FDA Grants Priority Review to Abatacept to Prevent Moderate to Severe Acute GVHD

The application has been assigned a Prescription Drug User Fee Act action date of December 23, 2021.

“While stem cell transplants are an effective treatment for aggressive leukemias and other hematologic malignancies, patients receiving stem cell transplants may have unrelated and human leukocyte antigens.” [HLA]-mismatched donors are at high risk of developing aGVHD,” said lead researcher Leslie Kean, MD, PhD, director of the Pediatric Stem Cell Transplantation Program, Boston Children’s Hospital/Dana-Farber Cancer Institute, in a press release. “There is a tremendous need to expand the stem cell donor pool by lowering the risk of aGVHD in both adults and children receiving unrelated donor stem cell transplants.”

Abatacept was investigated in the phase 2 ABA2 study, which evaluated whether aGVHD can be significantly reduced after HSCT by adding T-cell costimulation blockade to abatacept. The study concluded that the combination was safe and effective in reducing aGVHD and significantly improving aGVHD-related transplant outcomes. Data from the ABA2 study supports the BLA

Approximately 186 adult and pediatric patients with hematologic malignancies under 2 strata were enrolled in the multicenter, randomized, double-blind, placebo-controlled study. Patients were randomized to receive either standard GVHD prophylaxis with placebo or standard GVHD prophylaxis with abatacept. The primary endpoint assessed in the study was the proportion of patients with a cumulative incidence of severe aGVHD at Day 100+ post-transplant.2

The study’s secondary endpoints included the cumulative incidence of major infection, implantation, relapse, and overall survival, as well as the proportion of patients with Grade 000-IV or severe aGVHD-free survival (SGFS) to day 180+, and the rate of severe aGVHD until day 180+.

Results of 8 of the patients showed that grade 3/4 aGVHD was 6.8% with abatacept versus 14.8% with placebo (HR 0.45; 80% CI 0.22-0.90; p = 0.13 ). The combination of a calcineurin inhibitor and methotrexate-based GVHD prophylaxis with abatacept achieved an SGFS rate of 93.2% compared to 82% in the placebo arm (HR 0.37; 80% CI 0.19-0.73; p = 0.05).

In the smaller cohort of patients (n = 7/8), the incidence of aGVHD was 2.3% with the abatacept combination, comparing favorably with a non-randomized matched cohort containing a calcineurin inhibitor and methotrexate-based GVHD- received prophylaxis. The addition of abatacept also resulted in a better SGFS rate of 97.7% compared to 58.7% in the placebo arm (P < .001).

In this study, it was further shown that adding abatacept to a calcineurin inhibitor and methotrexate-based GVHD prophylaxis controlled T cell activation.

Abatacept is not yet approved for the treatment or prevention of any cancer. The drug has an indication for the treatment of arthritis. The abatacept label warns against using the drug with biologics and JAK inhibitors. The label also states that the most common side effects seen in more than 10% of patients treated are headache, upper respiratory tract infection, and nasopharyngitis.

“For patients receiving unrelated donor stem cell transplants, especially those from racial and ethnic minorities, there is an increased risk of developing aGvHD, a potentially life-threatening medical complication for which there are no approved preventive therapies,” says Mary Beth. Harler, MD, chief of Immunology and Fibrosis Development, Bristol Myers Squibb, in a press release. “We look forward to working with the FDA to bring Orencia to this new patient population and leverage cutting-edge science in an effort to address unmet needs of patients with inadequate care.”


1. The US Food and Drug Administration is accepting for priority review Bristol Myers Squibb’s application for Orencia (abatacept) for the prevention of acute graft-versus-host disease (aGVHD). news item. August 23, 2021. Accessed August 23, 2021.

2. Watkins B, Qayed M, McCracken C, et al. Phase II study of costimulation blockade with abatacept for prevention of acute GVHD. J Clin Oncol. 2021;39(17): 1865-1877. doi: 10.1200/JCO.20.01086

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