Incyte and Syndax Announce FDA Approval of Niktimvo (axatilimab-csfr) for the Treatment of Chronic Graft-Versus-Host Disease (GVHD)

Incyte and Syndax Pharmaceuticals announced that the U.S. Food and Drug Administration (FDA) has approved Niktimvo (axatilimab-csfr), an anti-CSF-1R antibody, for the treatment of chronic graft-versus-host disease (GVHD) after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg (88.2 lbs.).

“With the approval of Niktimvo, patients with chronic GVHD whose disease has progressed after prior therapies, now have a new treatment option with a novel mechanism of action to help address the serious and devastating complications associated with this disease,” said Hervé Hoppenot, Chief Executive Officer, Incyte. “Niktimvo is Incyte’s second approved treatment for chronic GVHD, underscoring our continued commitment to advancing the development of new medicines on behalf of patients with this disease and the medical community.”

Chronic GVHD is a serious condition that can occur after an allogeneic stem cell transplant (the transfer of stem cells from a donor) in which the donated cells initiate an immune response and attack the transplant recipient’s organs. Chronic GVHD is a leading cause of significant morbidity and mortality after an allogeneic stem cell transplant and is estimated to develop in approximately 42% of transplant recipients, affecting approximately 17,000 patients in the U.S. Of those patients who develop chronic GVHD, nearly 50% require at least three lines of treatment, emphasizing the need for additional effective treatment options.

“The approval of Niktimvo represents a significant treatment advancement for patients with chronic GVHD who have failed at least two lines of previous therapy,” said Michael A. Metzger, Chief Executive Officer, Syndax. “We look forward to bringing this first-in-class anti-CSF-1R antibody to patients in need of new treatment options, while also continuing to explore axatilimab’s potential in combination with other standard of care therapies for chronic GVHD and in other indications.”

The FDA approval was based on data from the global AGAVE-201 study evaluating the safety and efficacy of Niktimvo in 241 adult and pediatric patients with refractory chronic GVHD who received at least two prior lines of systemic therapy. The trial met the primary endpoint across all cohorts receiving Niktimvo. Results from the study showed durable responses across all organs studied and patient subgroups. Among patients who received Niktimvo at the approved dose of 0.3 mg/kg every two weeks (N=79), 75% achieved an overall response rate (ORR) within the first six months of treatment, with a median time to response of 1.5 months. Additionally, 60% maintained a response at 12 months (measured from first response to new systemic therapy or death, based on the Kaplan Meier estimate). The trial also met a key exploratory endpoint, with a majority (56%) of patients achieving a ≥7-point improvement in the modified Lee Symptom Scale (mLSS) score. Organ-specific complete and partial responses were demonstrated across all organs studied that are affected by chronic GVHD, including lower gastrointestinal (GI), upper GI, esophagus, joints/fascia, mouth, lungs, liver, eyes and skin.

Serious adverse reactions occurred in 44% of patients who received Niktimvo (N=79). Serious adverse reactions observed in >2 patients included infection (pathogen unspecified), viral infection and respiratory failure. Permanent discontinuation of Niktimvo due to an adverse reaction occurred in 10% of patients and dose reduction due to adverse reaction occurred in 8% of patients. Dose interruptions due to an adverse reaction occurred in 44% of patients. The adverse reactions leading to dose interruption in >2 patients were viral infection, infection (pathogen unspecified), bacterial infection, musculoskeletal pain and pyrexia.

The most common (≥15%) adverse reactions, including laboratory abnormalities, were increased aspartate aminotransferase (AST), infection (pathogen unspecified), increased alanine aminotransferase (ALT), decreased phosphate, decreased hemoglobin, viral infection, increased gamma glutamyl transferase (GGT), musculoskeletal pain, increased lipase, fatigue, increased amylase, increased calcium, increased creatine phosphokinase (CPK), increased alkaline phosphatase (ALP), nausea, headache, diarrhea, cough, bacterial infection, pyrexia and dyspnea.

“Advanced chronic GVHD is characterized by the development of fibrotic tissue across multiple organ systems, including most commonly the skin and mucosa, and can be extremely difficult to treat, leading to high rates of morbidity and mortality,” said Daniel Wolff, M.D., Ph.D., Head of the GVHD Center at the University Hospital Regensburg. “I am excited that Niktimvo is designed to specifically target key drivers of inflammation and fibrosis in chronic GVHD, and I am highly encouraged by the robust responses observed across all organs and patient subgroups within the heavily pre-treated population enrolled in the AGAVE-201 trial. I look forward to having a new and differentiated treatment option for my patients who need additional therapies to address this very difficult to manage, debilitating, disease.”

The Biologics License Application (BLA) for Niktimvo for the treatment of chronic GVHD after failure of at least two prior lines of systemic therapy in adult and pediatric patients weighing at least 40 kg (88.2 lbs) was reviewed by the FDA under Priority Review. The FDA grants Priority Review designation to applications for medicines that, if approved, would treat a serious condition and provide significant improvements in the safety or effectiveness of the treatment.

In the United States, Niktimvo will be co-commercialized by Incyte and Syndax Pharmaceuticals. Incyte has exclusive commercialization rights for Niktimvo outside of the U.S.

To facilitate patient dosing and limit product waste, following the FDA’s approval of Niktimvo (as a 50mg vial), Incyte and Syndax will seek approval to launch two smaller vial sizes. Following FDA approval of the new vial sizes, the Companies anticipate launching Niktimvo in the U.S., no later than early first quarter 2025.