For some transplant survivors, the hard part begins after the transplant. On 14 August 2024 the U.S. Food and Drug Administration approved axatilimab-csfr, sold as Niktimvo, for chronic graft-versus-host disease, or cGVHD, for patients, adult or pediatric, weighing at least 88.2 lbs. It is meant for people whose disease has progressed after at least 2 earlier systemic therapies.
The condition is a serious complication of allogeneic stem cell transplantation. Donor immune cells turn on the recipient’s tissues and damage organs. AJMC reported that GVHD affects approximately 42% of transplant recipients, and half of those patients need more than one treatment regimen. The need for new options is plain.
What the trial showed
The approval rests on AGAVE-201, a Phase 2 study, randomized, open-label and run at several centers, that tested 3 doses in people whose cGVHD kept returning or would not respond after at least 2 prior lines of therapy. The main measure was overall response rate, counting complete and partial responses.
Among the 79 patients who received the recommended dose, 75% responded (95% CI, 64-84). The median time to a first response was 1.5 months. Responses did not always last long: median duration was 1.9 months. Still, about 60% of those who responded went at least 12 months without dying or starting another systemic therapy.
Daniel Wolff, who leads the GVHD Center at University Hospital Regensburg, said he was encouraged by “robust responses observed across all organs and patient subgroups” in a heavily pre-treated group. He called it a “new and differentiated treatment option” for patients with a debilitating disease that is hard to manage.
Side effects and dosing
Safety needs a careful read. Among patients on axatilimab, 44% had serious adverse reactions. In 10% the drug was stopped permanently, and 8% needed a lower dose. Infection was the most common problem, along with raised liver enzymes, low phosphate and low haemoglobin, musculoskeletal pain and fatigue. AJMC also listed nausea, headache, diarrhea, cough, fever and shortness of breath.
The dose is 0.3 mg/kg with a ceiling of 35 mg, delivered through a 30-minute intravenous infusion every 2 weeks. Treatment continues until the disease progresses or toxicity becomes unacceptable.
Incyte filed the application, and the FDA gave it Priority Review. The drug also carries Orphan Drug and Fast Track designations. Incyte and Syndax Pharmaceuticals will sell it together in the US, initially in a 50 mg vial, and plan to seek approval for two smaller vial sizes to cut waste. Subject to that clearance, they expect the launch to arrive in the first quarter of 2025 at the latest. Hervé Hoppenot, Incyte’s chief executive, said patients whose disease has progressed now have a treatment that works through a new mechanism.
Axatilimab is not a cure, and the trial responses were short. The encouraging part is that people who had run out of choices now have another one. Patients should talk to their transplant team and consult their doctor about whether it suits them.
Sources
- FDA Approves Axatilimab for Chronic Graft-Versus-Host Disease (HCPLive)
- FDA Approves Axatilimab-csfr for Chronic Graft-vs-Host Disease (AJMC)
