Xiaflex Meets Phase III Primary Endpoint in Plantar Fibromatosis, Setting Stage for First-Ever FDA Approval
核心洞察
Keenova Therapeutics (搜索)' Xiaflex met its primary endpoint of reducing average daily pain intensity on the NRS in a pivotal Phase III trial for plantar fibromatosis (搜索), with results described as statistically significant and clinically meaningful.
The 436-participant EN3835-309 PFI trial also met key ranked secondary endpoints on the Foot Function Index, with no treatment-related serious adverse events reported.
Plantar fibromatosis (搜索) currently has no approved pharmacological treatment worldwide; Keenova plans to submit an FDA application in Q4 2026 with an anticipated launch in 2028.
Keenova Therapeutics (搜索) announced positive results from its pivotal Phase III EN3835-309 PFI trial of XIAFLEX (collagenase clostridium histolyticum) for the treatment of plantar fibromatosis (搜索), a chronic and progressive condition also known as Ledderhose disease (搜索). The trial met its primary endpoint, demonstrating a statistically significant and clinically meaningful improvement in pain versus placebo as measured by the Average Daily Pain Intensity on the Numeric Rating Scale (NRS). The result positions the Ireland-based branded therapeutics company to file for a new FDA indication in the fourth quarter of 2026 — a milestone that, if successful, would create the first regulated pharmacological treatment for a condition that currently has no approved drug therapy anywhere in the world.
"We are excited to share the positive outcome for our Phase 3 clinical trial of plantar fibromatosis (搜索), a disease for which limited treatment options exist beyond symptom relief measures or surgery," said Dr. Marek Honczarenko, Executive Vice President and Chief Scientific Officer at Keenova. "With these encouraging results, we intend to submit our application for this indication to the FDA in the fourth quarter of 2026 as part of an effort to expand our XIAFLEX portfolio and help address unmet patient needs."
Trial Design and Key Findings
The double-blind, placebo-controlled EN3835-309 PFI trial enrolled 436 participants with plantar fibromatosis (搜索) and at least one measurable, hard or firm, palpable fibrous nodule on clinical examination. Participants were randomly assigned to receive up to two injections of XIAFLEX or placebo, with each treatment separated by a minimum of 28 days.
Beyond the primary pain endpoint, the trial met key ranked secondary endpoints related to difficulty and activity limitation as measured by the Foot Function Index (FFI) scale. The treatment benefit was further supported by statistically significant improvements across additional secondary measures, including the FFI pain subscale, patient global assessments of improvement and disease severity, treatment satisfaction, and nodule characteristics.
The safety profile of XIAFLEX in this study was consistent with the known safety profile from its approved indications. Most adverse events were rated by investigators as mild to moderate, and no treatment-related serious adverse events occurred.
A Condition Without Pharmacological Options
Plantar fibromatosis (搜索) is a hyperproliferative fibrous tissue disorder resulting in the formation of collagen nodules along the plantar fascia, the thick connective tissue that supports the arch of the foot. The condition is chronic and progressive, leading to pain, walking impairment, and reductions in quality of life. Current management options consist entirely of off-label or procedural interventions — including custom orthotics, topical treatments, over-the-counter pain and anti-inflammatory medications, radiation therapy, steroid injections, and ultimately surgery to remove the nodules — none of which carry regulatory sanction for this indication.
XIAFLEX is already FDA-approved for Dupuytren's contracture (2010) and Peyronie's disease (2013), both conditions involving pathological collagen accumulation. The enzyme degrades type I and type III collagen fibrils directly, disrupting the fibrous nodules that cause pain and functional limitation. This established mechanism provides a plausible rationale for its application in plantar fibromatosis (搜索) and brings a well-characterized safety database to the regulatory path.
Commercial Outlook and Next Steps
Based on claims data and projections, Keenova believes approximately 300,000 people will see a healthcare provider for plantar fibromatosis (搜索) in 2028, the anticipated launch year for the indication. The planned Q4 2026 FDA submission represents the next material milestone; a standard 12-month review clock would align with the projected 2028 launch timeline.
The company has not disclosed specific effect sizes, p-values, or nodule reduction data, which limits independent assessment of the magnitude of benefit. Full data presentation will be necessary before the clinical community can evaluate how the observed pain reduction compares to what patients currently achieve with existing symptom management approaches. Nevertheless, the result strengthens Keenova's strategy of extending the XIAFLEX franchise into additional collagen-driven conditions, building on the asset's established regulatory and commercial infrastructure across rheumatology and urology.