Axatilimab meets primary outcome in phase 2 chronic graft versus host disease trial

Article

Results from a pivotal phase 2 clinical trial revealed axatilimab met the primary outcome in all cohorts for graft versus host disease (GVHD) in pediatric and adult patients. Based on its safety and efficacy profile demonstrated in clinical trials, Syndax and Incyte intend to file a biologics license application (BLA) for axatilimab with the FDA by the end of 2023.

Axatilimab meets primary outcome in phase 2 chronic graft versus host disease trial | Image Credit: © teguhjatipras - © teguhjatipras - stock.adobe.com.

Axatilimab meets primary outcome in phase 2 chronic graft versus host disease trial | Image Credit: © teguhjatipras - © teguhjatipras - stock.adobe.com.

Axatilimab (Syndax Pharmaceuticals, Incyte) demonstrated positive topline results in pediatric and adult patients with chronic graft versus host disease (GVHD) following 2 or more prior lines of therapy, according to a recent press release from Syndax Pharmaceuticals.1

An immune response of donor-derived hematopoietic cells against recipient tissues, GVHD can be a potentially life-threatening complication of allogeneic hematopoietic stem cell transplantation that could “last for years,” according to Syndax. Axatilimab, an investigational monoclonal antibody, targets colony stimulating factor-1 receptor (CSF-1R). Inhibition of signaling through the CSF-1R receptor has reduced the number of disease-mediating macrophages and their respective monocyte precursors in pre-clinical models. The reduction of disease-mediating macrophages and monocyte precursors “has been shown to play a key role in the fibrotic disease process underlying diseases such as chronic GVHD and [idiopathic pulmonary fibrosis] IPF,” Syndax stated in the press release.1

The pivotal phase 2 AGAVE-201 trial (NCT 04710576), a global, dose-ranging trial that evaluated the safety, efficacy, and tolerability of axatilimab in 241 pediatric and adult patients (2 years and up), met the primary outcome in all cohorts.1,2 Trial participants with recurrent or refractory active GVHD that progressed after 2 prior treatments were included. The individuals were randomized to receive a distinct dose of axatilimab at either 0.3 mg/kg every 2 weeks, 1 mg/kg every 2 weeks, or 3mg/kg every 4 weeks. The participants, from 121 sites spanning across 16 countries had received a median of 4 prior systemic therapies. Seventy-four percent previously received ruxolitinib, 23% received belumosudil, and 31% received ibrutinib.1

For patients treated with axatilimab at the dose of 0.3 mg/kg every 2 weeks, the overall response rate (ORR) within the first 6 months of treatment was 74% (95% CI; 63,83). For a dosing of 1.0 mg/kg every 2 weeks, ORR in the first 6 months of treatment was 67% (95% CI; 55,77) while dosing at 3.0 mg/kg every 4 weeks demonstrated ORR of 50% (95% CI; 39,61). Across all cohorts, the trial achieved the primary outcome; patients of each dose group that achieved an objective response (defined by 2014 NIH Consensus Criteria for chronic GVHD by cycle 7 day 1).1

Syndax and Incyte plan to submit a biologics license application (BLA) to the FDA by year-end 2023 based on trial results and a pending agreement with the federal agency.1

"Chronic GVHD is a very common complication post allogeneic hematopoietic stem cell transplant that can have profound effects on patient medical burden and quality of life. More effective treatment options for this significant complication are desperately needed," said Carrie Kitko, MD, medical director, Pediatric Stem Cell Transplant Program, Vanderbilt-Ingram Cancer Center. “I am highly encouraged by these data which demonstrate robust responses in a heavily pre-treated patient population. These findings further support that axatilimab has the potential to provide a clinically meaningful response for patients suffering from this morbid condition.”1

Measure from first response to new systemic therapy or death, based on the Kaplan Meier estimate, Syndax also announced that of axatilimab-treated patients at a dose of 0.3 mg/kg, 60% maintained a response at 12 months. The median duration of response for this population “has not been reached,” according to the press release. Fifty-five percent of patients in the 0.3 mg/kg dose group experienced improvement in symptoms that was clinically meaningful (at least a 7-point decrease in the modified Lee chronic GVHD Symptom Scale score).1

An increase in aspartate aminotransferase, blood creatine phosphokinase, lipase, blood lactate dehydrogenase, alanine aminotransferase, and fatigue were adverse events in more than 20% of patients treated with axatilimab (n = 239). In the overall population, serious adverse events occurred in 101 patients (42.3%), while 37 patients (15.5%) that experienced adverse events discontinued study treatment. Fatigue was the only serious adverse event that occurred in more than 20% of patients in the 0.3 mg/kg dose group (n = 79). In this dose group, serious adverse events occurred in 30 patients (38%), while 5 patients (6.3%) that experienced adverse events discontinued study treatment.1

References:

  1. Syndax and Incyte announce positive topline results from the pivotal AGAVE-201 trial of axatilimab in chronic graft-versus-host disease. Syndax Pharmaceuticals. Press release. July 24, 2023. Accessed July 25, 2023. https://ir.syndax.com/news-releases/news-release-details/syndax-and-incyte-announce-positive-topline-results-pivotal
  2. A study of Axatilimab at 3 different doses in participants with chronic graft versus host disease (cGVHD) (AGAVE-201). ClinicalTrials.gov. Updated June 18, 2023. Accessed July 25, 2023. https://classic.clinicaltrials.gov/ct2/show/NCT04710576
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