe NPDR and a baseline visual acuity of ≥69 ETDRS letters in the study eye.

Patients could not have received anti-VEGF treatment or dexamethasone intravitreal implant in the previous 12 months or intraocular steroid injections within the prior 4 months. HELIOS’ primary outcome was the safety and tolerability of OTX-TKI, with secondary outcomes including changes in DRSS scores, best-corrected visual acuity (BCVA), and central subfield thickness (CST).

Upon analysis, OTX-TKI showed no incidence of investigational product-related intraocular inflammation, iritis, vitritis, or vasculitis. Overall, no serious ocular adverse events were reported.

At 48 Weeks, 46.2% (n = 13) of OTX-TKI-treated eyes had a 1- or 2-step improvement in DRSS, compared with 0% (n = 8) in the sham-treated arm. None of the OTX-TKI-treated eyes had a worsening in DRSS, compared with 25% of the sham arm.

Approximately 37.5% of eyes in the sham arm and 0% in the OTX-TKI arm developed vision-threatening complications, including center-involved DME (CI-DME) or proliferative diabetic retinopathy (PDR). Overall, a single injection of OTX-TKI exhibited durable DRSS improvement for up to 48 weeks.

“We see individual examples of those patients in the OTX-TKI arms having improvement in non-centered DME and this was encouraging to see across the board relative to sham, where we saw worsening in the examples presented,” Dhoot told HCPLive.

Disclosures: Relevant disclosures for Dhoot include Apellis, Genentech, Ocular Therapeutix, Regeneron, and others.

Reference

_{Dhoot DS. Interim Safety and Efficacy Results From the Phase 1 HELIOS Trial of Sustained-Release Axitinib Implant (OTX-TKI) for NPDR. Paper presented at the American Society of Retina Specialists (ASRS) 42nd Annual Meeting. Stockholm, Sweden. July 17-20, 2024.}