KM-001, a novel TRPV3 inhibitor, demonstrates safety and preliminary efficacy in Phase 1b clinical study for the treatment of palmoplantar keratoderma

Abstract

Palmoplantar keratodermas (PPK) such as Pachyonychia Congenita (PC) and Punctate Palmoplantar Keratoderma type 1 (PPPK1) are rare genetic skin disorders, leading to hyperkeratosis of varying severity, pain in PC patients and disability with no approved specific therapy. TRPV3, a Ca2+ channel expressed in keratinocytes, is overexpressed in PPK patients. Our TRPV3 inhibitors demonstrate reduced hyperkeratosis and itch while normalizing epidermal differentiation and skin barrier in in vivo models. Phase 1b open label studies were conducted in UK and Israel in parallel, to assess the safety and efficacy of topical TRPV3 inhibitor, KM-001 1% cream. Eight patients in the UK (7 PC;1 PPPK1) and 7 patients in Israel (3 PC;4 PPPK1) completed the 12-week treatment period, with no drug-related SAEs and minimal TEAEs. Responder rate (defined as an improvement in at least one of the following parameters: CGI-S, IGA, PGI-S, PGI-C, VAS pain, PP-NRS itch) at the end of treatment was 86% (CI 48.7-97.4%) in Israel and 88% (CI 52.9-97.8%) in UK, and 47% of all the patients improved in at least 2 parameters, with a disease severity reduction trend. Six out of 10 PC patients reported a reduction in pain. KM-001 demonstrates potential as a novel therapy for PPK patients and further placebo-controlled clinical studies are planned.