Palatin Updates Phase 3 PL9643 Data in Dry Eye Disease

Palatin Technologies has announced updated results from responder analyses of its pivotal Phase 3 Melody-1 clinical trial, which evaluated the safety and efficacy of PL9643 compared to placebo in the treatment of dry eye disease (DED).

The responder analysis focused on the percentage of patients achieving complete symptom resolution across 13 pre-specified symptom endpoints. Using the Symptom Composite Score—an average of individual Visual Analog Scale (VAS) ratings—Palatin measured the overall symptom burden from the patient’s perspective.

Statistically Significant Symptom Resolution Across Multiple Endpoints

Results demonstrated that at 12 weeks, a statistically significant greater percentage of patients receiving PL9643 achieved complete symptom resolution in 6 of the 13 symptom endpoints compared to placebo (p < 0.05). According to Palatin, this level of symptom resolution has not been previously achieved by any currently FDA-approved dry eye therapies.

Additionally, PL9643-treated patients showed statistically significant symptom resolution as early as 2 weeks, with improvements continuing through week 12 and no evidence of plateauing. An increasing number of symptoms achieved statistical significance from week 4 through week 12. In contrast, patients receiving placebo showed minimal improvement that plateaued quickly.

Across all 13 endpoints, a higher percentage of PL9643 patients reached complete symptom resolution than those treated with placebo.

CEO Highlights Differentiated Profile of PL9643

Carl Spana, PhD, President and CEO of Palatin Technologies, emphasized the clinical relevance of the findings in the company’s press release:

“These results reinforce PL9643's potential as a best-in-class therapy with a differentiated mechanism of action. Combined with its rapid, sustained efficacy and excellent safety and tolerability profile, PL9643 offers a compelling new option for patients.

Critically, these outcomes align with key FDA approval criteria for symptom improvement based on responder analyses. 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 — including a significantly higher percentage of patients achieving complete symptom resolution, which is a highly differentiating factor from currently approved therapies.”

Original Melody-1 Data and Clinical Program Outlook

Palatin originally announced results from the Melody-1 trial in early 2024. PL9643 treatment met the co-primary symptom endpoint of ocular pain (p < 0.025) and achieved clinically meaningful and statistically significant results across multiple additional symptom endpoints, though those were not specifically named.

While the co-primary sign endpoint and secondary sign endpoints showed positive treatment effects over vehicle in the Intent-to-Treat (ITT) population, they did not reach statistical significance.

Upcoming Phase 3 Trials: Melody-2 and Melody-3

Palatin confirmed its ongoing Phase 3 clinical program will continue with the Melody-2 and Melody-3 trials, each designed to evaluate both sign and symptom endpoints. The company anticipates that patient enrollment may begin in the second half of 2025, with topline data expected in the second half of 2026.