Results from the KOMFORT phase II trial of oral difelikefalin for the treatment of pruritus in notalgia paresthetica is published in the New England Journal of Medicine

The manuscript, titled “Phase II 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.

“Notalgia paresthetica is an under-recognized neuropathic itch disorder characterized by pruritus of the upper back for which there is no approved treatment,” said Brian Kim, M.D., MTR, lead author of the paper and Vice Chair of Research for the Kimberly and Eric J. Waldman Department of Dermatology, Icahn School of Medicine at Mount Sinai, NY. “In the KOMFORT Phase II trial, oral difelikefalin demonstrated encouraging potential to address the significant unmet need for an effective treatment option for this burdensome condition. I look forward to the continued evaluation of oral difelikefalin in a clinical trial program for the treatment of pruritus in patients with notalgia paresthetica.”

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

KOMFORT Phase II Trial Results: As previously announced and presented at the 31st European Academy of Dermatology and Venereology (EADV) Congress, the KOMFORT Phase II 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 greater than 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.

See-ORIGINAL ARTICLE.VOL. 388 NO. 6, FEB 09, 2023."Phase II Trial of Difelikefalin in Notalgia Paresthetica";B.S. Kim and Others.N Engl J Med 2023; 388:511-517.