The US Food and Drug Administration has accepted a supplemental biologics licence application for Bristol Myers Squibb’s Orencia (abatacept) for the prevention of moderate-to-severe acute graft versus host disease (aGvHD) in patients receiving a stem cell transplant from an unrelated donor.
“While stem cell transplants are an effective treatment for aggressive leukaemias and other haematological 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, director of the paediatric stem cell transplantation programme at 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.”
In GvHD, transplanted donor T-cells are triggered by antigenic differences between donor and host causing them to attack the recipient’s healthy tissue and organs. The activated T-cells commonly target the host’s skin, liver and gastrointestinal tract, where damage has been associated with increased morbidity and death.
The acute disease (aGvHD) impacts 30-70% of patients, with racial and ethnic minority patients “more likely to experience challenges” following a hematopoietic stem cell transplantation, says Bristol Myers Squibb (BMS).
Orencia is an immunomodulator that disrupts the continuous cycle of T-cell activation. It is already indicated in the US for rheumatoid and psoriatic arthritis in adults and polyarticular juvenile idiopathic arthritis.
In aGVHD, T-cells are activated through a signalling process called co-stimulation. Orencia binds to and inhibits protein targets involved in co-stimulation, thus inhibiting T-cell activation and the damage to healthy organs.
“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, head of immunology and fibrosis development at BMS. “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.”
In accepting the priority review, the FDA assigned an action date of 23 December.