The FDA has accepted the supplemental biologics license application for abatacept and granted it priority review for the prevention of moderate to severe acute graft versus host disease in patients 6 years of age and older receiving unrelated donor hematopoietic stem cell transplantation.
The FDA has accepted the supplemental biologics license application (BLA) for abatacept (Orencia) and granted it priority review 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 (HSCT), announced Bristol Myers Squibb, in a press release.1
The application has been assigned a Prescription Drug User Fee Act target action 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 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, 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 trial, 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 along with significantly improving aGVHD-related transplant outcomes. Data from the ABA2 trial support the BLA.1,2
Approximately 186 adult and pediatric patients with hematologic malignancies under 2 strata were included in the multicenter, randomized, double-blind, placebo-controlled trial. Patients were randomized to receive either standard GVHD prophylaxis with placebo or standard GVHD prophylaxis with abatacept. The primary end point assessed in the study was the percentage of patients with a cumulative incidence of severe aGVHD at day 100+ post-transplant.2
The secondary end points of the study include the cumulative incidence of serious infection, engraftment, relapse, and overall survival, as well as the percentage of patients with grade 000-IV or severe aGVHD free survival (SGFS) up to day 180+, and the rate of severe aGVHD up to day 180+.
Results from 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 =.13). The combination of a calcineurin inhibitor and methotrexate-based GVHD prophylaxis with abatacept achieved an SGFS rate of 93.2% compared with 82% in the placebo arm (HR, 0.37; 80% CI, 0.19-0.73; P =.05).
In the smaller cohort of patients (n = 7/8), the incidence of aGVHD was 2.3% with the abatacept combination, which showed a favorable comparison to a no nonrandomized matched cohort that received a calcineurin inhibitor and methotrexate-based GVHD prophylaxis. The addition of abatacept also led to a better SGFS rate of 97.7% compared with 58.7% in the placebo arm (P <.001).
It was further shown in this study 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 form of cancer. The drug has an indication for arthritis treatment. The label for abatacept warns against using the agent with biological agents and JAK inhibitors. The label also mentions that the most frequent adverse events observed in more than 10% of patients who have been treated include headache, upper respiratory tract infection, nasopharyngitis.
“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 aGvHD, a potentially life-threatening medical complication for which there are no approved preventive therapies,” said Mary Beth Harler, MD, head 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 employ pathbreaking science in an effort to address unmet needs of underserved patients.”
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. 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