DUBLIN, Ireland, July 8, 2026
Keenova Therapeutics plc has announced positive Phase 3 clinical trial results for XIAFLEX® (collagenase clostridium histolyticum) in the treatment of plantar fibromatosis (Ledderhose disease), marking a significant milestone toward what could become the first approved pharmacological therapy for this chronic and progressive connective tissue disorder. The pivotal double-blind, placebo-controlled Phase 3 study successfully met its primary endpoint, demonstrating a statistically significant and clinically meaningful reduction in foot pain compared with placebo, while also achieving multiple key secondary endpoints evaluating physical function and activity limitations. The encouraging findings strengthen Keenova’s plans to submit a supplemental application to the U.S. Food and Drug Administration (FDA) during the fourth quarter of 2026, supporting expansion of the approved indications for XIAFLEX. Plantar fibromatosis currently has no approved drug treatments, leaving patients dependent on symptom management or surgery, making these positive clinical results particularly important for individuals affected by this debilitating disease.
Phase 3 Trial Demonstrates Significant Pain Relief and Functional Improvement
The EN3835-309 Phase 3 clinical trial enrolled 436 patients diagnosed with plantar fibromatosis who presented with measurable fibrous nodules affecting the plantar fascia. Participants were randomly assigned to receive either XIAFLEX® or placebo and underwent up to two treatment sessions administered at least 28 days apart. The study met its primary endpoint by demonstrating statistically significant improvement in Average Daily Pain Intensity using the Numeric Rating Scale (NRS) compared with placebo. In addition, the trial achieved important ranked secondary endpoints measuring difficulty and activity limitation using the Foot Function Index (FFI), further confirming meaningful improvements in patient mobility and daily function.
Additional secondary analyses also showed statistically significant improvements across pain severity, disease burden, treatment satisfaction, global assessments of clinical improvement, and reduction in nodule characteristics, providing comprehensive evidence supporting the therapeutic potential of XIAFLEX. Importantly, the safety profile remained consistent with previously approved indications, with most adverse events classified as mild to moderate, and investigators reported no treatment-related serious adverse events, reinforcing the product’s established safety profile.
Potential First Approved Therapy for Plantar Fibromatosis
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Plantar fibromatosis, also known as Ledderhose disease, is a chronic fibrotic disorder characterized by the formation of collagen-rich nodules within the plantar fascia that progressively impair walking, cause persistent pain, and reduce quality of life. Current treatment options remain limited to orthotics, pain medications, steroid injections, radiation therapy, or surgery, with no FDA-approved pharmacological therapies currently available. Keenova believes approximately 300,000 patients are expected to seek medical treatment for plantar fibromatosis in 2028, the year the company anticipates launching XIAFLEX for this new indication, pending regulatory approval. XIAFLEX is already approved by the FDA for selected urological and orthopedic conditions, providing an established clinical foundation for expanding its therapeutic applications.
Company leadership stated that the positive Phase 3 findings represent a major step toward addressing a significant unmet medical need while broadening the company’s specialty therapeutics portfolio. If approved, XIAFLEX could become the first disease-targeted injectable therapy specifically indicated for plantar fibromatosis, offering physicians and patients a minimally invasive alternative to surgery while expanding treatment options for a condition that has historically lacked effective pharmacological intervention. The successful trial further strengthens Keenova Therapeutics’ position in specialty pharmaceutical innovation and highlights the company’s continued commitment to developing therapies that improve outcomes for patients living with rare and underserved diseases.
Source: Keenova Therapeutics press release
