Bristol Myers Squibb has announced that the US Food and Drug Administration (FDA) has accepted its supplemental Biologics License Application (sBLA) for Orencia (abatacept) for the prevention of moderate-to-severe acute graft versus host disease (aGvHD) in patients six years of age and older receiving unrelated donor hematopoietic stem cell transplantation (HSCT). The FDA granted the application Priority Review and assigned a Prescription Drug User Fee Act (PDUFA) goal date of 23rd December, 2021, a company statement said.
“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, Pediatric Stem Cell Transplantation Program, Boston Children’s Hospital/Dana-Farber Cancer Institute.
She added, “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.”
The statement also said that stem cell transplants include infusion of donor T-cells, a type of white blood cell that recognises and destroys foreign invaders in the recipient’s body, including cancer cells. GvHD occurs when the donor T-cells also recognise the patient’s healthy cells as foreign and start attacking healthy tissues and organs. To initiate this attack, T-cells require activation through a signaling process called co-stimulation. Between 30 and 70 per cent of transplant recipients develop aGvHD, depending on donor type, transplant technique and other features. Orencia, a therapy currently approved to treat various arthritic conditions, binds to and inhibits protein targets involved in co-stimulation, thus inhibiting T-cell activation.
“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.
She further added, “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.”
The sBLA submitted to the FDA is based on results from the phase-II ABA2 trial and a registry trial based on real-world evidence. The ABA2 trial assessed the impact of Orencia on the prevention of severe aGvHD, when added to a standard GvHD prophylactic regimen administered to patients with hematologic malignancies receiving a stem cell transplant from an unrelated, HLA-matched or mismatched donor. A mismatch in HLA increases the risk of GvHD. Results from ABA2 showed that treatment with Orencia resulted in a significant reduction in severe aGvHD and associated morbidity without an increase in disease relapse. The findings of the real-world analysis were consistent with those of ABA2, mentioned the statement.