FDA Approves Axatilimab for Patients With Chronic GVHD

• The FDA has approved axatilimab (Niktimvo) for patients with chronic graft-vs-host disease (cGVHD) after failure of at least 2 prior systemic therapies.
• The phase 2 AGAVE-201 trial (NCT04710576) serves as the basis of this approval as results demonstrated significant and durable responses with axatilimab.
• Particularly at a dose of 0.3 mg/kg every 2 weeks, axatilimab achieved the highest objective response rate (ORR; 74%), with rapid and sustained responses, meeting the primary end point across all dosage cohorts.

The FDA has approved axatilimab, an anti-CSF-1R antibody, for patients with cGVHD after failure of at least 2 prior lines of systemic therapy.¹

This regulatory decision is supported by findings from the phase 2 AGAVE-201 trial where axatilimab led to quick and durable responses in patients with recurrent or refractory cGVHD.² These findings were presented in a and showed that the ORR was 74% (95% CI, 63%-83%) when axatilimab was given at a dose of 0.3 mg/kg every 2 weeks (n = 80).

Axatilimab at a dose of 1.0 mg/kg every 2 weeks (n = 81) or 3.0 mg/kg every 4 weeks (n = 80) resulted in ORRs of 67% (95% CI, 55%-77%) and 50% (95% CI, 39%-61%), respectively. The primary end point of ORR in the first 6 cycles as defined by National Institutes of Health (NIH) 2014 Consensus criteria was met in all cohorts included in the study.

“Chronic graft-vs-host disease is a disease now known for almost 50 years, and we have not really had progress for the first 30 years,” explained Daniel Wolff, MD, senior physician, and professor at University Hospital Regensburg, Germany, in an interview with Targeted Oncology^TM. “[AGAVE-201] is 1 of the biggest phase 2 trials ever done in chronic graft-vs-host disease in terms of numbers. Looking at it in retrospect, we are kind of happy that the trial was designed in the way it [was]. It compared 3 different doses with 2 scheduled and explored axatilimab.”

Axatilimab showed a manageable toxicity profile at all doses analyzed with highest efficacy observed at the 0.3-mg/kg dose. Axatilimab was generally well tolerated, with a safety profile that was manageable and consistent with the mechanism of action of CSF-1R inhibition.

“The results [were] quite astonishing, in a way, [because] high responses were seen across all 3 cohorts. The surprise was that the lowest dose was accompanied with the highest response rates, between 60 to 70%.” added Wolff in the interview.

About the AGAVE-201 Trial

Patients with active cGVHD defined as 2014 NIH Consensus criteria who were at least 2 years of age who had received at least 2 prior lines of systemic treatment were enrolled in the phase 2 AGAVE-201 trial if they had a Karnofsky performance that was equal to or above 60% and adequate bone marrow and organ function. Patients were allowed concomitant use of corticosteroids, calcineurin inhibitors, and mTOR inhibitors, but it was not required.

A total of 241 patients were randomized to 1 of 3 doses/schedules at 121 clinical sites in 16 countries and 4 continents (North America, n = 51; Europe/Middle East, n = 58; Asia, n = 10; Australia, n = 2). These doses consisted of axatilimab 0.3 mg/kg every 2 weeks, 1.0 mg/kg every 2 weeks, and 3.0 mg/kg every 4 weeks.

Secondary end points evaluated in the study were duration of response, percent reduction in daily steroids dose, organ specific response rates, and validated quality-of-life assessments using the Modified Lee Symptom Scale.

Additional findings showed that the median time to response in the cohorts where axatilimab was given at doses of 0.3 mg/kg, 1.0 mg/kg, and 3.0 mg/kg was 1.7 months (range, 0.9-8.1), 1.9 months (range, 0.9-8.6), and 1.4 months (range, 0.9-5.6), respectively. In these cohorts, 60% (95% CI, 43%-74%), 60% (95% CI, 43%-74%), and 53% (95% CI, 30%-71%) of patients had responses that continued for at least 1 year, respectively. The median failure-free survival demonstrated with axatilimab was 17.3 months (95% CI, 14.2-not evaluable).

For safety, 6.3% of patients in the 0.3-mg/kg cohort had adverse effects (AEs) that led to dose decrease and 6.3% discontinued treatment due to their AEs. The most common AEs of any grade seen in at least 20% of patients in this cohort consisted of fatigue (22.8%), headache (19.0%), periorbital edema (2.5%), and COVID-19 (16.5%).

Laboratory abnormalities observed in the study included increased aspartate aminotransferase (13.9%), increased creatinine phosphokinase (11.4%), increased lipase (11.4%), increased lactate dehydrogenase (13.9%), increased alanine aminotransferase (12.7%), and increased amylase (3.8%). Further, 17.7% of patients had at least 1 related grade 3 or higher AE. One patient had an AE that led to death.

REFERENCES:

1. FDA approves axatilimab-csfr for chronic graft-versus-host disease. News release. FDA. August 14, 2024. Accessed August 14, 2024. https://tinyurl.com/3sn66tn3

2. Wolff D, Cutler C, Lee SJ, et al. Safety and efficacy of axatilimab at 3 different doses in patients with chronic graft-versus-host disease (AGAVE-201). Blood. 2023;142(suppl 1):1. doi:10.1182/blood-2023-186963