Priority Review for Abatacept BLA Granted by the FDA for GVHD Prophylaxis

Priority review for a biologics license application for prophylactic abatacept has been granted by the FDA to help prevent the occurrence of severe graft-versus-host disease for patients undergoing hematopoietic stem cell transplant from an unrelated donor.

The FDA has accepted and granted priority review to a supplemental biologics license application for abatacept (Orencia) to prevent moderate-to-severe acute graft-versus-host disease (GVHD) in patients who are 6 years of age or older and are being treated with unrelated donor hematopoietic stem cell transplant (HSCT), according to the company responsible for the agent’s development, Bristol Myers Squibb.1

The submission was based on the results of the double-blind, placebo-controlled, randomized phase 2 ABA2 study (NCT01743131), as well as a real-world registry trial.2 Findings from ABA2 indicated that the incidence of grade 3/4 acute GVHD in a cohort of patients receiving HSCT from 8/8-matched unrelated donors was 6.8% among those who received abatacept compared with 14.8% in the placebo cohort (HR, 0.45; P = .13). Moreover, the severe acute GVHD–free survival (SGFS) for those who received a calcineurin inhibitor (CNI) and methotrexate–based prophylaxis plus abatacept was 93.2% compared with 82% in the placebo arm (P = .05).

Notably, the application was given a Prescription Drug User Fee Act goal date of December 23, 2021.

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

Abatacept has previously been approved to treat a number of arthritic conditions by binding to and inhibiting protein targets that are involved in co-stimulation, leading to T-cell activation. The multicenter ABA2 trial assessed the efficacy of abatacept in preventing severe acute GVHD when added to a standard prophylactic regimen in a population of patients with hematologic malignancies who were treated with HSCT from an unrelated HLA-matched or -mismatched donor.

The study included 142 and 43 recipients in the 8/8 and 7/8 cohorts, respectively. All patients enrolled in the study received a CNI on day 2 and continued through day 100 depending on tolerance, and methotrexate was administered on days 1, 3, 6, and 11. Those in the abatacept cohort were given the agent at a dose of 10 mg/kg on days -1, 5, 14, and 28.

Additional findings from the study indicated that in a smaller single-arm cohort of patients who received 7/8 HSCT from mismatched unrelated donors, the incidence of GVHD was 2.3% in the abatacept arm and 30.2% in a nonrandomized matched cohort of CNI/methotrexate (P <.001). The cohort also saw an improvement in SGFS between the 2 arms (97.7% vs 58.7%; P <.001).

“For patients who receive unrelated donor stem cell transplants, in particular for racial and ethnic minority patient populations, there is a heightened risk of developing [acute] GvHD, a potentially life-threatening medical complication for which there are no approved preventive therapies. We look forward to working with the FDA to bring Orencia to this new patient population and employ pathbreaking science in an effort to address unmet needs of underserved patients,” Mary Beth Harler, MD, head of Immunology and Fibrosis Development at Bristol Myers Squibb, concluded.


  1. U.S. Food and Drug Administration accepts for priority review Bristol Myers Squibb’s application for Orencia (abatacept) for the prevention of acute graft versus host disease (aGvHD). News release. Bristol Myers Squibb. August 23, 2021. Accessed August 23, 2021.
  2. Watkins B, Qayed M, McCracken C, et al. Phase II Trial of Costimulation Blockade With Abatacept for Prevention of Acute GVHD. J Clin Oncol. 2021;39(17):1865-1877. doi:10.1200/JCO.20.01086