Cara Therapeutics, Inc. announced theNew England Journal of Medicine (NEJM) has published results from the KOMFORT Phase 2 clinical trial of oral difelikefalin in patients with moderate-to-severe pruritus from notalgia paresthetica. The manuscript, titled “Phase 2 Trial of Difelikefalin in Notalgia Paresthetica,” includes data from 126 patients randomized to receive oral difelikefalin 2 mg or placebo twice daily for 8 weeks. The registrational Phase 2/3 program of oral difelikefalin will be enrolling notalgia paresthetica (NP) patients with moderate-to-severe pruritus.

The program will be comprised of an 8-week Phase 2 dose-finding portion followed by two identical Phase 3 studies. Following selection of the optimal dose based on the Phase 2 portion of the study, that dose will be evaluated for safety and efficacy in the Phase 3 portion. Further details about the program will be released during a Capital Markets Day on February 16, 2023.

KOMFORT Phase 2 Trial Results: As previously announced and presented at the 31stEuropean Academy of Dermatology and Venereology (EADV) Congress, the KOMFORT Phase 2 trial evaluating oral difelikefalin in patients with moderate-to-severe pruritus from notalgia paresthetica achieved the primary efficacy endpoint of change from baseline in the weekly mean of the daily 24-hour Worst Itch-Numeric Rating Scale (WI-NRS) score at Week 8 (-4.0 difelikefalin vs. -2.4 placebo, p=0.001). A significantly greater proportion of patients achieved a =4-point improvement in WI-NRS score at Week 8 with oral difelikefalin vs.

placebo (41% difelikefalin vs. 18% placebo, p=0.007). In addition, at Week 8, a significantly greater proportion of patients receiving oral difelikefalin vs.

placebo achieved a complete response (22% difelikefalin vs. 5% placebo, p<0.01). Secondary outcomes are reported in the NEJM manuscript and include itch-related quality-of-life and itch-related sleep measures.

Oral difelikefalin was generally well tolerated, with all adverse events in difelikefalin-treated patients reported as mild or moderate in severity. Headache, dizziness, constipation, and increased urine output were more commonly reported in patients on difelikefalin.