Orvida Pharma Advances Hope for Rare, Painful Skin Disease

NESS ZIONA, Israel – April 15, 2026 – In a significant development for the rare disease community, Orvida Pharma has announced positive safety results from the first human study of its experimental drug, KM-023, and has begun testing it in patients with Olmsted syndrome, a devastating genetic skin disorder for which no approved therapy exists.

The clinical-stage biotechnology company, recently rebranded from Kamari Pharma, confirmed that the first patient has been dosed in a global Phase 1b study. This milestone follows a successful Phase 1a trial in healthy volunteers that established a favorable safety profile for the oral drug, a potential first-in-class TRPV3 inhibitor. The news provides a tangible beacon of hope for individuals suffering from a condition that causes extreme pain and severe disability.

“The favorable safety profile observed in Phase 1a represents an important milestone for KM-023 and supports advancing the program in patients,” said Dr. David Aviezer, Chief Executive Officer of Orvida Pharma, in a statement. “With no approved therapies available today, patients face a profound unmet medical need. We believe KM-023 has the potential to become the first targeted treatment for this condition.”

The Devastating Reality of Olmsted Syndrome

Olmsted syndrome is an ultra-rare and progressive genetic disorder, with fewer than 100 cases documented worldwide since it was first described in 1927. The disease is characterized by severe, painful thickening of the skin on the palms of the hands and soles of the feet, a condition known as palmoplantar keratoderma. This thickening often leads to deep, painful cracks and fissures that can make walking or using one's hands an agonizing ordeal, severely limiting mobility and daily function.

The syndrome's impact extends beyond the hands and feet. Patients often develop rough, scaly skin patches around the mouth, nose, eyes, and genital areas. In the most severe cases, the disease can cause constricting bands to form around fingers and toes, leading to deformities and even spontaneous amputation. The constant pain, intense itching, and recurrent infections from broken skin create a relentless burden, profoundly affecting quality of life and often leading to social isolation.

Currently, there is no cure. Treatment is a frustrating cycle of symptom management, offering only partial and temporary relief. Patients rely on a combination of topical creams to soften the skin, systemic retinoids that carry significant side effects, and, in some cases, surgical removal of the thickened skin, which often grows back. This lack of effective options highlights the critical importance of developing a targeted therapy that addresses the root cause of the disease.

A Targeted Attack on a Genetic Driver

Orvida Pharma’s KM-023 represents a paradigm shift from symptomatic relief to a targeted, molecular approach. Modern genetic research has identified that many cases of Olmsted syndrome are caused by gain-of-function mutations in the TRPV3 gene. This gene provides instructions for making a protein that forms a channel, or pore, on the surface of skin cells, regulating the flow of calcium ions.

In Olmsted syndrome, mutations cause the TRPV3 channel to be overactive, leading to the uncontrolled skin cell growth and thickening that defines the disease. KM-023 is a highly specific oral TRPV3 inhibitor, a molecule designed to block this overactive channel and normalize skin cell function from the inside out.

This scientific approach is what makes the initiation of the patient trial so compelling. “TRPV3 plays a key role in the underlying disease biology, and targeting this pathway with KM-023 represents a compelling therapeutic approach,” commented Prof. Edel O’Toole, MD, PhD, FRCP, of Queen Mary University of London, a leading dermatologist and an investigator in the clinical program. “These early safety data are encouraging and support the continued evaluation of KM-023 in patients with Olmsted syndrome.”

From Healthy Volunteers to Patient Dosing

The journey of KM-023 to patient trials began with a meticulously designed Phase 1a study conducted in France. The randomized, placebo-controlled trial involved 30 healthy volunteers. In cohorts receiving single ascending doses, no treatment-related adverse events were reported. In cohorts receiving multiple doses twice daily for up to five days, only two mild and transient adverse events were observed, neither of which required intervention.

These encouraging safety and tolerability results gave Orvida the green light to proceed to the Phase 1b portion of the trial. This global study, now underway at sites in the United Kingdom, the U.S., and Europe, will enroll patients diagnosed with Olmsted syndrome. Participants will receive KM-023 twice daily for 12 weeks.

The primary goal is to continue assessing the drug's safety in patients, but investigators will also be closely monitoring for exploratory signs of clinical activity—the first hints that the drug may be alleviating the disease's brutal symptoms. The trial, conducted under protocols approved by the FDA, MHRA, and ANSM, is a critical step in determining if the scientific promise of TRPV3 inhibition can translate into real-world clinical benefit. The company expects to release topline results from this study in the third quarter of 2026.