Oculis' lead candidate fails to meet primary endpoint in Phase III diabetic macular edema trials

Oculis Holding AG (Nasdaq: OCS) reported that OCS-01, its topical eye drop formulation under investigation for diabetic macular edema (DME), failed to meet the primary endpoint in both Phase III DIAMOND trials, dealing a significant blow to the company's DME program and prompting it to abandon plans for an FDA filing in that indication.

The DIAMOND-1 and DIAMOND-2 trials were randomized, double-masked, vehicle-controlled Phase III studies enrolling more than 800 patients across 119 sites in the United States and several other countries. Both trials evaluated OCS-01 eye drops against vehicle over 52 weeks, with the primary endpoint defined as mean change in best corrected visual acuity ETDRS letter score from baseline to week 52. Neither trial met that endpoint. The key secondary endpoint — the proportion of patients achieving a gain of 15 or more letters in BCVA — was also not met in either study. Retinal thickness reduction, measured by optical coherence tomography, did show a substantial and persistent reduction with OCS-01 versus vehicle across all visits in DIAMOND-2, and at all visits except week 52 in DIAMOND-1, suggesting biological activity at the anatomical level that did not translate into functional visual improvement. No specific numerical values for letter score changes or retinal thickness measurements were disclosed in the topline release. OCS-01 was well tolerated, with no unexpected adverse events and a safety profile consistent with earlier trials.

Competitive context

The outcome highlights the longstanding challenge of delivering therapeutically meaningful drug concentrations to the retina through topical administration, an obstacle that has limited the success of numerous retinal eye drop programs despite encouraging preclinical and anatomical findings

The DME treatment landscape is dominated by intravitreal anti-VEGF agents — including Regeneron's Eylea HD (aflibercept 8 mg), Roche's Vabysmo (faricimab), and Roche's Susvimo (ranibizumab delivered via a port delivery system) — all of which have demonstrated robust BCVA gains in pivotal trials. OCS-01's topical drop formulation was designed to offer a non-injectable alternative, a meaningful convenience proposition in a field where injection burden remains a practical barrier. The failure to demonstrate BCVA benefit, despite anatomical signal, mirrors a recurring challenge in DME drug development: retinal thickness reduction does not reliably predict visual acuity outcomes, particularly over longer time horizons. Cross-trial comparisons are limited by differences in patient populations, baseline characteristics, and trial design, but the absence of a functional endpoint signal in two adequately powered Phase III studies leaves little room for a regulatory path forward in DME. Oculis said it does not plan to pursue an FDA filing for OCS-01 in that indication.

The company held USD 278 million in cash, cash equivalents, and short-term investments as of March 31, 2026, and said that runway extends into the second half of 2029. It will now concentrate resources on privosegtor, a neuroprotective candidate in the PIONEER registrational program targeting optic neuropathies including optic neuritis and non-arteritic anterior ischemic optic neuropathy, and on licaminlimab, a topical anti-TNFα in the PREDICT-1 registrational trial for dry eye disease. For investors, both of these programs now assume greater importance in Oculis' value proposition following the loss of its lead late-stage retinal program.

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