Durga Borkar, MD: Phase 2 Results of ONL1204 for Rhegmatogenous Retinal Detachment

ONL1204 ophthalmic solution achieved similar effects on contrast sensitivity to sham but showed some visual acuity benefit for patients with macula-off rhegmatogenous retinal detachment (RRD) most at risk for vision loss, according to late-breaking data presented at the 128th Annual American Academy of Ophthalmology (AAO) Meeting.¹

In an interview with HCPLive, presenter Durga S. Borkar, MD, an assistant professor of ophthalmology, at Duke University Eye Center, described how the unique mechanism of ONL1204 can potentially provide some visual acuity benefit for patients with macula-off status ≥8 days.

“We saw a visual acuity benefit of ONL1204 in patients with macula-off status of greater than 8 days, and we saw the most effect in patients who were pseudophakic because post-vitrectomy cataracts were not an issue,” Borkar told HCPLive.

RRD is a separation of the neurosensory retina from the retinal pigment epithelium and the choroid, leading to the loss of oxygen and nutrient supply, and ultimately, the death of the tissue.² ONL1204 ophthalmic solution is a novel, first-in-class small peptide that inhibits the Fas receptor, blocking the activation of the Fas pathway and related immune signaling leading to the death of key retinal cells and vision loss.¹

The Phase 2, real-world study randomly assigned patients with macula-off RRD to two doses of ONL1204 50 mg or 200 mg, or sham, administered as a single intravitreal injection before RRD repair. Assessments were performed at a standard routine pace postoperatively and patients were followed for 6 months, with the main outcome being contrast sensitivity at Week 24.

A total of 235 patients were randomized, with a mean age of approximately 60 years and similar baseline visual acuity between study cohorts. In the single-masked study, the duration of macula-off status before surgery was nearly 1.5 days longer in the ONL1204 200 mg arm, compared with the sham arm. According to Borkar, this could have impacted visual outcomes.

“The duration of macula-off status is very relevant to these visual outcomes,” Borkar said. “In the ONL1204 200 mg, the average duration of macula-off status prior to surgery was 8.8 days, compared with 7.2 days in the sham arm.”

Overall, the primary endpoint of contrast sensitivity was the same across all 3 groups, but the visual acuity benefit of ONL1204 was observed for patients with macula-off status ≥8 days and in those who were pseudophakic.

In this subgroup, a 1-2 line improvement in visual acuity was identified at Week 24, compared with sham, which Borkar indicated as clinically significant for patients who do not fully recover vision after retinal detachment surgery.

“The next steps are to continue to analyze this data, perform additional pre-specific subgroup analyses, and publish both these primary results and additional results,” Borkar told HCPLive. “There are also plans to meet with the FDA for an End-of-Phase 2 meeting.”

Disclosures: Relevant disclosures for Borkar include

References

1. _{Borkar DS. Intravitreal Fas inhibitor ONL1204 for Macula-off Rhegmatogenous Retinal Detachment: Phase 2 Clinical Trial Results. Poster presented at American Academy of Ophthalmology (AAO) 2024 Meeting. Chicago, Illinois. October 18-21, 2024.}
2. _{Blair K, Czyz CN. Retinal Detachment. [Updated 2024 Feb 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK551502/}