Alcon, Inc. released positive topline results from two pivotal phase 3 clinical trials—COMET-2 and COMET-3—evaluating the safety and efficacy of AR-15512 for the treatment of the signs and symptoms of dry eye disease (DED).
Refresh me on AR-15512.
Originally developed by Aerie Pharmaceuticals, which Alcon acquired in November 2022, the first-in-class investigational product candidate is a topical transient receptor potential melastatin 8 agonist (TRPM8 for short).
For context: TRPM8 is a cold-sensing receptor located in the cornea and eyelid that has the potential to relieve symptoms of DED.
And to note: AR-15512 is formulated to be administered via topical ocular instillation.
And now these COMET trials.
Before we get to the phase 3 trials, let’s discuss COMET-1: a multicenter, vehicle-controlled, double-masked, randomized phase 2b study (NCT04498182).
Completed in 2021, the trial evaluated DED participants dosed with 0.003% (high dose) or 0.0014% (low dose) AR-15512 or vehicle, twice daily (BID), for 12 weeks.
The result: While the study’s predefined co-primary study endpoints failed, “AR-15512 demonstrated statistically significant improvements in DED signs, symptoms, and disease-related [quality of life].”
See here for the full study and result details, published in 2022.
Gotcha. Moving on to the phase 3 trials.
The COMET-2 (NCT05285644) and COMET-3 (NCT05360966) were multicenter, vehicle-controlled, double-masked, randomized studies that evaluated AR-15512 0.003% vs vehicle when administered once a day in both eyes for 90 days in the following participants:
- COMET-2 = 465 patients (aged 30+)
- COMET-3 = 467 patients (aged 30+)
What was measured?
Primary outcomes for both trials included an unanesthetized Schirmer test (at Day 14), as measured by the number of participants with ≥ 10 mm increase in unanesthetized Schirmer score.
See here and here for the nine secondary outcomes. Note: all outcomes were the same for both trials.
And the findings?
Per Alcon, both trials achieved their primary endpoint (p <0.0001).
For secondary endpoints, the company reported the data “demonstrated the rapid onset and sustained tear production associated with AR-15512 compared to vehicle, as early as Day 1 and persistent to Day 90.”
Further, AR-15512 was found to be well tolerated with no serious ocular adverse events.
Significance?
Edward Holland, MD, a key advisor on both COMET trials and senior scientific advisor at Alcon, noted “the rapid speed of onset” as a major gap among current dry eye medications.
“AR-15512 demonstrated this important achievement in both pivotal efficacy and safety studies and it represents a first-in-class candidate for chronic dry eye,” he stated.
So what’s next?
Alcon expects to file a new drug application (NDA) for AR-15512 with the FDA by mid-2024 … so stay tuned for updates on this front!