The Food and Drug Administration has accepted for Priority Review the supplemental Biologics License Application for abatacept (Orencia) for the prevention of moderate to severe acute graft versus host disease (aGvHD) in patients 6 years of age and older receiving unrelated donor hematopoietic stem cell transplantation.
The application is supported by data from the multicenter, randomized, double-blind, placebo-controlled phase 2 ABA2 trial (ClinicalTrials.gov Identifier: NCT01743131) and real world evidence from a registry trial. The ABA2 trial evaluated abatacept, a selective T-cell costimulation modulator, for the prevention of severe aGvHD when added to a standard GvHD prophylactic regimen in patients with hematologic malignancies receiving a stem cell transplant from an unrelated, human leukocyte antigens (HLA)-matched or mismatched donor.
The ABA2 trial included 2 cohorts: a single arm cohort for patients receiving transplants from HLA-mismatched unrelated donors (“7/8″ cohort), and a randomized, double-blind, placebo-controlled cohort for patients receiving transplants from 8/8 HLA-matched unrelated donors (“8/8” cohort). All patients received a calcineurin inhibitor and methotrexate. Patients treated with abatacept received abatacept 10mg/kg administered via intravenous infusion on days -1, 5, 14, and 28, with day 0 indicating day of transplant.
Findings showed that the addition of abatacept achieved a significantly higher aGvHD-free survival rate compared with patients from the registry in the 7/8 cohort. Moreover, the addition of abatacept had a numerically higher severe aGvHD-free survival rate in the 8/8 cohort at 180 days post-transplant. These results were consistent with that observed in the real world analysis from the registry trial.
A Prescription Drug User Fee Act target date of December 23, 2021 has been set for this application.
“While stem cell transplants are an effective treatment for aggressive leukemias and other hematological malignancies, patients who receive stem cell transplants from unrelated and HLA-mismatched donors are at high risk for developing aGvHD,” said study lead investigator Leslie Kean, MD, PhD, Director of the Pediatric Stem Cell Transplantation Program, Boston Children’s Hospital/Dana-Farber Cancer Institute. “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 is marketed under the trade name Orencia and is currently indicated for the treatment of adults with moderately to severely active rheumatoid arthritis and adults with active psoriatic arthritis. It is also approved for the treatment of patients 2 years of age and older with moderate to severely active polyarticular juvenile idiopathic arthritis.
US 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. Accessed August 23, 2021. https://www.businesswire.com/news/home/20210823005092/en/U.S.-Food-and-Drug-Administration-Accepts-for-Priority-Review-Bristol-Myers-Squibb%E2%80%99s-Application-for-Orencia-abatacept-for-the-Prevention-of-Acute-Graft-Versus-Host-Disease-aGvHD.