RELIEF: Licaminlimab Improves Signs of Dry Eye Disease in Phase 2b Trial

Topline results from the Phase 2b RELIEF trial demonstrated the positive effects of licaminlimab, a novel anti-TNFα biologic eye drop, on multiple signs of dry eye disease (DED).¹

Announced by Oculis on June 10, 2024, improvements in prespecified efficacy endpoints were identified in the full study population, but with predictive and more pronounced effects in the TNFR1-related genetic biomarker population.

“The precision medicine approach with licaminlimab could be a groundbreaking paradigm shift in ophthalmology and the treatment of DED,” said Eric Donnenfeld, MD, clinical professor of ophthalmology at New York University and chair of the Oculis Cornea Scientific Advisory Board.¹ “The current approach of ‘trial and error’ and our inability to predict response for this highly heterogenous population leads to a low level of patient satisfaction.”

The dual anti-inflammatory and anti-necrotic mechanism of action of TNF-α inhibition has been well-established in ocular inflammatory diseases, with notable improvement in disease management and treatment outcomes.² Across Phase 2 trials, licaminlimab has benefited both the signs and symptoms of DED and remained well-tolerated.³

Phase 2 data have also identified a genetic biomarker that revealed a clear correlation between this variant in the TNFR1 gene and improved response to licaminlimab.

RELIEF is a multi-center, randomized, double-masked, vehicle-controlled trial evaluating the efficacy and safety of licaminlimab in 122 patients with DED (62 to licaminlimab; 60 to vehicle). A subpopulation of patients (n = 23) with TNFR1-related genotypes was specifically evaluated as prespecified in the protocol.

These patients were measured for efficacy endpoints at baseline, Day 15, and Day 43. The prespecified investigational efficacy endpoints involved multiple DED signs accepted by the US Food and Drug Administration (FDA).

Across the full trial population, the treatment effect in favor of licaminlimab was identified for multiple sign endpoints, including fluorescein staining in the total cornea, inferior corneal, central corneal, and nasal conjunctival regions, and in the Schirmer’s test.

Among the subpopulation with the TNFR1 genetic biomarker, licaminlimab’s treatment effect was found in multiple sign endpoints, including fluorescein staining in the total cornea, inferior corneal, central corneal, nasal conjunctival, total conjunctiva, and total ocular surface regions, in the Schirmer’s test, and conjunctival redness.

A rapid treatment effect on corneal inflammation was seen as early as Day 15 and achieved statistical significance at Day 43 with licaminlimab. The mean change from baseline versus vehicle in the inferior corneal fluorescein staining score was –0.59 (95% CI, –1.165 to –0.017), with an increased treatment effect over time.

“To my knowledge, licaminlimab is the first DED medication to demonstrate in a clinical trial a predictive treatment effect in patients with a common genetic biomarker to potentially solve this problem,” Donnenfeld added.¹

Safety results showed licaminlimab remained well-tolerated, with an 11.5% and 10.2% incidence of ocular treatment-emergent adverse events (TEAEs) in the licaminlimab and vehicle groups, respectively. TEAEs in the fellow eye were similar to the study eye and no serious adverse events were identified with licaminlimab during the study period.

Oculus announced its intention to meet with the FDA for an end-of-Phase 2 meeting to discuss the registration path for licaminlimab in DED and finalize Phase 3 development plans.¹

“We are pleased that we achieved all of our objectives for the trial, and extremely encouraged to see licaminlimab’s profound results with a precision medicine approach which has the potential to transform the way we develop drugs and treat patients in ophthalmology,” said Riad Sherif, MD, chief executive officer of Oculis.¹

References

1. _{Oculis announces positive topline results of phase 2B relief trial with Licaminlimab, designed to transform the treatment paradigm of dry eye disease with a precision medicine strategy. Oculis. June 10, 2024. Accessed June 10, 2024. https://oculis.gcs-web.com/news-releases/news-release-details/oculis-announces-positive-topline-results-phase-2b-relief-2.}
2. _{Mirshahi A, Hoehn R, Lorenz K, Kramann C, Baatz H. Anti-tumor necrosis factor alpha for retinal diseases: current knowledge and future concepts. J Ophthalmic Vis Res. 2012;7(1):39-44.}
3. _{Oculis announces publication of PH2 data showing topical anti-tnfα agent Licaminlimab OCS-02 relieves ocular discomfort in Ded. Oculis. August 23, 2022. Accessed June 10, 2024. https://oculis.gcs-web.com/news-releases/news-release-details/oculis-announces-publication-ph2-data-showing-topical-anti-tnfa.}