Phase II AGAVE-201 Trial Shows Efficacy of Niktimvo for Refractory Chronic GVHD

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Results from the Phase II AGAVE-201 trial (NCT04710576) show that (Niktimvo) axatilimab monotherapy is effective and safe in the treatment of patients with recurrent or refractory chronic graft-versus-host-disease (GVHD) who previously failed multiple lines of therapy.^1,2 The data, published by The New England Journal of Medicine, showed significant responses across different dosing groups, particularly in patients with fibrotic manifestations.

“A high incidence of clinical response, including complete response, was seen in all involved organs,” the study authors wrote. “The response was durable and was not influenced by key baseline disease characteristics, including the severity of chronic GVHD, the number of organs involved, the duration of chronic GVHD, the number of previous treatments, or the failure of ibrutinib, ruxolitinib, or belumosudil therapy. Responses were seen in patients with inflammatory and fibrotic chronic GVHD manifestations, including prototypic fibrotic manifestations in the lung, esophagus, joints and fascia, and skin.”¹

Niktimvo was approved by the FDA in August 2024 to treat GVHD in patients who did not achieve a response to at least two prior lines of systemic therapy. Niktimvo was the first approved anti-CSF-1R antibody that targets the drivers of inflammation and fibrosis that are common in chronic GVHD.³

The multinational, pivotal, randomized AGAVE-201 trial analyzed Niktimvo in patients with recurrent or refractory chronic GVHD at doses of 0.3 mg per kilogram of body weight every two weeks (0.3-mg dose cohort), 1 mg per kilogram every two weeks (1-mg dose cohort), and 3 mg per kilogram every four weeks (3-mg dose cohort). A total of 241 patients were randomly assigned to the three dosing groups, with 80 patients assigned to the 0.3-mg dose cohort, 81 patients assigned to the 1-mg dose cohort, and 80 patients assigned to the 3-mg dose cohort.

The trial’s primary endpoint was overall response across the first six cycles, which would be achieved if the lower bound of the 95% confidence interval exceeded 30%, according to the investigators. The trial’s key secondary endpoint was patient-reported reduction in chronic GVHD symptom burden, as assessed by a decrease of more than 5 points on the modified Lee Symptom Scale.

Niktimvo achieved the trial’s primary endpoint across all dosing groups, with an overall response achieved by 74% (95% confidence interval [CI], 63 to 83) of patients in the 0.3-mg cohort, 67% (95% CI, 55 to 77) in the 1-mg dose cohort, and 50% (95% CI, 39 to 61) in the 3-mg dose cohort.

“Most patients with skin sclerosis, which affected more than 90% of the patients with chronic GVHD of the skin, had not just disease control but amelioration of skin sclerosis after treatment with [Niktimvo] as measured by the 2014 NIH Consensus secondary disease metrics, the patient-reported symptom scale, or both,” the study authors wrote. “About half the patients reported a rapid, clinically meaningful reduction in symptoms, which further supported the overall assessment of clinical efficacy and the potential for quality-of-life improvements in a patient population with severe complications related to both the disease and the treatment.”¹

A decrease of more than 5 points on the modified Lee Symptom Scale was observed across 60% of patients in the 0.3-mg cohort, 69% in the 1-mg dose cohort, and 41% of the patients in the 3-mg cohort. In terms of safety, the most common adverse events (AEs) were dose-dependent transient laboratory abnormalities associated with CSF1R blockade. AEs causing discontinuation of Niktimvo were reported by 6% of patients in the 0.3-mg dose cohort, 22% in the 1-mg dose cohort, and 18% in the 3-mg dose cohort.

“Refractory chronic GVHD with extensive fibrotic manifestations, a condition highly represented in the AGAVE-201 study, continues to present a major therapeutic challenge,” the study authors concluded. “The AGAVE-201 study showed that single-agent therapy with [Niktimvo] is effective for many patients with recurrent or refractory chronic GVHD, including those in whom standard-of-care therapies failed. Additional studies—such as the Study to Evaluate Axatilimab in Participants with Idiopathic Pulmonary Fibrosis (NCT06132256)—are warranted to evaluate [Niktimvo] in earlier treatment of chronic GVHD and autoimmune diseases in which CSF1R-driven macrophages contribute to inflammation and fibrosis.”¹

References

1. Wolff, D., et al. Axatilimab in Recurrent or Refractory Chronic Graft-versus-Host Disease. N Engl J Med 2024;391:1002-1014. Vol. 391 No. 11. Published September 18, 2024.

2. A Study of Axatilimab at 3 Different Doses in Participants With Chronic Graft Versus Host Disease (cGVHD) (AGAVE-201). ClinicalTrials.gov. June 14, 2024. https://clinicaltrials.gov/study/NCT04710576

3. Incyte And Syndax Announce U.S. FDA Approval Of Niktimvo™ (Axatilimab-Csfr) For The Treatment Of Chronic Graft-Versus-Host Disease (GVHD). Incyte. August 14, 2024. Accessed September 23, 2024. https://investor.incyte.com/news-releases/news-release-details/incyte-and-syndax-announce-us-fda-approval-niktimvotm-axatilimab