Breakthrough Clinical Results
OKYO Pharma announced positive top-line data from its Phase 2 trial of urcosimod for treating neuropathic corneal pain (NCP). The 18-patient trial showed a significant reduction in pain scores in patients with moderate to severe NCP, even those who had not responded to prior treatments. 75% of patients receiving 0.05% urcosimod achieved greater than 80% pain reduction. No serious adverse events were reported. OKYO plans to meet with the FDA to discuss next steps for urcosimod, which has already received Fast Track designation.
Key Highlights
- 75% of patients receiving 0.05% urcosimod achieved >80% pain reduction.
- Statistically significant reduction in mean pain scores (p-value = 0.025).
- No serious adverse events reported.
- Urcosimod showed early efficacy as early as Week 4.
Study Design Parameters
Study Design Parameters and Endpoints in Neuropathic Corneal Pain Trials
Study Designs
- Preclinical models include photobiomodulation (PBM) studies in Thy1-YFP mice across four models (normal control, sham control, pulled nerve, full transection)
- Corneal injury models in Wistar rats comparing topical applications of normal saline, oxybuprocaine, and N-propylamiodarone bromide (NPA)
- Intact cornea studies evaluating responses to oxybuprocaine, capsaicin, and NPA
- Electrophysiological recordings of mouse ciliary nerve activity measuring responses to various stimulations
- Cross-sectional clinical studies comparing patients with short tear film break-up time dry eye (n=60) to healthy volunteers (n=46)
- Questionnaire-based assessments administered to 228 consecutive subjects
Assessment Methods
- Von Frey test (VFT) for mechanical sensitivity
- Eye-wiping test (EWT) for chemical sensitivity
- Cochet-Bonnet corneal esthesiometer for tactile and pain sensations
- In Vivo Confocal Microscopy (IVCM) for corneal morphology and nerve structures
- Electrically elicited corneal reflex measurements
- Extracellular activity recording of ciliary nerve
Validated Questionnaires
- Self-Administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS)
- Pain Detect (PD) questionnaires
- Ocular Comfort Index (OCI) - highest rated for psychometric properties
- Contact Lens Discomfort Index (CLDI)
Key Endpoints
- Duration of analgesic effect (e.g., 215±11 min for NPA vs 25±2 min for oxybuprocaine)
- Corneal pain threshold and tactile sensation measurements
- Spontaneous and evoked activity of the ciliary nerve
- Latency, amplitude and duration of corneal reflex
- Correlation between subjective pain scores and objective measurements
- Quality of life (QoL) assessments
- Mental health conditions including PTSD and depression
- Wound healing and nerve morphology assessments
Recent Innovative Approaches
- Proxymetacaine Hydrochloride 2% instillation to differentiate dry eye disease from ocular neuropathic pain
- Deep-learning analysis of IVCM images measuring nerve area density, thickness, tortuosity, junction points, neuromas, and immune cell density
- Aprepitant formulations tested for ocular toxicity and analgesic/anti-inflammatory efficacy in corneal alkali burn models
- Multifactorial pain scale used in equine studies to evaluate ocular pain treatments
Patient Classification Parameters
- Chronic ocular pain defined as duration >1 month
- Corneal hyperalgesia defined as pain sensitivity ≥40 mm
- Central NCP identified by lack of signs justifying pain and non-response to topical anesthesia
These diverse study designs and endpoints reflect the multifaceted approach required to investigate the complex pathophysiology and treatment options for neuropathic corneal pain.
Recent Studies
Recent Studies on Neuropathic Corneal Pain
Nortriptyline Study (2021)
- Intervention: Oral nortriptyline for patients with neuropathic corneal pain (NCP)
- Efficacy: Mean ocular pain improved from 5.7 ± 2.1 to 3.6 ± 2.1 after 10.5 months (p < 0.0001)
- 40% of patients had ≥50% improvement, 20% had 30-49% improvement
- Quality of life improved from 6.0 ± 2.5 to 4.3 ± 2.4 (p = 0.019)
- Safety: 26.6% discontinued treatment due to persistent side effects
- Conclusion: Effective in relieving NCP symptoms in patients with centralized component who tolerated the drug
Photobiomodulation Study (2025)
- Intervention: Photobiomodulation (PBM) therapy in preclinical mouse models
- Efficacy: Significantly reduced behavioral manifestations of pain in both pulled nerve and full transection models
- In pulled nerve model: von Frey test improved from D1 = 0.050 ± 0.008 to D56 = 0.09 ± 0.014 (P = 0.02)
- In full transection model: von Frey test improved from D1 = 0.024 ± 0.0028 to D56 = 0.073 ± 0.0094 (P = 0.02)
- Conclusion: Promising nonpharmacologic intervention for NCP with early intervention potentially crucial
Cannabinoids Study (2020)
- Intervention: Topical Δ-tetrahydrocannabinol (ΔTHC), cannabidiol (CBD), and HU-308 (CBD derivative)
- Efficacy: All three cannabinoids reduced pain score and neutrophil infiltration in wild-type mice
- Mechanism: ΔTHC effects mediated via CBR; CBD effects via 5-HT receptors; HU-308 effects via CBRs
- Conclusion: Cannabinoids could be a novel clinical therapy for corneal pain and inflammation
Pregabalin Study (2022)
- Intervention: Continuous treatment with pregabalin in a rat dry eye model
- Efficacy: Effectively ameliorated hypersensitivity and hyperalgesia
- Normalized neural activity and α2δ-1 subunit upregulation
- Finding: Effective even after chronic pain had been established
Mirogabalin Study (2023)
- Intervention: Mirogabalin (10 or 3 mg/kg) in a rat dry eye disease model
- Mechanism: Novel ligand for the α2δ subunit of voltage-gated calcium channels
- Efficacy: Significantly suppressed capsaicin-induced eye-wiping behavior
- 10 mg/kg dose significantly reduced c-Fos expression in the trigeminal nucleus
- Finding: Suppressed DED-induced hyperalgesia and chronic ocular pain
Urcosimod Clinical Trials Beyond Neuropathic Corneal Pain
Based on a comprehensive review of available information, there is insufficient data to determine what other indications Urcosimod is being trialed for beyond neuropathic corneal pain.
The current clinical development program for Urcosimod (also known as MK-2884) appears to be focused primarily on its application for neuropathic corneal pain, which leverages its properties as a TRPM8 agonist. However, specific details about:
- Additional clinical indications
- Intervention models for other conditions
- Dosing regimens for alternative applications
- Study designs for trials beyond ocular applications
- Phase II or Phase III trials for non-ocular conditions
are not currently available in the reviewed information.
As a TRPM8 agonist, Urcosimod has theoretical potential for application in various pain and neurological conditions, but confirmed clinical trials for indications beyond neuropathic corneal pain cannot be verified at this time.
For patients and healthcare providers interested in the clinical development of Urcosimod, monitoring official clinical trial registries and pharmaceutical announcements would be recommended to stay informed about any expansion of its investigational uses.