Palitin Misses Co-Primary Endpoints in Phase 3 Dry Eye Disease Trial

Palatin Technologies did not achieve statistical significance in the co-primary endpoints of its pivotal phase 3 clinical trial evaluating the safety and efficacy of PL9643 versus vehicle in the treatment of dry eye disease (DED).

MELODY-1 had two co-primary efficacy endpoints: one clinical symptom (pain) and one clinical sign (conjunctival lissamine green staining), as well as multiple other symptom and sign secondary endpoints of DED. Duration of treatment was 12 weeks with a 4-week run-in period. 

After adjusting the intent-to-treat (ITT) analysis for age and gender, PL9643 treatment demonstrated clinically meaningful (visual analog score reduction of >10 points from baseline) and statistically significant results for the co-primary symptom endpoint of pain (P<0.025) and multiple other symptom endpoints. PL9643 treatment for the co-primary sign endpoint and secondary sign endpoints demonstrated positive treatment effects over vehicle in the ITT population, but did not achieve statistical significance. In the unadjusted planned analyses, the co-primary endpoints and secondary endpoints did not reach statistical significance.

"Even with a high vehicle response, PL9643 treatment was clinically meaningful and statistically significantly effective on an ITT basis in reducing patient symptoms for the co-primary pain endpoint and multiple other symptom endpoints," Carl Spana, PhD, President and CEO of Palatin, said in a company news release. "We are pleased that PL9643 treatment demonstrated excellent safety and tolerability data, including superior efficacy results compared to vehicle across multiple sign endpoints."

"It is important to note that it is rare for one clinical study in DED to show efficacy for both a sign and a symptom. While additional analyses are ongoing, the initial results reinforce the potential of PL9643 as a treatment to address both symptoms and signs of DED," Dr. Spana said. "Our comprehensive data analysis is ongoing, and upon completion, we plan to meet with the FDA to discuss and get feedback on the design of the next pivotal phase 3 clinical trial. Furthermore, we will continue with our efforts for a collaboration partner for our DED program."

Safety analysis indicated PL9643 was well-tolerated. There were fewer ocular treatment related adverse events in the PL9643 arm (5.6%, n=16/288) compared to vehicle (6.3%, n=18/287), and fewer study discontinuations in the PL9643 arm (7.0%, n=20/288) compared to vehicle (11.1%, n=32/287).

The data from the pivotal Phase 3 MELODY-1 trial was a multicenter, randomized, double–masked and vehicle–controlled study that enrolled 575 patients at sites in the U.S. The trial evaluated the safety and efficacy of the melanocortin agonist, PL9643 ophthalmic solution, compared to vehicle in patients with moderate-to-severe DED, for multiple sign and symptom endpoints, after treatment for 12 weeks. The study design was based on positive phase 2 results of PL9643 for the treatment of DED, and an end-of-phase 2 meeting with the FDA on key elements of the pivotal Phase 3 clinical program.