Orvida Pharma Reports Positive Phase 1a Safety Data for KM-023, First-in-Class TRPV3 Inhibitor for Olmsted Syndrome
核心洞察
Orvida Pharma (搜索) announced favorable safety results from Phase 1a testing of KM-023, a potential first-in-class oral TRPV3 (搜索) inhibitor for rare genetic skin diseases (搜索).
The Phase 1a study in 30 healthy volunteers showed no treatment-related adverse events in single-dose cohorts and only two mild, transient events in multiple-dose groups.
The company has initiated Phase 1b testing in Olmsted syndrome (搜索) patients, with the first patient dosed in a global study across the UK, US, and Europe.
Orvida Pharma (搜索) (formerly Kamari Pharma) has reported encouraging safety data from the Phase 1a portion of its clinical trial evaluating KM-023, a potential first-in-class oral TRPV3 (搜索) inhibitor for rare genetic skin diseases (搜索). The Israel-based biotechnology company has also initiated Phase 1b testing in patients with Olmsted syndrome (搜索), marking a significant milestone in developing the first targeted treatment for this devastating condition.
Favorable Safety Profile in Healthy Volunteers
The Phase 1a study was a randomized, placebo-controlled trial that evaluated the safety, tolerability, and pharmacokinetics of KM-023 in 30 healthy volunteers in France. The study design included both single-ascending dose (SAD) and multiple-ascending dose (MAD) cohorts to comprehensively assess the drug's safety profile.
In the SAD cohorts, 18 participants received at least one oral dose ranging from 15 mg to 50 mg across three dose levels, with no treatment-related adverse events (TRAEs) reported. The MAD cohorts involved 12 participants who received repeated twice-daily oral doses of 15 mg to 35 mg for up to five days. Only two mild, isolated TRAEs were observed in the MAD cohorts—one in the 15 mg twice-daily group and one in the 35 mg twice-daily group. Both adverse events were transient and did not require intervention, and no dose interruptions or discontinuations occurred due to adverse events.
The study also evaluated how KM-023 is absorbed and processed by the body, including drug levels in the blood and skin, and assessed the effect of food on the drug's pharmacokinetics.
Advancing to Patient Testing
Following the positive safety results, Orvida Pharma (搜索) has initiated the Phase 1b portion of the trial, which represents a global study evaluating KM-023 in patients with Olmsted syndrome (搜索) at clinical sites in the United Kingdom, the United States, and Europe. The first patient with Olmsted syndrome has been dosed in this Phase 1b study.
The Phase 1b study is designed to assess the safety, tolerability, pharmacokinetics, and exploratory signs of clinical activity of KM-023 in patients. Participants will receive KM-023 twice daily for 12 weeks, with regular clinical visits to monitor safety, drug exposure, and potential effects on disease symptoms. The trial will also evaluate drug levels in the blood and skin to better understand how KM-023 is distributed and acts in affected tissue.
The study is being conducted under protocols approved by the U.S. Food and Drug Administration (FDA), the U.K. Medicines and Healthcare products Regulatory Agency (MHRA), and the French Regulatory Agency (ANSM). Topline results are expected in the third quarter of 2026.
Addressing Critical Unmet Medical Need
Olmsted syndrome (搜索) is a rare and devastating genetic skin disorder that causes extremely painful, thickened skin on the palms and soles. The condition can severely limit mobility and everyday life, with no approved therapies currently available for patients.
"Olmsted syndrome (搜索) is a rare and devastating genetic skin disorder that causes extremely painful, thickened skin on the palms and soles. The condition can severely limit mobility and everyday life. With no approved therapies available today, patients face a profound unmet medical need," said Dr. David Aviezer, Chief Executive Officer of Orvida Pharma (搜索). "We believe KM-023 has the potential to become the first targeted treatment for this condition as well as for other rare genetic skin disorders, and we are committed to advancing its development with urgency for patients and families who need new options."
Scientific Rationale and Expert Perspective
KM-023 targets the TRPV3 (搜索) pathway, which plays a key role in the underlying disease biology of Olmsted syndrome (搜索). Prof. Edel O'Toole, MD, PhD, FRCP, of Queen Mary University of London, a leading dermatologist and investigator in the KM-023 Olmsted syndrome clinical program, emphasized the therapeutic potential of this approach.
"Olmsted syndrome (搜索) has profound effects on skin function and patient quality of life," said Prof. O'Toole. "TRPV3 (搜索) plays a key role in the underlying disease biology, and targeting this pathway with KM-023 represents a compelling therapeutic approach. These early safety data are encouraging and support the continued evaluation of KM-023 in patients with Olmsted syndrome."
Company Background
Orvida Pharma (搜索) is a clinical-stage biotechnology company developing first- and best-in-class treatments for rare and severe genetic skin diseases (搜索). The company's lead molecule, KM-023, is a novel, highly specific, and selective oral TRPV3 (搜索) inhibitor initially being developed for the treatment of Olmsted syndrome (搜索) and severe keratodermas (搜索). The company's management team comprises industry leaders with deep expertise in drug discovery, dermatological pharmaceutical development, and rare disease therapeutics.