FDA gives IND clearance to OKYO Pharma for OK-101 in neuropathic corneal pain

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OKYO Pharma Ltd announced the FDA has cleared OK-101 as its first Investigational New Drug (IND) application for the treatment of NCP.

According to a news release,¹ the initial IND submission to FDA proposed an open-label design for the clinical trial. Based on positive feedback from FDA, the Phase 2 study is now designed as a double-masked, randomized, 12-week placebo-controlled trial comparing OK-101 to placebo in NCP patients.

NCP is a condition that causes pain and sensitivity of the eyes, face, or head. The exact cause of NCP is unknown but thought to result from nerve damage to the cornea with inflammation. It can exhibit as a severe, chronic, or debilitating condition in patients suffering from a host of ophthalmic conditions, is presently treated by various topical and systemic treatments in an off-label fashion. There are no approved commercial treatments currently available for this condition.¹

According to the company, OK-101 is a lipid conjugated chemerin peptide agonist of the ChemR23 G-protein coupled receptor which is typically found on immune cells of the eye responsible for the inflammatory response. OK-101 was developed using a membrane-anchored-peptide technology to produce a novel long-acting drug candidate for treating dry eye disease.²

Moreover, the company noted that OK-101 has been shown to produce anti-inflammatory and pain-reducing activities in mouse models of dry eye disease and corneal neuropathic pain (NCP), respectively, and is designed to combat washout through the inclusion of the lipid anchor built into the drug molecule to enhance the residence time of OK-101 within the ocular environment. OK-101 recently showed clear statistical significance in multiple endpoints in a recently completed Phase 2, multi-center, double-blind, placebo-controlled trial of OK-101 to treat DED.

A total of 54 patients are planned for the study, with NCP disease confirmed via confocal microscopy. The primary endpoint will be measured utilizing VAS pain relief scores. These protocol changes will enable a statistically valid demonstration of a true drug effect of OK-101 on NCP symptoms. OKYO Pharma is scheduling this trial to begin in Q2 2024.

The OK-101 trial, designed as a single-center trial, will be led by Pedram Hamrah, MD, of Tufts Medical Center, as principal investigator. Hamrah is a professor and vice chair of Research and Academic Programs, co-director of the Cornea Service and Director of the Center for Translational Ocular Immunology at Tufts Medical Center. An ophthalmologist and a clinician-scientist, Hamrah is a leading expert in NCP and co-inventor on the OK-101 patent. He is also a member of OKYO’s Scientific Advisory Board.

“I am very pleased that we have gained FDA IND clearance for the first drug to be tested for NCP, a debilitating disease,” Hamrah said in the news release. “Receiving the IND clearance in an important and novel indication was not a trivial hurdle to overcome. Now that the path has been opened for drugs to be tested in NCP, I am looking forward to working with the OKYO team to launch this important trial.”

Gary S. Jacob, PhD, CEO of OKYO, said the company is pleased to gain IND clearance for OK-101 to treat NCP as a second important disease target for the company.

“OK-101 recently demonstrated favorable tolerability in a Phase 2 trial of dry eye patients along with statistically significant improvements in dry eye symptoms such as stinging/burning and blurred vision, which are also hallmarks of NCP,” he said in the news release. “OK-101 was also shown in a cutting-edge mouse model of NCP to significantly reduce ocular neuropathic pain. We are looking forward to advancing OK-101 to potentially treat NCP, a chronically painful ocular disease with no FDA-approved therapy and a major unmet medical need for patients suffering from this condition.”

Earlier this year, OKYO Pharma announced the first-in-human, randomized, double-masked, placebo-controlled trial of OK-101 “established a clear and informed path for further development in Phase 3 registration trials.”²

The trial was conducted at 6 sites across the US and enrolled 240 subjects with DED dosed twice-daily. Patients were randomly divided into 3 cohorts, with one of the cohorts dosed with 0.05% OK-101 (n=80), a second with 0.1% OK-101 (n=80), and the third cohort with vehicle (n=80). Duration of treatment was 14 weeks with a 2-week run-in period on placebo.¹

Jay Pepose, MD, PhD, founder and medical director of Pepose Vision Institute and professor of Clinical Ophthalmology at Washington University School of Medicine in St Louis discussed the results in a statement from OKYO Pharma at the time.

“It is remarkable that in this first in human study of OK-101 ophthalmic solution, an analysis of all randomized subjects demonstrated a persistent, statistically significant improvement in multiple dry eye-related symptoms as early as day 15, along with a sign, total conjunctival lissamine green staining, by day 29,” he said. “Ameliorating this unique constellation of signs and symptoms may reflect the differentiated mechanism of action of OK-101. “

Pepose also noted that drop comfort was excellent and the safety profile favorable.

“This is evidenced by fewer subjects discontinuing study medication in the OK-101 arm (2.5%) than the placebo arm (3.8%) due to treatment-emergent adverse events,” he added. “This highly favorable tolerability profile is very significant because many patients commonly discontinue currently available dry eye medications due to unwanted side effects, such as blurred vision, conjunctival redness or altered taste sensation (dyseguesia).”

According to OKYO Pharma, the phase 2 results demonstrated superiority when compared to placebo in the sign endpoint of total conjunctival staining as measured by the Ora Calibra Staining Scale as early as Day 29 (p = 0.034). Furthermore, OK-101 demonstrated superiority when compared to placebo across at least two symptoms of DED including burning measured by the Ora Calibra 4-symptom questionnaire as well as burning/stinging measured by a visual analogue scale as early as Day 15 (p = 0.04 and p=0.03, respectively). A statistically significant improvement in blurred vision was also achieved at Day 29 (p = 0.01).²

Reference:

1. LTD OP. OKYO Pharma Receives FDA Approval of IND for OK-101 in Neuropathic Corneal Pain. GlobeNewswire News Room. Published February 9, 2024. Accessed February 9, 2024. https://www.globenewswire.com/news-release/2024/02/09/2826710/0/en/OKYO-Pharma-Receives-FDA-Approval-of-IND-for-OK-101-in-Neuropathic-Corneal-Pain.html

2. OKYO Pharma Announces OK-101 Successfully Achieved Statistical Significance for Both Sign and Symptom Endpoints in its First-in-Human Phase 2 Trial of OK-101 in Patients with Dry Eye Disease. Press release; January 8, 2024. Accessed January 8, 2024.
   https://www.globenewswire.com/news-release/2024/01/08/2805267/0/en/OKYO-Pharma-Announces-OK-101-Successfully-Achieved-Statistical-Significance-for-Both-Sign-and-Symptom-Endpoints-in-its-First-in-Human-Phase-2-Trial-of-OK-101-in-Patients-with-Dry-E.html