FDA Approves Niktimvo™ for Chronic GVHD Treatment

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

Hervé Hoppenot, CEO of Incyte, highlighted that the approval marks a significant advancement for patients with chronic GVHD, offering a new treatment option with a novel mechanism of action. He emphasized that Niktimvo is Incyte's second approved treatment for the condition, demonstrating the company's commitment to developing new medicines for patients and the medical community.

Chronic GVHD is a serious condition that arises after an allogeneic stem cell transplant, where donated cells trigger an immune response that attacks the recipient's organs. It's a leading cause of morbidity and mortality post-transplant, affecting approximately 17,000 patients in the U.S. Nearly 50% of these patients require at least three lines of treatment, underscoring the need for additional effective therapies.

Michael A. Metzger, CEO of Syndax, expressed that the approval represents a significant advancement for patients who have not responded to previous therapies. He looks forward to providing this first-in-class anti-CSF-1R antibody to those in need and exploring its potential in combination with other treatments for chronic GVHD and other indications.

The FDA's approval was based on data from the global AGAVE-201 study, which evaluated the safety and efficacy of Niktimvo in 241 patients with refractory chronic GVHD who had undergone at least two prior lines of systemic therapy. The trial met its primary endpoint across all cohorts receiving the drug. Results indicated durable responses across all studied organs and subgroups. In particular, among those treated with the approved dose of 0.3 mg/kg every two weeks, 75% achieved an overall response rate (ORR) within six months, with a median time to response of 1.5 months. Additionally, 60% maintained their response at 12 months. A key exploratory endpoint showed that 56% of patients achieved a ≥7-point improvement in the modified Lee Symptom Scale (mLSS) score. Responses were observed across various organs affected by chronic GVHD, including the lower gastrointestinal (GI) tract, upper GI tract, esophagus, joints/fascia, mouth, lungs, liver, eyes, and skin.

Serious adverse reactions occurred in 44% of patients who received Niktimvo. The most common adverse reactions included increased aspartate aminotransferase (AST), unspecified infections, increased alanine aminotransferase (ALT), decreased phosphate, decreased hemoglobin, viral infections, increased gamma-glutamyl transferase (GGT), musculoskeletal pain, and increased lipase, among others. Permanent discontinuation due to adverse reactions occurred in 10% of patients, while dose reductions and interruptions due to adverse reactions were noted in 8% and 44% of patients, respectively.

Dr. Daniel Wolff, Head of the GVHD Center at the University Hospital Regensburg, commented on the difficulty of treating advanced chronic GVHD, which often involves fibrotic tissue development across multiple organ systems. He expressed optimism about Niktimvo's design to target key inflammation and fibrosis drivers in chronic GVHD and was encouraged by the robust responses observed in the AGAVE-201 trial.

Niktimvo's Biologics License Application (BLA) was reviewed by the FDA under Priority Review, which is granted to applications for medicines that would treat serious conditions and significantly improve treatment safety or effectiveness. In the U.S., Niktimvo will be co-commercialized by Incyte and Syndax Pharmaceuticals, with Incyte holding exclusive commercialization rights outside the U.S. To optimize patient dosing and minimize product waste, the companies plan to seek approval for two smaller vial sizes following the FDA’s approval of the 50 mg vial. The launch of Niktimvo in the U.S. is anticipated by early 2025.