FDA Approves Incyte, Syndax's Niktimvo for Graft-Versus-Host Disease

Incyte has recently broadened its offerings for graft-versus-host disease (GVHD) with the introduction of a new treatment, Niktimvo, in collaboration with Syndax Pharmaceuticals. This new drug, a CSF-1R inhibitor known as axatilimab, received FDA approval to treat chronic GVHD (cGVHD) in patients who have not responded to at least two previous lines of systemic therapy.

Niktimvo's approval follows its successful performance in the phase 2 AGAVE-201 trial. In this study, patients who received the recommended dose of 0.3 mg/kg every two weeks experienced an overall response rate of 75%. The median time to observe a first response was 1.5 months, and the median duration of the response was 1.9 months before disease progression, mortality, or need for new systemic treatments. Impressively, 60% of patients who responded remained alive without requiring new systemic therapy for at least one year from their initial response.

Interestingly, the trial revealed that higher doses of Niktimvo resulted in lower overall response rates, a relatively uncommon occurrence in drug development. Despite advancements in treating chronic GVHD, a significant unmet need persists for patients unresponsive to earlier treatments. Hervé Hoppenot, CEO of Incyte, emphasized that axatilimab's unique mechanism presents a novel treatment approach that could benefit patients suffering from this severe condition.

Niktimvo functions by targeting the CSF-1 receptor, a cell surface protein implicated in the activities of monocytes and macrophages, believed to contribute to the fibrotic processes underlying cGVHD. Prior to Niktimvo, the FDA had approved Daiichi Sankyo's Turalio, another CSF-1R inhibitor, but for a rare cancer known as tenosynovial giant cell tumor.

Recognizing the potential of this mechanism in GVHD, Incyte partnered with Syndax Pharmaceuticals in 2021 through a co-development and co-commercialization agreement. While Niktimvo is currently approved as a third-line treatment, Incyte and Syndax have broader plans. This year, they aim to initiate a phase 3 trial for a combination therapy of Niktimvo and steroids, and a phase 2 trial combining Niktimvo with Jakafi for first-line patients.

Incyte's Jakafi received FDA approval in 2021 as a second- or third-line therapy for cGVHD. Recent final results from the three-year phase 3 REACH3 trial, which supported this approval, showed that Jakafi reduced the risk of treatment failure or death by 64% compared to the best available treatment in steroid-refractory cGVHD. However, the trial did not observe a significant difference in mortality risk between the two groups, likely due to approximately half of the control group patients switching to Jakafi.

With competitive pressures facing Jakafi's primary indication for myelofibrosis, GVHD and polycythemia vera have emerged as the main growth areas for this JAK inhibitor. The introduction of Niktimvo further strengthens Incyte's portfolio in addressing GVHD, providing new hope for patients who have exhausted other treatment options.