OCS-05 for Acute Optic Neuritis Achieves Key Endpoints in Phase 2 Trial

Riad Sherif, MD

Credit: OIS

OCS-05, an investigational neuroprotective therapy for acute optic neuritis, met its key primary safety endpoint and achieved statistical significance on efficacy-based secondary endpoints in the Phase 2 ACUITY trial.¹

Oculis announced the topline results on January 6, 2025, displaying the peptidomimetic small molecule's favorable safety and tolerability profile versus placebo, in addition to its neuroprotective structural benefit and capability to improve visual function in this population.

“Steroids have been used to treat the inflammation seen in acute optic neuritis, but don’t prevent persistent visual impairments or reduce structural loss,” Mark Kupersmith, MD, a professor and vice chair of translational research at the Icahn School of Medicine at Mount Sinai Hospital, said in a statement. “There remains a critical unmet need for neuroprotective therapies to preserve vision and the potential neuroprotective properties of OCS-05 observed in the ACUITY trial and its impact on visual function could offer significant hope for patients.”

ACUITY was a randomized, double-blind, placebo-controlled, multicenter trial in France evaluating a once-daily intravenous infusion of OCS-05 2 mg/kg or 3 mg/kg or placebo for 5 days in a population with acute optic neuritis receiving steroids. A total of 36 patients with recent onset of unilateral acute optic neuritis with a demyelinating origin were randomized in the trial—33 received treatment and comprised the pre-specified modified intent-to-treat analysis.

For its primary endpoint, the trial measured the percentage of patients with a shift from normal to abnormal in electrocardiogram (ECG) parameters after OCS-05 administration until Day 15 (Visit 4) to determine cardiac safety. Analyses revealed no difference in the percentage of patients with abnormal ECG parameters between the two study arms.

Oculus announced approximately 2 patients in the OCS-05 treatment arms and 1 in the placebo arm shifted from normal to abnormal in any ECG measure between baseline and Day 15 (12.5%). Events in the OCS-05 arms were mild and transient, considered not clinically significant by reviewers in a reading center.

Secondary efficacy endpoints measured the changes in retinal structure using optical coherence tomography, to compare the potential for neuroprotective effects of OCS-05 to placebo. Daily OCS-05 3 mg/kg plus steroid achieved a 43% improvement in ganglion cell-inner plexiform layer (GCIPL) thickness mean change from baseline versus placebo at month 3 (P = .049), which sustained through month 6 (P = .052).

Daily OCS-05 3 mg/kg also demonstrated a 28% improvement in retinal nerve fiber layer (RNFL) thickness mean change from baseline, compared with placebo, at month 3 (P = .045), achieving 30% improvement at month 6 (P = .033). Safety findings reported no drug-related serious adverse events (SAEs) or AEs leading to drug withdrawal or study discontinuation.

Visual function changes were additionally measured, determined by a change in 2.5% ETDRS low contrast letter acuity (LCVA). Results observed a favorable difference in LCVA mean change from baseline at ~18 letters at month 3 (P = .004) and ~15 letters at month 6 (P = .012), compared with placebo.

The US Food and Drug Administration (FDA) previously granted Orphan Drug Designation to OCS-05 for acute optic neuritis, a rare condition without directly approved therapies.² Characterized by acute inflammation and demyelination of the optic nerve, acute optic neuritis affects up to 8 in 100,000 people worldwide, often young adults, and can be the first sign of multiple sclerosis.³

Although steroids attack inflammation and boost recovery in the condition, they cannot provide neuroprotection to prevent vision loss. With further advancement of OCS-05 in acute optic neuritis, Oculis announced a plan to explore the drug in other neuro-ophthalmic indications, citing its potential for a first-in-class neuroprotective treatment option.¹

“These positive safety and efficacy results from ACUITY represent a significant milestone in bringing the first potential neuroprotective treatment in ophthalmology to patients,” Riad Sherif, MD, chief executive officer of Oculis, said in a statement. “The improvement in vision is especially encouraging, and the consistent improvement in retinal structure highlights the therapeutic potential of OCS-05 across multiple ophthalmic and neurological conditions.”

References

1. _{OCULIS announces positive OCS-05 phase 2 acuity trial in acute optic neuritis, met primary safety endpoint and key secondary efficacy endpoints opening development pathways as a potential first-in-class neuroprotective therapy. Oculis. January 6, 2025. Accessed January 6, 2025. https://investors.oculis.com/news-releases/news-release-details/oculis-announces-positive-ocs-05-phase-2-acuity-trial-acute.}
2. _{OCS-05: Acute optic neuritis - symptoms & treatment. Oculis. December 29, 2024. Accessed January 6, 2025. https://oculis.com/our-commitment/acute-optic-neuritis/.}
3. _{Jamali Dogahe S, Pakravan P, Pakravan M. Acute Optic Neuritis: An Update on Approach and Management. J Ophthalmic Vis Res. 2023;18(4):433-440. Published 2023 Nov 30. doi:10.18502/jovr.v18i4.14556}