Keenova’s pivotal Phase 3 trial, EN3835-309 (NCT06151197), met its primary and key secondary endpoints, showing that XIAFLEX provided meaningful reductions in foot pain and improvements in function in patients with plantar fibromatosis, with an overall safety profile consistent with the drug’s approved indication.
Written By: Anamika Koshti, Pharm D
Reviewed By: Pharmacally Editorial Team
Keenova Therapeutics plc announced on July 8, 2026, positive topline results from its pivotal Phase 3 EN3835-309 (NCT06151197) trial evaluating XIAFLEX (collagenase clostridium histolyticum) for plantar fibromatosis, a chronic condition in which excess collagen forms painful nodules in the connective tissue supporting the arch of the foot. The study met its primary and key ranked secondary endpoints, with additional secondary measures also showing statistically significant improvements, supporting the company’s planned FDA submission in the fourth quarter of 2026. If approved, XIAFLEX could become the first pharmacological treatment for plantar fibromatosis. The therapy contains collagenase clostridium histolyticum, an enzyme that breaks down excess collagen within the fibrous nodule following local injection.
Trial Details
EN3835-309 was a randomized, double-blind, placebo-controlled Phase 3 trial evaluating the efficacy, safety, and tolerability of XIAFLEX in adults with plantar fibromatosis. The study enrolled 436 participants with at least one measurable, hard or firm palpable fibrous nodule confirmed by clinical examination. Participants were randomized to receive XIAFLEX or placebo, with up to two treatments administered at least 28 days apart. Throughout the study, participants recorded daily pain scores using the Numeric Rating Scale (NRS) and completed the Foot Function Index (FFI), Patient Global Impression of Severity (PGIS), Patient Global Impression of Change (PGIC), and treatment satisfaction questionnaires.
Efficacy Results
The trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in Average Daily Pain Intensity compared with placebo as measured by the Numeric Rating Scale. It also achieved key ranked secondary endpoints related to difficulty and activity limitation on the Foot Function Index. Additional statistically significant improvements were observed in the FFI pain subscale, global assessments of disease severity and improvement, treatment satisfaction, and nodule characteristics.
Safety Profile
The safety findings were consistent with the known safety profile of XIAFLEX. Most adverse events were mild to moderate, and there were no treatment-related serious adverse events. XIAFLEX is currently approved by the U.S. Food and Drug Administration for selected urological and orthopedic indications, and Keenova plans to expand its label to include plantar fibromatosis.
Clinical Implications
“We are very pleased with the positive results of our Phase 3 clinical trial of plantar fibromatosis, a condition for which there are few treatment options other than surgery or relief of symptoms,” said Dr. Marek Honczarenko, Executive Vice President and Chief Scientific Officer at Keenova. He said the company plans to submit an FDA application for the indication in the fourth quarter of 2026.
Keenova estimates that approximately 300,000 people will seek medical care for plantar fibromatosis in 2028, the year it expects to launch XIAFLEX if the therapy receives FDA approval.
About Plantar Fibromatosis
Plantar fibromatosis, also known as Ledderhose disease, is a chronic, progressive disorder characterized by collagen nodules that develop along the plantar fascia, causing pain, impaired walking, and reduced quality of life. No pharmacological treatment is currently approved. Current management includes orthotics, topical therapies, over-the-counter pain medications, radiation therapy, steroid injections, and surgery in severe cases.
Keenova is headquartered in Dublin, Ireland, with U.S. manufacturing facilities in Louisiana, New Jersey, New York, Pennsylvania, and Wisconsin.
What This Means for Patients?
People living with plantar fibromatosis currently have limited treatment options beyond symptom management and surgery. If approved, XIAFLEX could become the first drug specifically indicated for the condition, offering a non-surgical treatment shown in this Phase 3 study to reduce pain and improve foot function. Patients could gain access to the therapy as early as 2028, subject to FDA approval.
Reference
About the Writer
Anamika Koshti (LinkedIn) is a PharmD professional and healthcare writer with interests in clinical research, pharmacovigilance, and evidence-based medicine. She has authored peer-reviewed publications on Alzheimer’s disease and PCOS, presented research at national conferences, and gained hands-on experience in medical content development and clinical data interpretation. She is committed to translating complex medical research into accurate, accessible content for healthcare professionals and patients.