Oculis announces positive topline results of Phase 2b RELIEF trial for patients with DED

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Oculis Holding AG announced positive topline results from its Phase 2b RELIEF trial with licaminlimab (OCS-02), a novel anti-TNFα biologic eye drop with an established dual anti-inflammatory and anti-apoptotic mechanism of action in patients with dry eye disease (DED).

Riad Sherif, MD, CEO of Oculis, pointed out in a news release¹ the company was pleased to have achieved all of its for the trial, and is extremely encouraged to see licaminlimab’s results with a precision medicine approach “which has the potential to transform the way we develop drugs and treat patients in ophthalmology.”

“With this and prior positive results on signs and symptoms, we look forward to discussing these encouraging data with the FDA and advancing this program into Phase 3,” he said.

The company noted in its news release it is planning to conduct an end-of-Phase 2 meeting with the FDA to discuss the registrational path for licaminlimab in DED and finalize the Phase 3 development plan.

The company’s Phase 2b RELIEF trial is a multi-center, randomized, double-masked, vehicle-controlled trial evaluating the efficacy and safety of licaminlimab in subjects with signs of DED (NCT05896670).¹

The trial also evaluated the efficacy and safety of licaminlimab in a subpopulation of subjects with a TNFR1-related genotype as prespecified in the protocol. One hundred and twenty-two (122) patients were randomized 1:1 to either licaminlimab (n=62) or vehicle (n=60) across 4 sites for a 6-week treatment period and a 2-week follow up. A total of 23 patients carried a specific TNFR1-related genotype.¹

The company noted in its news release that patients were evaluated for efficacy endpoints at baseline, Day 15 and Day 43. The prespecified investigational efficacy measures in this trial included multiple signs of DED that are accepted by the FDA as efficacy endpoints.

The Phase 2b RELIEF trial showed positive effects on multiple signs of DED:

• For the full trial population (n=122):
  • Treatment effect favoring licaminlimab was observed in multiple sign endpoints including fluorescein staining in the total cornea, inferior corneal, central corneal and nasal conjunctival regions, and in the Schirmer’s test.
• For the subpopulation of patients with the TNFR1 genetic biomarker (n=23):
  • Treatment effect favoring licaminlimab was observed in multiple sign endpoints including fluorescein staining in the total cornea, inferior corneal, central corneal, nasal conjunctival, total conjunctival and total ocular surface regions, in the Schirmer’s test, and in conjunctival redness.
  • Rapid and favorable treatment effect in favor of licaminlimab on corneal inflammation was observed as early as Day 15 that was significant at Day 43, as measured by the difference in mean change from baseline versus vehicle for inferior corneal fluorescein staining score: -0.59 (CI: -1.165, -0.017). The treatment effect also increased over time.

Moreover, the company noted that licaminlimab was well tolerated. The incidence of ocular TEAEs in the study eye was 11.5% in the licaminlimab group and 10.2% in the vehicle group. TEAEs in the fellow eye were similar to the study eye. All ocular TEAEs were mild and transient, and there were no serious ocular adverse events observed with licaminlimab in the study. Drop comfort was also evaluated and was similar to artificial tears.

According to Eric Donnenfeld, MD, a clinical professor of Ophthalmology at New York University and Chair of Oculis’ Cornea Scientific Advisory Board, licaminlimab could be an option for patients diagnosed with DED.

“The precision medicine approach with licaminlimab could be a groundbreaking paradigm shift in ophthalmology and the treatment of DED. 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,” Donnenfeld said in the news release. “To my knowledge, Licaminlimab is the first dry eye disease medication to demonstrate in a clinical trial a predictive treatment effect in patients with a common genetic biomarker to potentially solve this problem.”

Christophe Baudouin, MD, PhD, a professor of ophthalmology and chairman of Ophthalmology III at Quinze-vingts National Ophthalmology Hospital in Paris, and member of Oculis Scientific Advisory Board, also lauded the news.

“I am very excited to see that licaminlimab, with its dual anti-inflammatory and anti-apoptotic mechanism of action, targets the origin of DED and has the potential to be truly disease-modifying as shown by improvements in several clinical signs of DED, including corneal staining,” he said in the news release.

DED is estimated to impact nearly 40 million people in 2023 in the US alone.² It is known as a multifactorial disease in which ocular surface inflammation plays a central role in sustaining the pathological state.^3,4 It usually affects both eyes and patients may experience a stinging, burning, or scratchy sensation. In addition, some patients experience sensitivity to light, eye redness, difficulty wearing contact lenses, difficulty with nighttime driving, and blurred vision which can greatly affect their quality of life.

Of the approximately 20 million patients who are diagnosed with DED in the US, about half, or 10 million are considered to have moderate to severe disease; however, only 9% receive prescription treatment, primarily with anti-inflammatory medications.² Despite currently available treatments, only 13% of chronic patients said that they experienced lasting relief⁵ highlighting the tremendous unmet need remaining in this underserved patient population. Furthermore, given the heterogenicity of the DED patient population, there is a need for more personalized treatment approaches, to improve outcomes for patients.

References:

1. AG OH. 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. GlobeNewswire News Room. Published June 10, 2024. Accessed June 10, 2024. https://www.globenewswire.com/news-release/2024/06/10/2895804/0/en/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-Strat.html

2. DRG (part of Clarivate) – Dry Eye Disease Landscape and Forecast report 2020

3. TFOS DEWS II The Ocular Surface 15 (2017)
   Baudouin C. Dry Eye Disease, the complex interactions of vicious cycles.

4. EuDES European Dry Eye Society
   https://www.dryeye-society.com/resources/dry-eye-disease-complex-interactions-vicious-cycles

5. Mukamal, R. Why is Dry Eye So Difficult to Treat? 2021 https://www.aao.org/eye-health/tips-prevention/fix-dry-eye-treatment-eyedrops