Keenova Therapeutics has reported that collagenase clostridium histolyticum (Xiaflex) met its primary endpoint in a pivotal Phase III trial for plantar fibromatosis — a condition also known as Ledderhose disease — positioning the Ireland-based branded therapeutics company to file for a new FDA indication in Q4 2026. Plantar fibromatosis currently has no approved pharmacological treatment anywhere in the world, meaning a successful approval would create the first regulated drug option for a chronic, progressive condition that causes painful collagen nodules along the plantar fascia and can ultimately require surgery.
The EN3835-309 PFI trial enrolled 436 participants with at least one measurable fibrous nodule and randomized them to receive up to two injections of collagenase clostridium histolyticum or placebo, separated by a minimum of 28 days. The primary endpoint — reduction in average daily pain intensity on the Numeric Rating Scale — was met with statistical significance and described as clinically meaningful. Key ranked secondary endpoints assessing difficulty and activity limitation on the Foot Function Index scale were also met, with additional statistically significant improvements reported across patient global assessments, treatment satisfaction, and nodule characteristics. No treatment-related serious adverse events occurred, and the safety profile was consistent with what has been established in Xiaflex's approved indications.
Competitive context
The current standard of care consists entirely of off-label or procedural interventions — orthotics, steroid injections, radiation therapy, and fasciectomy — none of which carry regulatory sanction for this indication. Collagenase clostridium histolyticum is already FDA-approved for Dupuytren's contracture (2010) and Peyronie's disease (2013), both conditions involving pathological collagen accumulation, which provides a plausible mechanistic rationale and a well-characterized safety database. The enzyme degrades type I and type III collagen fibrils directly, disrupting the fibrous nodules that cause pain and functional limitation. Cross-trial comparisons with prior collagenase programs are limited by differences in anatomy, patient population, and endpoint selection, but the existing approval history meaningfully de-risks the regulatory path.