Palatin Phase 3 results

March 1, 2024

This is not investment advice. We used AI and automated software tools for most of this research. A human formatted the charts based on data / analysis from the software, prompted the AI to do some editing, and did some light manual editing. We did some fact checking but cannot guarantee the accuracy of everything in the article. We do not have a position in or a relationship with the company.

Phase 3 results

Palatin Technologies announced the results of the PL9643 MELODY-1 pivotal Phase 3 clinical trial. Here is a detailed summary of the study and its outcomes:

• Study Background
  • Objective: The MELODY-1 trial aimed to evaluate the safety and efficacy of PL9643, a melanocortin receptor agonist, versus a vehicle (placebo) in the treatment of dry eye disease (DED).
  • Design: This was a multi-center, randomized, double-masked, and vehicle-controlled study.
  • Duration: Treatment lasted for 12 weeks, preceded by a 4-week run-in period.
  • Population: The trial enrolled 575 patients with moderate-to-severe DED at various sites in the U.S. The demographic analysis showed that 60% of the subjects were over the age of 60, and 68% were female.
• Efficacy Results
  • Co-Primary Endpoints: The study had two co-primary endpoints: a symptom endpoint (pain) and a sign endpoint (conjunctival lissamine green staining).
  • Symptom Endpoint Success: After adjusting for age and gender in the Intent-to-Treat (ITT) analysis, PL9643 demonstrated clinically meaningful and statistically significant improvements in the co-primary symptom endpoint of pain (p<0.025) and multiple other symptom endpoints.
  • Sign Endpoint Analysis: While PL9643 showed positive treatment effects over vehicle for the co-primary sign endpoint and secondary sign endpoints in the ITT population, these did not achieve statistical significance.
  • Vehicle Response: The study noted a high vehicle response, yet PL9643 treatment was still found to be clinically meaningful and statistically significant in reducing patient symptoms for the co-primary pain endpoint and other symptom endpoints.
• Safety and Tolerability
  • Overall Safety: PL9643 was well-tolerated with fewer ocular treatment-related adverse events compared to the vehicle (5.6% in PL9643 arm vs. 6.3% in vehicle arm).
  • Discontinuations: There were fewer study discontinuations in the PL9643 arm (7.0%) compared to the vehicle arm (11.1%).
• Company Statements
  • Palatin Technologies' Perspective: The company highlighted the rarity of a single DED clinical study showing efficacy for both a sign and a symptom. They are encouraged by PL9643's potential to address both aspects of DED.
  • Future Plans: Palatin intends to complete a comprehensive data analysis, meet with the FDA to discuss the next pivotal Phase 3 clinical trial design, and seek a collaboration partner for the DED program.

The company's interpretation of the PL9643 MELODY-1 trial results warrants a critical analysis, especially considering the potential biases and the implications of post hoc analyses.

• Dangers of Post Hoc Analyses
  • Data Dredging: Post hoc analyses, especially those not predefined in the study protocol, can lead to data dredging where results are found by chance rather than reflecting true efficacy. This risks overinterpreting findings that may not be replicable in subsequent studies.
  • Bias Introduction: Adjusting analyses after the fact introduces the possibility of bias, as the adjustments are made with knowledge of the initial outcomes. While such adjustments can be legitimate and necessary for understanding the data fully, they must be approached with caution and transparency.
  • Regulatory Skepticism: Regulatory bodies like the FDA are cautious about post hoc analyses precisely because of these risks. Such analyses are generally considered less robust than pre-specified analyses, and reliance on them can complicate regulatory approval processes.
• Critical Perspective on Company's Interpretation

  While the company's interpretation aims to highlight the potential of PL9643 as a DED treatment, it's crucial to differentiate between statistically significant outcomes that were part of the original study design and those that emerged from post hoc analyses. The distinction is important for a few reasons:

  • Scientific Rigor: True scientific rigor demands pre-specified endpoints and analyses plans to prevent the introduction of bias and ensure that the study results are robust and replicable.
  • Clinical Relevance: The clinical relevance of findings from post hoc analyses can be questioned, especially if they deviate significantly from the primary study outcomes. Regulators and clinicians look for consistent evidence of efficacy and safety across a range of measures.
  • Transparency and Trust: While adjusting for known DED risk factors like age and sex is scientifically valid, the rationale and methods for these adjustments should be transparently reported to maintain trust among regulators, investors, and the scientific community.