Oculis Shelves FDA Filing After Phase 3 DME Trials Miss Key Vision Goals

Key Points

• Oculis’ Phase 3 DIAMOND trials of OCS-01 in diabetic macular edema missed both the primary vision endpoint and the key secondary endpoint, so the company says it does not currently plan to file for FDA approval in that indication.
• Despite the failure on vision outcomes, Oculis said OCS-01 showed a rapid and sustained reduction in retinal thickness and had a safety profile consistent with prior studies, with no unexpected safety findings.
• The company is shifting focus to its other late-stage programs, especially Privosegtor and licaminlimab, and says its $278 million cash position gives it runway into the second half of 2029.

Oculis NASDAQ: OCS said its two Phase 3 DIAMOND trials of OCS-01 in diabetic macular edema did not meet their primary endpoints, and the company does not currently plan to pursue a U.S. Food and Drug Administration filing for the drug candidate in that indication.

Chief Executive Officer Riad Sherif said on the company’s conference call that Oculis was “naturally disappointed” with the outcome of the DIAMOND-1 and DIAMOND-2 studies. Both trials evaluated OCS-01 against vehicle in patients with diabetic macular edema, or DME, with the primary endpoint measured by change in best-corrected visual acuity, or BCVA, at week 52.

“Despite showing a rapid, substantial, and sustained reduction in retinal thickness in patients treated with OCS-01,” Sherif said, the primary endpoint and the key secondary endpoint for vision gain were not met in either study at week 52.

DIAMOND Trials Miss Vision Endpoints

The DIAMOND program consisted of two similarly designed, multicenter global Phase 3 studies. DIAMOND-1 randomized 404 patients, while DIAMOND-2 randomized 401 patients, with roughly 200 patients per treatment arm. Sherif said more than 80% of patients completed the drug portion of the 52-week study, which included a six-week induction phase and a 46-week maintenance phase.

The trials enrolled adults with DME associated with type 1 or type 2 diabetes. The primary endpoint was change in BCVA ETDRS letter score at week 52, while the key secondary endpoint was the percentage of patients gaining at least 15 letters in BCVA at week 52. Another secondary endpoint examined change in central subfield thickness, or CST.

Sherif said the active treatment arm showed a “rapid and sustained reduction” in retinal thickness through week 52, an anatomical measure that he described as objective evidence of drug effect in the retina. However, that did not translate into the functional improvement required for the trials to succeed on BCVA endpoints.

Company Points to Unexpected Vehicle Response

During the question-and-answer portion of the call, JPMorgan analyst Tessa Romero asked what factors may have driven the outcome, including the vehicle arm’s performance and variability in the studies.

Sherif said the company had only top-line data available and had not identified a clear reason for the vehicle response. He said the approximately five-letter gain seen in the placebo group was “more than the double of the best placebo response in any other trial” in DME, calling the result surprising. He also noted that DME can be highly variable and that diabetes treatment has changed over time, including the use of GLP-1 products, but said the company did not yet have data to explain the findings.

Asked whether there were trial conduct issues, Sherif said Oculis had cross-checked the quality of protocol execution and found no evidence of an execution problem. He also said compliance was high and in line with the earlier stage of the program, and that the company did not see a meaningful difference between phakic and pseudophakic patients.

Safety Profile and Program Decision

Sherif said OCS-01 was well tolerated, with no unexpected safety findings. The safety profile was consistent with prior trials, he said. Elevated intraocular pressure and cataracts were higher among patients treated with OCS-01, which Sherif said was expected and in line with chronic steroid use in DME.

Based on the results, Oculis said it does not plan at this time to pursue an FDA regulatory filing for OCS-01 in DME. Chief Financial Officer Sylvia Cheung said Oculis owns the OPTIREACH technology and OCS-01 candidate, and there are no license payments tied to the program. She said routine site closeout costs for the DIAMOND program are expected in the second quarter and early third quarter.

In response to a question from Needham & Company analyst Serge Belanger, Sherif said OCS-01 had been prepared for a potential filing in ocular surgery. “We were and we are ready actually to file for ocular surgery,” he said, adding that the company will conduct a full assessment before making a decision.

Focus Shifts to Privosegtor and Licaminlimab

Oculis said it will focus resources on its late-stage portfolio, including the Privosegtor platform and licaminlimab. Sherif cited the company’s $278 million in cash, cash equivalents and short-term investments and said Oculis has a cash runway into the second half of 2029.

For licaminlimab, Oculis is running the PREDICT-1 registration trial in dry eye disease. Sherif said the study is planned to enroll 160 patients in two arms, with a primary endpoint of global ocular discomfort score at day 29 in TNFR1-positive patients. He said about 70% of planned sites are in active screening, and the company expects to provide an update later in the year as screening and randomization progress.

For Privosegtor, the company is advancing the PIONEER program in optic neuropathies. PIONEER-1 and PIONEER-2 are focused on optic neuritis, while PIONEER-3 is focused on non-arteritic anterior ischemic optic neuropathy, or NAION. Sherif said the PIONEER-1 design is aligned with the FDA under a special protocol assessment, and that more than 70 U.S. and international sites are in various stages of activation.

Sherif said Oculis expects to treat the first patient in PIONEER-1 “in the near future” and plans to initiate PIONEER-2 after the company begins randomizing patients in PIONEER-1. He also said Oculis plans to meet with the FDA in the second half of the year to discuss the potential for Privosegtor in multiple sclerosis and to broaden optic neuritis into relapse of MS.

About Oculis NASDAQ: OCS

Oculis SA NASDAQ: OCS is a clinical-stage biopharmaceutical company focused on developing novel ophthalmic therapies designed primarily to treat retinal and neuro-ophthalmic diseases. Leveraging its proprietary technology platforms, Oculis aims to deliver therapeutic agents to the back of the eye through topical or nasal administration, potentially offering an alternative to current intravitreal injections. The company’s pipeline includes OCS-01, a topical dexamethasone formulation targeting diabetic macular edema; OCS-05, a neuroprotective candidate for acute optic neuritis and idiopathic intracranial hypertension; and OC-02, a nasal spray formulation of varenicline for dry eye disease.

Founded in 2016 and headquartered in Basel, Switzerland, Oculis operates research and development facilities across Europe and in the United States, with a presence in Cambridge, Massachusetts.

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