Orvida Pharma wins FDA RDEP entry for ontivatrep in Olmsted

Orvida Pharma has announced that the FDA has accepted its lead candidate, ontivatrep (KM-023), into the Rare Disease Evidence Principles (RDEP) process for Olmsted syndrome. The Israel-based clinical-stage biotech said acceptance allows it to engage directly with the FDA on the evidence package required to support a potential approval for the ultra-rare genetic skin disease, which currently has no approved treatments.

Olmsted syndrome is characterised by severely thickened and painful skin on the palms and soles, a condition that can restrict mobility, impair quality of life and, in a subset of patients, prove life-threatening. The genetic basis of the disorder and the small patient population make conventional clinical development pathways challenging, which is precisely the context the RDEP process was designed to address.

What the RDEP process offers

The RDEP framework is intended to give sponsors of rare-disease therapies greater clarity on the evidence standards the FDA will apply, before significant development capital is committed. Under the process, accepted sponsors meet with the relevant FDA review team to map out the data needed to demonstrate substantial evidence of effectiveness. Depending on the disease and the candidate, this can mean a single adequate and well-controlled study supported by confirmatory evidence, which may include mechanistic data, biomarker findings, natural history studies or expanded access outcomes.

For Orvida, RDEP entry is a meaningful de-risking step. The company is developing ontivatrep as a highly specific oral inhibitor of TRPV3, a transient receptor potential channel implicated in the aberrant keratinocyte signalling that drives Olmsted syndrome pathology. In April 2026, the company reported favourable Phase 1a safety data from a randomised, placebo-controlled study in 30 healthy volunteers. A Phase 1b trial in patients with Olmsted syndrome is now under way across sites in Europe and the United States, with topline results anticipated around the end of 2026.

"The process provides an opportunity to engage with the FDA on the evidence needed to support potential approval, an important consideration in developing treatments for ultra-rare diseases with significant unmet medical need," said David Aviezer, chief executive of Orvida Pharma.

Competitive and regulatory landscape

The rare and severe genodermatosis space has attracted increasing attention from small-cap biotechs and academic spinouts over the past several years, driven in part by the incentives available under the FDA's orphan drug and rare paediatric disease frameworks. Olmsted syndrome is among the most severe of the keratodermas, and the absence of any approved systemic or topical therapy represents a clear commercial opportunity for the first entrant to demonstrate clinical benefit. Ontivatrep's oral formulation and TRPV3 selectivity profile differentiate it from broader anti-inflammatory approaches, though the clinical effect size in patients remains to be established when Phase 1b data read out.

Orvida will present at BIO-Europe 2026 in Cologne in November and at the Jefferies Global Healthcare Conference in London later the same month, making the year-end Phase 1b readout the next significant catalyst for investors monitoring the programme.