Palatin Therapeutics, Inc. released data from the MELODY-1 pivotal phase 3 clinical trial assessing the safety and efficacy of PL9643, its dry eye disease (DED) candidate.
Let’s start with Palatin.
Based in Cranbury, New Jersey, the biopharmaceutical company’s focus lies in developing first-in-class medicines based on molecules that regulate melanocortin peptide receptor system activity (I’ll explain that science below).
Its therapeutic pipeline for inflammation and autoimmune conditions includes ocular candidates for:
- DED (phase 3)
- Retinal disease (preclinical stage)
See here for the complete list of candidates and diseases.
To date, the company’s first FDA-approved commercial product is Vyleesi (bremelanotide injection), the first melanocortin-based treatment for premenopausal women suffering from hypoactive sexual desire disorder (HSDD).
Explain this science.
The melanocortin receptor (MCr) system—consisting of five MCrs: MCR1 to MCR5—plays a role in impacting inflammation, immune system responses, metabolism, food intake, and sexual function, according to Palatin.
Regulation of these receptors are known to have “medically significant pharmacological effects,” the company stated.
How it works: Palatin’s therapeutics are intended to activate endogenous melanocortin pathways to undue damaging inflammation and enable time for affected tissues to heal.
And the ocular connection?
As tissues and immune cells within the eye are also known to express MCrs, Palatin’s MCr system-based molecules have been developed to “directly activate natural pathways to resolve disease-associated inflammation.”
Such MCrs are “a highly tractable target for melanocortin agonists to provide relief and healing for those living with ocular diseases.
Gotcha. Now give me some clinical background on PL9643.
Formulated as a topical treatment, PL9643—Palatin’s most advanced ocular product— PL9643 previously demonstrated statistically significant improvement in multiple signs and symptoms among moderate-to-severe DED patients, as well as excellent ocular tolerability.
This phase 2 study data (NCT04268069)—announced in December 2020—also revealed that the study’s primary endpoints did not reach statistical significance in the overall enrolled patient population (measured at 12 weeks).
Which leads us to this phase 3 trial.
PL9643 was evaluated in the multicenter, double-masked, randomized, vehicle-controlled phase 3 MELODY-1 trial (NCT05201170).
The study enrolled 570 dry eye patients (aged 18+; 60% <60; 68% female) who initially underwent a 14-day study run-in period, in which they received a vehicle ophthalmic solution bilaterally, three times a day (TID).
And then?
Following this time period, participants were randomized 1:1 to receive one of two doses, bilaterally and TID:
- PL9643 ophthalmic solution
- n = 288
- Vehicle ophthalmic solution
- n =287
Treatment period: 12 weeks.
Important note: The final participant enrollment total clocked in at 575 (five more patients than the originally reported 570).
Now the important question: What were the primary endpoints?
Three outcome measures included:
- Inferior corneal fluorescein staining
- Measured: baseline to Week 12
- Ocular discomfort
- Measured: baseline through Week 2
- Conjunctival sum lissamine green staining
- Measured: Baseline and Week 12
And the findings?
First, investigators adjusted the study’s intent-to-treat (ITT) analysis,—which is used in randomized trials where all participants assigned to one of the two treatments are analyzed together—for age and gender.
After adjustment, Palatin reported that PL9643 was well-tolerated and “demonstrated clinically meaningful (visual analog score reduction of > 10 points from baseline)” as well as statistically significant data for ocular pain (p < 0.025) (co-primary endpoint) and other system endpoints.
So that’s the good news … now give me the bad.
While PL9643 for both ocular pain and secondary endpoints demonstrated “positive treatment effects over vehicle in the ITT population,” it did not reach statistical significance.
Further, in the unadjusted planned analyses, all endpoints also failed to achieve statistical significance.
Any adverse events?
The company reported that fewer ocular treatment-related adverse events (AEs) occurred in the PL9643 arm (5.6%) than vehicle (6.3%).
And for study discontinuations: fewer occurred in the PL9643 arm (7%) vs vehicle (11.1%).
What did the company have to say about this data?
Palatin President and CEO Carl Spana, PhD, noted that, “it is rare for one clinical study in DED to show efficacy for both a sign and symptom.”
He added that the company’s comprehensive data analysis is ongoing; once completed, “we plan to meet with the FDA to discuss and get feedback on the design of the next pivotal phase 3 clinical trial.”
And …
Palatin plans to continue its ongoing efforts for a collaboration partner to further progress its DED program, according to Spana.