Results of Phase III Trial Show Promise of Potential First-in-Class Treatment for Dry Eye Disease

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A novel therapy for dry eye disease (DED) achieved clinically meaningful and statistically significant results in the pivotal Phase III MELODY-1 clinical trial.¹ PL9643 ophthalmic solution, developed by Palatin Technologies, Inc., is a melanocortin agonist with a novel mechanism of action that, if approved, would be a first-in-class therapy for DED.²

"Even with a high vehicle response, PL9643 treatment was clinically meaningful and statistically significantly effective on an [intent-to-treat (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 press release. "We are pleased that PL9643 treatment demonstrated excellent safety and tolerability data, including superior efficacy results compared to vehicle across multiple sign endpoints."¹

DED is a chronic, multifactorial condition of the ocular surface, which is characterized by hyperosmolarity, inadequate production and instability of tear film, and damage and inflammation of the ocular surface. An estimated 16.4 million US adults have been diagnosed with DED, which can have a significantly negative impact on quality of life, causing ocular discomfort, fatigue, and visual disturbance.^3,4

The development of DED is frequently linked to aging, with women twice as likely to develop DED as men. The condition commonly manifests during pregnancy, menopause, and postmenopause.

The multi-center, randomized, double–masked, vehicle–controlled MELODY-1 trial analyzed the safety and efficacy of PL9643 in patients with moderate-to-severe DED. The study design was based on positive findings from a Phase II trial and an end-of-phase meeting with the FDA that discussed key elements of the clinical program.⁵

The MELODY-1 trial’s co-primary efficacy endpoints were the clinical symptom of pain and the clinical sign of conjunctival lissamine green staining, in addition to other symptom and sign secondary endpoints. PL9643 was administered over 12 weeks with a four-week run-in period in 575 patients who were randomly assigned to receive the study drug or vehicle.

After adjusting the ITT data to account for both age and sex in the primary statistical analysis, the drug produced clinically meaningful and statistically significant outcomes for the co-primary symptom endpoint of pain, with a visual analog score reduction of >10 points from baseline, (p<0.025) and multiple other symptom endpoints. For the co-primary sign and secondary sign endpoints, PL9643 produced positive effects compared with vehicle in the ITT population but did not reach statistical significance, nor did it achieve statistical significance for the co-primary endpoints and secondary endpoints in the unadjusted planned analyses.¹

In terms of safety, PL9643 was well-tolerated, with fewer treatment-related adverse effects in those administered PL9643 (5.6%, N=16/288) compared with vehicle (6.3%, N=18/287), and fewer study discontinuations (7.0%, N=20/288) compared with vehicle (11.1%, N=32/287).

"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," Spana said in the release. "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 III clinical trial. Furthermore, we will continue with our efforts for a collaboration partner for our DED program."¹

References

1. Palatin Announces Results of PL9643 MELODY-1 Pivotal Phase 3 Clinical Trial in Patients with Dry Eye Disease (DED). Palatin Technologies. News release. February 28, 2024. Accessed February 28, 2024. https://prnmedia.prnewswire.com/news-releases/palatin-announces-results-of-pl9643-melody-1-pivotal-phase-3-clinical-trial-in-patients-with-dry-eye-disease-ded-302073599.html

2. Palatin Announces Database Lock for Pl9643 Melody-1 Pivotal Phase 3 Clinical Trial in Patients With Dry Eye Disease (DED). Palatin Technologies. News release. February 5, 2024. Accessed February 28, 2024. https://palatin.com/press_releases/palatin-announces-database-lock-for-pl9643-melody-1-pivotal-phase-3-clinical-trial-in-patients-with-dry-eye-disease-ded/

3. Dry eye. National Institutes of Health. Updated April 8, 2022. Accessed February 28, 2024. https://www.nei.nih.gov/learn-about-eye-health/eye-conditions-and-diseases/dry-eye

4. Labetoulle M, Benitez del Castillo JM, Barabino S, et al. Artificial tears: biological role of their ingredients in the management of dry eye disease. Int J Mol Sci. 2022;23(5):2434. doi:10.3390/ ijms23052434

5. Palatin Completes Enrollment in Phase 3 Melody-1 Study of Pl9643 for the Treatment of Patients With Dry Eye Disease. Palatin Technologies. News release. September 7, 2023. Accessed February 28, 2024. https://palatin.com/press_releases/palatin-completes-enrollment-in-phase-3-melody-1-study-of-pl9643-for-the-treatment-of-patients-with-dry-eye-disease/