TRYPTYR (acoltremon)
trip’tir
Alcon Laboratories, Inc
Original Approval date: May 28, 2025

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DRUG TRIALS SNAPSHOT SUMMARY:

What is the drug for?

TRYPTYR is a TRPM8 thermoreceptor agonist that treats the signs and symptoms of dry eye disease (DED) in adults with history of DED.

How is this drug used?

TRYPTYR is available as an eye drop that is instilled one drop in each eye twice daily (approximately 12 hours apart).

Who participated in the clinical trials?

The FDA approved TRYPTYR based on evidence from two clinical trials (COMET-2 and COMET-3) of 931 patients with DED. The trials were conducted at 46 sites in the United States.

Two additional studies: COMET-1 and COMET-4 were included in the evaluation of safety benefit of TRYPTYR. The number of patients representing efficacy findings may differ from the number of patients representing safety findings due to different pools of study participants analyzed for efficacy and safety.

How were the trials designed?

The efficacy of TRYPTYR was evaluated in two clinical trials of 931 patients with DED.

Both COMET-2 and COMET-3 are Phase 3, multicenter, vehicle-controlled, double-masked, randomized studies whose primary endpoint was proportion of subjects with ≥10 mm increase from baseline in unanesthetized Schirmer Score on Day 14.

COMET-1 was a Phase 2b multicenter, vehicle-controlled, double-masked, randomized study conducted at 15 sites in the United States which randomized 369 subjects with a history of DED.

COMET-4 was a multicenter, vehicle-controlled, double-masked, randomized study conducted at approximately 10 sites in the United States which enrolled 275 subjects with a history of DED. 

Study COMET-2 and COMET-3 have a similar design. Each study is a multicenter, randomized, double-masked, vehicle-controlled Phase 3 study. The primary objective of these studies was to evaluate the safety and efficacy of TRYPTYR compared to vehicle. Subjects 30 years and older with a history of artificial tear use for DED were qualified based on signs and symptoms of DED at screening, and were requalified at Baseline (Day 1) following a 14-day vehicle run-in. COMET 2 enrolled 465 subjects at 23 study sites, whereas COMET-3 enrolled 466 subjects at 23 sites.

DEMOGRAPHICS SNAPSHOT

Figure 1 summarizes how many male and female participants were enrolled in the combined clinical trials used to evaluate the efficacy of TRYPTYR.

Figure 1. Baseline Demographics by Sex, Efficacy Population

_{Source: Adapted from FDA Review}

Figure 2 summarizes how many participants by race, were enrolled in the combined clinical trials used to evaluate the efficacy of TRYPTYR.

Figure 2. Baseline Demographics by Race, Efficacy Population

_{Source: Adapted from FDA Review}

Figure 3 summarizes how many participants by age were enrolled in the combined clinical trials used to evaluate the efficacy of TRYPTYR.

Figure 3. Baseline Demographics by Age, Efficacy Population

_{Source: Adapted from FDA Review}

Figure 4 summarizes how many participants by ethnicity were enrolled in the combined phase 3 clinical trials used to evaluate the efficacy of TRYPTYR.

Figure 4. Baseline Demographics by Ethnicity, Efficacy Population

_{Source: Adapted from FDA Review}

What are the benefits of this drug? 

TRYPTYR demonstrated a statistically significant increase in Schirmer tear score, improvement in tear production in two randomized, double-masked, vehicle-controlled multisite clinical studies (COMET-2 and COMET-3) in subjects with a diagnosis of dry eyes. The difference in the proportion of subjects who achieved ≥10 mm increase from baseline in unanesthetized Schirmer Score on Day 14 was 34.4% (95% CI: 26.9, 42.0) and 38.8% (95% CI: 30.8, 46.8) for COMET-2 and COMET-3, respectively.

Were there any differences in how well the drug worked in clinical trials among sex, race, and age? 

• Sex: TRYPTYR worked similarly in males and females.
• Race: TRYPTYR worked better in White and Black or African American patients as compared to Asian group. 
• Age: TRYPTYR worked better in patients aged 65 and older.

What are the possible side effects?

All serious events were assessed as not related to treatment, were generally nonocular in nature, and occurred at a higher incidence in the vehicle (22 subjects, 3.2%) group compared to either 0.0014% TRYPTYR (1 subject, 0.8%) or 0.003% TRYPTYR (12 subjects, 1.6%) groups in the integrated safety population.

The most common treatment-emergent adverse event experienced during the clinical studies was instillation site pain (burning or stinging) events: 49.7% in the TRYPTYR group and 4.1% in the vehicle group.

Were there any differences in side effects among sex, race, and age?

• Sex: The occurrence of side effects was similar in males and females.
• Race: The occurrence of side effects was similar across race subgroups.
• Age: The occurrence of side effects was similar in patients younger and older than 65 years of age.

GLOSSARY

CLINICAL TRIAL: Voluntary research studies conducted in people and designed to answer specific questions about the safety or effectiveness of drugs, vaccines, other therapies, or new ways of using existing treatments.

COMPARATOR: A previously available treatment or placebo used in clinical trials that is compared to the actual drug being tested.

EFFICACY: How well the drug achieves the desired response when it is taken as described in a controlled clinical setting, such as during a clinical trial.

PLACEBO: An inactive substance or “sugar pill” that looks the same as, and is given the same way as, an active drug or treatment being tested. The effects of the active drug or treatment are compared to the effects of the placebo.

SUBGROUP: A subset of the population studied in a clinical trial. Demographic subsets include sex, race, and age groups.

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