Palatin Technologies has announced breakthrough results from updated analyses of its Phase 3 MELODY-1 clinical trial, revealing that its investigational drug PL9643 achieved complete symptom resolution in patients with dry eye disease (DED) – an outcome no currently approved therapy has demonstrated.
The responder analyses showed that a significantly higher percentage of patients treated with PL9643 achieved complete symptom resolution compared to placebo across six of 13 symptom endpoints (p<0.05) at the 12-week treatment mark. This level of symptom clearing represents a potential paradigm shift in DED treatment.
"Achieving statistically significant symptom resolution across multiple endpoints, a first among dry eye therapies, is a major breakthrough that could transform treatment," said Carl Spana, Ph.D., President and CEO of Palatin Technologies. "These results reinforce PL9643's potential as a best-in-class therapy with a differentiated mechanism of action."
Unprecedented Efficacy Profile
The updated analyses evaluated the percentage of patients achieving complete symptom clearing across 13 pre-specified symptom endpoints. Additionally, researchers utilized a Symptom Composite Score based on seven Visual Analog Scale (VAS) symptom ratings to quantify overall symptom burden.
Key findings demonstrated that PL9643-treated patients experienced:
- Statistically significant symptom resolution as early as two weeks
- Continued improvement through 12 weeks with no signs of plateau
- Complete symptom resolution at higher rates than placebo across all 13 symptom endpoints
In contrast, patients receiving placebo showed minimal improvement that quickly plateaued. The symptom clearing pattern with PL9643 aligns with the resolution of inflammation, consistent with the mechanism of action of melanocortin agonists.
Michael Raizman, M.D., Chief Medical Officer of Palatin Technologies, emphasized the significance of these results: "Demonstrating statistically significant improvement in the Symptom Composite Score — especially as early as week 2 and sustained through week 12 — strongly signals meaningful patient benefit."
Regulatory Pathway and Market Potential
The findings hold particular regulatory relevance as they align with FDA approval guidance for dry eye drug development (2020), which supports the use of responder analyses to demonstrate symptom improvement. The guidance specifically requires a statistically significant difference in the proportion of patients achieving complete symptom resolution – a criterion PL9643 has now met.
Dry eye disease represents a substantial market opportunity, affecting an estimated 38 million Americans. However, only about 18 million are diagnosed, and less than 10% of those diagnosed receive prescription treatment. The global dry eye disease market is projected to grow from $6.11 billion in 2024 to $7.46 billion by 2029, with a CAGR of 4.09%.
"No currently approved DED treatment offers PL9643's exceptional safety and tolerability profile, rapid onset of efficacy, and statistically significant results across multiple symptom and sign endpoints," Dr. Spana noted. "These findings position PL9643 as a compelling, potentially best-in-class treatment for dry eye disease."
Novel Mechanism of Action
PL9643 is a melanocortin receptor agonist, representing a novel approach to treating dry eye disease. The melanocortin receptor system influences inflammation, immune responses, and other physiological functions. By modulating these receptors, PL9643 activates natural pathways to resolve inflammation in the eye.
This mechanism differs from existing therapies, which many physicians and patients consider inadequate and often require months to demonstrate activity. PL9643's rapid onset of action – showing significant effects by week 2 – could provide a substantial advantage in the treatment landscape.
Clinical Development Plan
Palatin successfully completed the MELODY-1 Phase 3 trial last year, with 575 patients enrolled across U.S. sites. The co-primary symptom endpoint of pain met statistical significance (P<0.025), and seven secondary symptom endpoints achieved statistical significance (P<0.05) at the 12-week treatment period.
The remaining Phase 3 clinical program consists of two additional studies, MELODY-2 and MELODY-3, each evaluating both sign and symptom endpoints. Subject to securing collaboration and funding, patient enrollment could begin in the second half of this year, with topline data expected in the second half of next year.
Addressing an Unmet Medical Need
Dry eye disease is a common inflammatory condition that, if left untreated, can cause extreme pain and permanent damage to the cornea and vision. The disease affects the cornea and conjunctiva, resulting in irritation, redness, pain, and blurred vision.
Characterized by insufficient moisture and lubrication on the eye's surface, DED leads to dryness, inflammation, discomfort, diminished quality of life, and in severe cases, permanent vision impairment. Current therapies are generally considered inadequate by many healthcare providers and patients.
With its promising efficacy profile and excellent safety and tolerability data, PL9643 represents a potential breakthrough in addressing this significant unmet medical need. Palatin is actively progressing discussions with potential collaboration partners and aims to finalize a deal in the second half of this year.
