No Safety, Tolerability Problems Detected in Phase 1 Study of Niktimvo in Japanese Men

A single dose of Niktimvo (axatilimab) was well tolerated in a phase 1 study that enrolled 20 healthy patients in Japan, according to results reported in Clinical Drug Investigation last month.

The FDA approved Niktimvo in August 2024 as a treatment for chronic graft-versus-host disease (cGVHD) after two prior lines of treatment. Colony-stimulating factor 1 receptor (CSF1R)-dependent monocytes and macrophages are believed to play an important causative role in cGVHD, a complication of allogeneic (from another person) hematopoietic stem-cell transplantation. Niktimvo is a monoclonal antibody that blocks CSF1R.

Corresponding author Kazumi Suzukawa, M.D., Ph.D., a medical director at Incyte, the maker of Niktimvo, and colleagues noted that a detailed study of the safety, pharmacokinetics, and pharmacodynamics of Niktimvo was conducted in the Netherlands, with the results presented in 2017. But Suzukawa and colleagues said that whether those results apply to Japanese patients “remains unknown, necessitating further study to support a future clinical trial in Japanese patients with cGVHD.”

The researchers enrolled 20 participants into their phase 1 between March 15 and March 23, 2023. The participants were healthy Japanese men between the ages of 19 and 51. All of them were included in the safety and pharmacodynamics part of the study, and 15 were included in the pharmacokinetics and immunogenicity analysis. The researchers randomly assigned the participants so six received a single infusion of a low dose of Niktimvo (0.3 milligrams [mg] per kilogram [kg] of bodyweight); nine, a higher dose (1.0 mg/kg); and five, a placebo.

The results reported by Suzukawa and colleagues showed that three participants who received axatilimab experienced treatment-emergent adverse events (TEAEs) during the study. One participant receiving the low dose of Niktimvo experienced nasopharyngitis (grade 2), which was not related to the Niktimvo in the view of the researchers. Two participants who received the higher dose experienced TEAEs; one had an increase in amylase levels (grade 1), and another had a headache (grade 1). All TEAEs resolved by the end of the study, and none were deemed serious. Four days after the infusion, amylase levels increased by approximately 30% in the study participants who received the higher dose of Niktimvo, but levels returned to normal 22 days after the infusion.

These are safety results among healthy volunteers. The phase 2 trial, called AGAVE-201, that led to Niktimvo’s approval last year enrolled patients with recurrent or refractory cGVHD. The FDA-approved label for the drug says that infusion-related reactions, including hypersensitivity reactions, occurred in 18% of patients who received Niktimvo in the AGAVE-201 clinical trial, with Grade 3 or 4 reactions occurring in 1.3%. Results of AGAVE-201 that were reported in the New England Journal of Medicine in September 2024 showed adverse events led to discontinuation of the drug in 6% of those who received the 0.3 mg/kg dose and in 22% of those who received the 1 mg/kg dose.

Four days after the infusion, amylase levels increased by approximately 30% in the study participants who received the higher dose of Niktimvo, but levels returned to normal 22 days after the infusion.

Some of the pharmacokinetic measures suggested greater than dose-proportional effects from Niktimvo, while others suggested a dose-proportional pharmacokinetic response to the drug. One of the participants who received the low-dose version developed antibodies against Niktimvo, but the researchers said the antibodies didn’t affect the drug’s pharmacokinetics.

Colony-stimulating factor F-1 (CSF-1) and interleukin-34 levels increased in a dose-dependent manner following infusion of Niktimvo, according to the pharmacodynamic analysis conducted by Suzukawa and colleagues, while both remained below the limit of detection in participants who received placebo. The number of nonclassical monocytes increased temporarily, peaking at four hours after infusion, but then fell to below detection limits three days after the infusion.

Suzukawa and colleagues concluded that Niktimvo — they used the generic name — was “generally well tolerated” in healthy Japanese men with no TEAEs grade 3 or higher and “no notable trends or treatment-emergent safety concerns observed from clinical laboratory tests, vital signs, or 12-lead ECGs [electrocardiograms].”