Palatin Technologies presented new data from the phase 3 MELODY-1 study at the 2025 Association for Research in Vision and Ophthalmology (ARVO) Annual Meeting. The updated responder analyses highlight PL9643's rapid onset of action, broad and statistically significant efficacy, and complete symptom resolution across multiple endpoints in patients with dry eye disease (DED), the company said in a press release. 

Palatin Technologies said the findings further strengthen PL9643's clinical profile and highlight its potential to address a critical unmet need.

The poster, titled "Efficacy and safety of PL9643 in participants with dry eye disease: results from a phase 3, randomized, vehicle-controlled study," was presented by George Ousler, MS, of Ora, Inc. The full poster is available at www.palatin.com.

Clinical Data Presented:

• PL9643 showed statistically significant symptom improvement at week 2, continuing through week 12.
• 6 of 13 symptom endpoints reached statistical significance for complete resolution.
• Symptom Composite Score (average of seven VAS metrics) improved significantly at week 2 and continued to improve through week 12.
• PL9643 improved ocular surface health, including total, inferior, and corneal staining.
• Safety data showed PL9643 was well tolerated, with a profile similar to or better than vehicle (vehicle similar to artificial tears).

"The consistency and strength of these data, including full symptom resolution in a significant portion of patients, underscore PL9643's potential to fill a major therapeutic gap," said Michael Raizman, MD, chief medical officer of Palatin, in the press release. "Combined with a robust safety profile, these results position PL9643 as a potential first-in-class DED treatment."

Regulatory Relevance
FDA 2020 approval guidance supports the use of responder analyses that demonstrates statistically significant increases in the proportion of patients achieving complete symptom resolution as a basis for approval. PL9643 meets this threshold across multiple endpoints, the company said in the press release. 

Phase 3 MELODY-1 PL9643 Design
Palatin successfully completed MELODY-1, its first phase 3 study, last year. The co-primary symptom endpoint of pain met statistical significance (P<0.025), and 7 secondary symptom endpoints met statistical significance (P<0.05), at the 12-week treatment period. The phase 3 MELODY-1 trial was a multi-center, randomized, double-masked and vehicle-controlled study that enrolled 575 patients at sites in the United States.

The trial evaluated the safety and efficacy of the melanocortin agonist, PL9643 ophthalmic solution after treatment for 12 weeks, compared to placebo in patients with moderate-to-severe DED, for multiple sign and symptom endpoints. Safety analysis from the phase 3 MELODY-1 trial indicated PL9643 was well-tolerated.

Next Steps in the Phase 3 PL9643 Program
The remaining phase 3 program includes 2 additional studies, MELODY-2 and MELODY-3, which will evaluate both signs and symptoms of DED. Pending partnership and funding, enrollment could begin in the second half of 2025, with topline data anticipated in the second half of 2026, the company said.