The U.S. Food and Drug Administration (FDA) has granted approval to Niktimvo (axatilimab-csfr), an anti-CSF-1R antibody, for the treatment of chronic graft-versus-host disease (GVHD) in adult and pediatric patients weighing at least 40 kg (88.2 lbs.) after failure of at least two prior lines of systemic therapy. This approval marks a significant advancement in the treatment landscape for chronic GVHD, offering a novel mechanism of action to address the serious complications associated with the disease. The co-commercialization will be between Incyte and Syndax Pharmaceuticals.
Clinical Efficacy and Safety
The FDA's decision was primarily based on data from the global AGAVE-201 study, which evaluated the safety and efficacy of Niktimvo in 241 adult and pediatric patients with refractory chronic GVHD. These patients had previously undergone at least two lines of systemic therapy. The trial met its primary endpoint, demonstrating durable responses across all organs studied and patient subgroups.
In the cohort receiving the approved dose of 0.3 mg/kg every two weeks (N=79), 75% of patients achieved an overall response rate (ORR) within the first six months of treatment, with a median time to response of 1.5 months. Furthermore, 60% of patients maintained a response at 12 months, measured from the first response to new systemic therapy or death, based on the Kaplan Meier estimate. A key exploratory endpoint was also met, with 56% of patients achieving a ≥7-point improvement in the modified Lee Symptom Scale (mLSS) score. Organ-specific complete and partial responses were observed across various organs affected by chronic GVHD, including the lower and upper gastrointestinal tract, esophagus, joints/fascia, mouth, lungs, liver, eyes, and skin.
Serious adverse reactions occurred in 44% of patients who received Niktimvo (N=79). The most common adverse reactions (≥15%), 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.
Understanding Chronic GVHD
Chronic GVHD is a condition that can arise after an allogeneic stem cell transplant, where donor cells initiate an immune response, attacking the recipient's organs. It is a leading cause of morbidity and mortality post-transplant, affecting approximately 42% of transplant recipients in the U.S., which equates to about 17,000 patients. Nearly 50% of these patients require at least three lines of treatment, highlighting the urgent need for more effective therapeutic options.
Mechanism of Action and Further Studies
Niktimvo (axatilimab-csfr) is a first-in-class anti-CSF-1R antibody. Axatilimab is also being studied in frontline combination trials in chronic GVHD, including a Phase 2 trial with ruxolitinib (NCT06388564) and a Phase 3 combination trial with steroids expected to begin by year-end. Additionally, axatilimab is under investigation in a Phase 2 trial for patients with idiopathic pulmonary fibrosis (NCT06132256).
Commercialization and Availability
Incyte and Syndax Pharmaceuticals will co-commercialize Niktimvo in the United States. Incyte holds exclusive commercialization rights outside the U.S. To facilitate patient dosing and reduce product waste, the companies will seek approval for smaller vial sizes following the initial FDA approval of the 50mg vial. The launch of Niktimvo in the U.S. is anticipated no later than early first quarter 2025.
