Keenova Therapeutics has reported positive Phase 3 results for XIAFLEX in plantar fibromatosis, giving the company a late-stage regulatory path toward what could become the first approved pharmacological treatment for the chronic foot disorder also known as Ledderhose disease. The pivotal trial met its primary endpoint by showing a statistically significant and clinically meaningful reduction in pain compared with placebo.
The study also met key ranked secondary endpoints measuring difficulty and activity limitation through the Foot Function Index, while additional secondary measures supported improvements in pain, patient global assessments, treatment satisfaction and nodule characteristics. Keenova said the safety profile was consistent with the known safety profile of XIAFLEX in approved indications, with most adverse events rated as mild to moderate and no treatment-related serious adverse events reported.
The result is important because plantar fibromatosis has no approved drug therapy and is often managed through symptom-relief measures, orthotics, injections, radiation therapy or surgery. Keenova said it intends to submit an application to the United States Food and Drug Administration in the fourth quarter of 2026, positioning the programme as a potential portfolio-expansion opportunity for an already marketed collagenase therapy.
What did Keenova’s Phase 3 XIAFLEX trial show in plantar fibromatosis?
The Phase 3 trial, known as EN3835-309 PFI, was a double-blind, placebo-controlled study designed to assess whether XIAFLEX could reduce the intensity of foot pain in patients with plantar fibromatosis. The trial enrolled 436 participants who had at least one measurable, hard or firm, palpable fibrous nodule confirmed during clinical examination.
Participants were randomly assigned to receive either XIAFLEX or placebo. Each group received up to two treatments, with each treatment separated by at least 28 days. Patients recorded daily pain intensity using the Numeric Rating Scale, while several pre-specified follow-up visits collected functional and patient-reported outcomes through tools such as the Foot Function Index, Patient Global Impression of Severity, Patient Global Impression of Change and treatment satisfaction measures.
The primary endpoint focused on average daily pain intensity. Keenova said the trial demonstrated a statistically significant and clinically meaningful improvement in pain versus placebo, suggesting that the treatment effect was not merely numerical but relevant to patients’ day-to-day experience.
The trial also met key ranked secondary endpoints linked to difficulty and activity limitation. That matters because plantar fibromatosis is not only a pain condition. The nodules can interfere with walking, standing, footwear choice and mobility, so functional improvement is central to whether a treatment has real-world value.
Why does plantar fibromatosis create such a difficult treatment gap for patients?
Plantar fibromatosis is a chronic fibrous tissue disorder that causes collagen-rich nodules to form along the plantar fascia, the thick connective tissue that supports the arch of the foot. These nodules are benign, but they can become painful, progressive and functionally limiting.
The condition can be frustrating because even small nodules may cause discomfort when they press against footwear or bear weight during walking. Larger or more painful nodules can affect gait, daily mobility, exercise and quality of life. For patients who spend long hours standing, the impact can be much bigger than the size of the nodule suggests.
Current management is often conservative at first. Patients may use custom insoles, shoe modifications, topical treatments, anti-inflammatory medicines, steroid injections or physical measures intended to reduce pressure and discomfort. Radiation therapy and surgery may be considered in selected cases, but each has limitations.
Surgery can remove nodules, but recurrence, scarring, wound issues and prolonged recovery remain concerns. Because the plantar fascia is central to foot mechanics, aggressive intervention can create new problems even when the original nodule is treated. That is why a non-surgical pharmacological option could be meaningful if it offers durable pain and function improvement with acceptable safety.
How could XIAFLEX work differently from symptom-relief measures or surgery?
XIAFLEX is collagenase clostridium histolyticum, an injectable enzymatic therapy designed to break down collagen. In plantar fibromatosis, the underlying nodules are composed largely of excess collagen within the plantar fascia. The treatment rationale is therefore straightforward: target the collagen-rich nodule rather than only managing the symptoms caused by it.
This is different from orthotics or footwear modification, which reduce pressure but do not directly alter the nodule. It is also different from surgery, which physically removes tissue but introduces procedural risks and recovery burden. A collagenase-based approach sits between conservative management and invasive intervention.
XIAFLEX already has a regulatory and clinical history in collagen-driven disorders. It is approved in the United States for Dupuytren’s contracture and Peyronie’s disease, both conditions involving abnormal collagen structures. That history gives clinicians familiarity with the drug’s mechanism, administration concept and safety considerations.
However, plantar fibromatosis is anatomically and functionally different. The foot bears weight continuously, the plantar fascia is exposed to repetitive mechanical stress, and pain outcomes may depend on pressure distribution, nodule location and activity level. The Phase 3 data therefore matter because the company must prove the approach works specifically in this foot disorder rather than relying only on experience from other indications.
Why are pain and Foot Function Index improvements commercially important?
Pain reduction is the obvious endpoint because pain is one of the main reasons patients seek care. However, plantar fibromatosis becomes commercially and clinically more compelling when a therapy also improves function. A patient who has less pain but still cannot walk comfortably may not view the treatment as a major success.
The Foot Function Index adds that functional lens. It measures dimensions such as pain, disability and activity limitation, making it useful for conditions that affect mobility. By meeting key secondary endpoints on difficulty and activity limitation, the trial suggests that XIAFLEX may have produced benefits beyond a narrow pain score.
This is important for physicians because treatment decisions often depend on whether symptoms are severe enough to justify intervention. If XIAFLEX can show that it reduces both pain and functional burden, it could become relevant for patients who are not adequately helped by orthotics or pain medication but want to avoid surgery.
For payers, functional benefit also matters. A medicine for plantar fibromatosis may face reimbursement scrutiny if it is seen only as a comfort therapy. Evidence that it can improve mobility, reduce disability and delay or avoid more invasive procedures would strengthen the health-economic argument.
What does the safety profile suggest about XIAFLEX in this new indication?
Keenova said the safety profile in the Phase 3 plantar fibromatosis study was consistent with the known safety profile of XIAFLEX from approved indications. Most adverse events were described as mild to moderate, and no treatment-related serious adverse events were reported.
That is a useful signal because plantar fibromatosis treatment would likely occur in an outpatient setting and would need to be acceptable for patients with a chronic, non-life-threatening condition. The tolerance for serious risk is usually lower when the disease is painful and disabling but not malignant or immediately life-threatening.
Even so, collagenase therapy requires careful administration. Injecting an enzymatic treatment into fibrous tissue near important foot structures demands anatomical precision, clinician training and appropriate patient selection. Local reactions such as swelling, bruising, pain or tissue effects may still influence patient experience, even when serious complications are absent.
The long-term safety and durability of response will also matter. Patients and clinicians will want to know whether symptoms recur, whether nodules re-form, whether repeat treatment is needed and whether multiple injections change the risk profile. Those details will become more important if the product reaches regulatory review and eventual clinical use.
How could FDA submission in late 2026 shape the path toward launch?
Keenova plans to submit an application to the United States Food and Drug Administration in the fourth quarter of 2026. If the filing is accepted for review, the programme would move from clinical data announcement to formal regulatory assessment.
The agency will examine the full data package, including efficacy, safety, trial conduct, statistical analysis, manufacturing controls, dosing, administration procedure and proposed labelling. Because XIAFLEX is already an approved therapy in other indications, the review may benefit from existing knowledge of the product, but the plantar fibromatosis indication must still stand on its own evidence.
Potential label details will be especially important. The FDA could define eligible patients based on nodule characteristics, pain severity, functional limitation, dosing schedule or clinician training requirements. The exact label would influence how broadly physicians can use the treatment and how payers evaluate coverage.
Keenova has suggested that about 300,000 people may seek healthcare provider care for plantar fibromatosis in 2028, when the company expects to launch the product for the indication if approved. That figure indicates a meaningful specialty-market opportunity, but real adoption will depend on diagnosis rates, patient willingness, payer coverage and physician comfort with injection-based treatment in the foot.
How does this data expand the strategic value of the existing XIAFLEX franchise?
The positive Phase 3 result gives Keenova a potential way to extend the XIAFLEX franchise into another collagen-driven disorder. That is strategically attractive because developing a new indication for an established drug can be less risky than creating an entirely new molecule from scratch.
The existing product history may support manufacturing familiarity, clinician awareness and safety understanding. However, commercial execution in plantar fibromatosis will require a different care pathway from urology or hand surgery indications. The treating physician base could include podiatrists, foot and ankle orthopaedic surgeons, sports medicine physicians and other specialists involved in foot pain and soft-tissue disorders.
Keenova will also need to educate clinicians on identifying the right patients. Not every plantar nodule will need intervention, and not every patient with foot pain has plantar fibromatosis. Clear diagnostic criteria and training will be important to avoid inappropriate use.
The company’s broader rare and unaddressed disease strategy fits the indication. Plantar fibromatosis is not a mass-market primary care disease in the usual sense, but it is common enough to support a focused commercial opportunity if the treatment can become a recognised option before surgery.
What are the remaining uncertainties before XIAFLEX can become a plantar fibromatosis treatment?
The biggest uncertainty is regulatory outcome. Positive Phase 3 results improve the probability of approval, but they do not guarantee it. The FDA may ask detailed questions about effect size, durability, adverse events, injection technique, statistical robustness or the clinical meaning of patient-reported outcomes.
Durability will be another major question. Plantar fibromatosis can be chronic and progressive, and patients may want to know whether treatment benefit lasts months, years or only through the study follow-up period. If repeat treatment is needed, clinicians will need evidence on repeat-use safety and efficacy.
Comparative positioning is also uncertain. Since there is no approved pharmacological treatment, XIAFLEX may not need to beat an existing drug. However, it must still compete with conservative care, steroid injections, radiation therapy and surgery in real-world practice. Physicians will ask which patients should move from observation or orthotics to collagenase injection.
Reimbursement could also shape adoption. Payers may require documentation of pain severity, functional limitation, failed conservative treatment or confirmed diagnosis before covering therapy. If access is difficult, even strong clinical data could translate into slow uptake.
What is the expert assessment of Keenova’s XIAFLEX Phase 3 result?
Keenova’s positive Phase 3 result is a meaningful development because plantar fibromatosis has long lacked an approved drug treatment despite causing persistent pain and mobility problems for many patients. The combination of pain improvement, functional benefit and a safety profile consistent with existing XIAFLEX use gives the company a credible regulatory package to take forward.
The story is also commercially interesting because it uses a known collagenase therapy in a related collagen-driven condition. That reduces some scientific uncertainty, although it does not eliminate the need for careful regulatory review and indication-specific clinician training.
The most encouraging part of the data is that the trial met both the primary pain endpoint and key functional endpoints. In a foot disorder, function is not optional. Any treatment that reduces pain but fails to improve walking, activity and patient satisfaction would have limited appeal.
The caution is that important details remain undisclosed, including the exact magnitude of benefit, durability of response, subgroup performance, nodule-size changes and longer-term recurrence patterns. Those data will be important for physicians, payers and patients evaluating whether the treatment is worth adopting.
For now, Keenova has delivered a strong late-stage signal in an under-addressed condition. If the FDA accepts and approves the planned application, XIAFLEX could become the first pharmacological option for plantar fibromatosis and may shift treatment discussions away from a narrow choice between symptom management and surgery.
