ONL1204, a novel ophthalmic solution, has demonstrated potential in improving visual acuity for patients with macula-off rhegmatogenous retinal detachment (RRD), according to Phase 2 clinical trial results presented at the 128th Annual American Academy of Ophthalmology (AAO) Meeting. The study suggests that ONL1204 may offer a clinically significant benefit for patients at risk of vision loss following RRD.
Mechanism of Action
ONL1204 is a first-in-class small peptide designed to inhibit the Fas receptor. By blocking the Fas pathway, ONL1204 aims to prevent the activation of immune signaling that leads to the death of key retinal cells, thus mitigating vision loss associated with RRD. RRD involves the separation of the neurosensory retina from the retinal pigment epithelium and choroid, resulting in oxygen and nutrient deprivation and subsequent tissue damage.
Phase 2 Trial Design and Results
The Phase 2 study was a randomized, single-masked trial involving 235 patients with macula-off RRD. Participants were assigned to receive either 50 mg or 200 mg of ONL1204, or a sham treatment, administered as a single intravitreal injection prior to RRD repair. The primary outcome measure was contrast sensitivity at Week 24, with assessments conducted postoperatively over a 6-month follow-up period.
While the primary endpoint of contrast sensitivity did not differ significantly between the three groups, a notable visual acuity benefit was observed in a specific subgroup. Patients with macula-off status of 8 days or more who received ONL1204 showed a 1-2 line improvement in visual acuity at Week 24 compared to the sham group. According to Durga S. Borkar, MD, assistant professor of ophthalmology at Duke University Eye Center, this improvement is clinically meaningful for patients who do not fully recover vision after retinal detachment surgery.
"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," Dr. Borkar told HCPLive.
Impact of Macula-Off Duration
An important observation from the study was the impact of macula-off duration on visual outcomes. The ONL1204 200 mg arm had a slightly longer average duration of macula-off status prior to surgery (8.8 days) compared to the sham arm (7.2 days). This difference may have influenced the overall visual outcomes, as noted by Dr. Borkar.
Next Steps
Further analysis of the Phase 2 data, including pre-specified subgroup analyses, is planned. The results will be prepared for publication, and discussions with the FDA are anticipated for an End-of-Phase 2 meeting to determine the future development pathway for ONL1204.
