FDA Grants Breakthrough Designation to Abatacept for Prevention of Acute GVHD

December 4, 2019
Nichole Tucker

Nichole Tucker, MA, is the Web Editor for Targeted Oncology. Tucker received her Bachelor of Arts in Mass Communications from Virginia State University and her Master of Arts in Media & International Conflict from University College Dublin.

Abatacept has been granted a Breakthrough Therapy Designation by the FDA for the prevention of moderate to severe acute graft-versus-host disease in hematopoietic stem cell transplants from unrelated donors.

Abatacept (Orencia) has been granted a Breakthrough Therapy Designation by the FDA for the prevention of moderate to severe acute graft-versus-host disease (GVHD) in hematopoietic stem cell transplants (SCTs) from unrelated donors.

The designation was based on data from a phase II ABA2 trial, in which abatacept was added to the standard GVHD prophylactic regimen given to patients with hematologic malignancies who were to receive a SCT from an unrelated donor, which increases the risk of GVHD in these patients. ABA2 is a two-arm trial of either abatacept added to calcineurin inhibitor and methotrexate and placebo or calcineurin inhibitor and methotrexate and placebo only.

According to the results of the ABA2 trial, abatacept reduced the developed of all-grade acute GVHD (aGVHD). In the group of patients receiving donations with a mismatched human leukocyte antigens (HLA) gene treated with abatacept, only 2.5% developed grade 3 or 4 aGVHD (n = 1) versus 31% in patients treated with a calcineurin inhibitor and methotrexate (CNI + MTX) only and 22% in the arm that also received anti-thymocyte globulin (ATG) placebo with CNI + MTX.

Grade 2 through 4 aGVHD were higher in both arms. Specifically, aGVHD occurred in 42% of patients in the abatacept group versus 54% in those treated with CNI + MTX and 45% in the participants treated with ATG.

The was no increase in relapse with abatacept. Less than 10% of patients in the abatacept group (9.37%) relapsed at 1 year. Individuals who received SoC relapsed at a higher rate than those treated with abatacept (13.8%). However, the highest percentage of relapse was observed in the placebo group (20.5%) (P= 0.7). No further relapses were reported in the ABA2 study.

Abatacept also demonstrated a statistically significant increase in OS compared to both SoC and placebo. The OS rate was 71% with abatacept vs. 47.5% with CNI + MTX and 26% when ATG was added to treatment. A relapse-free survival benefit was seen with abatacept above both the CNI + MTX and ATG arms, which was 71%, 47.5%, and 58%, respectively.

The study investigators concluded that these data indicate the potential for abatacept to prevent aGVHD without compromising safety or cause of relapse.

“While ideally, we prefer using fully matched transplants from a sibling for the treatment of hematologic cancers, only the minority of patients have such a sibling,” said study lead investigator Leslie Kean, MD, director of the Stem Cell Transplantation Program, Dana Farber Cancer Institute and Boston Children’s Cancer and Blood Disorders Center, in the press release, “a therapy that lowers the risk of GVHD in unrelated stem cell transplants would potentially allow more patients to receive a transplant, which typically is the last option to treat hematologic cancers after other therapies have been used unsuccessfully.”

The phase II ABA2 trial is an ongoing multicenter, randomized double-blind, placebo-controlled study. In comparator arm A, patients received CNI + MTX and ATG, and in comparator arm B abatacept is added to CNI + MTX and ATG. The primary endpoint of the study is the cumulative incidence of severe aGVHD at day +100 post-transplant. The secondary endpoints are a cumulative incidence of serious infection, engraftment, relapse, and overall survival (OS), relapse-free survival (RFS), and a comparison of the cumulative incidence of severe (grade 3 through 4) aGVHD up to Day +180, which is based on adjudicated aGVHD events.

Individuals were required to have a high-risk hematologic malignancy and be at least 6 years of age to enroll in the study. The study excluded individuals who had prior allogeneic hematopoietic stem cell transplantation, and those with uncontrolled viral, bacterial, fungal or protozoal infections, HIV infection, and serious psychiatric disease.

Bristol-Myers Squibb anticipates that abatacept will become the first approved therapy for the prevention of GVHD and plans on working with the FDA.

“We are excited about the potential of ORENCIA to improve outcomes for patients receiving unrelated stem cell transplants. We believe the data could lead to an expansion of the donor pool for stem cell transplants in some patient populations were fully matched unrelated donor transplants have rarely been available. We look forward to working with the FDA and making ORENCIA the first approved therapy for the prevention of acute GVHD,” Brian Gavin, PhD, development lead, ORENCIA, Bristol-Myers Squibb, noted in a statement.


  1. Bristol-Myers Squibb Announces U.S. FDA Breakthrough Therapy Designation for ORENCIA® (abatacept) to Help Prevent Acute Graft-Versus-Host Disease, a Potentially Life-Threatening Complication After Stem Cell Transplant [press release]. Princeton, NJ: Bristol-Myers Squibb; December 4, 2019.https://bit.ly/2DJe2QV. Accessed December 4, 2019.
  2. Watkins BK, Qayed M, Bratrude B, et al. T Cell Costimulation Blockade with CTLA4-Ig (Abatacept) for Acute Gvhd Prevention in HLA Matched and Mismatched Unrelated Donor Transplantation: Results of the First Phase 2 Trial. Presented at the 2019 Transplantation & Cellular Therapies Meeting, February 20—24 in Houston Texas. Abstract 65.