March 2022: Abatacept (Orencia, Bristol-Myers Squibb Company) has been approved by the Food and Drug Administration for the prevention of acute graft versus host disease (aGVHD) in adults and paediatric patients 2 years of age and older who are receiving hematopoietic stem cell transplantation (HSCT) from a matched or 1 allele-mismatched unrelated donor. This is the first treatment for aGVHD that has been approved by the FDA. Real-world data (RWD) was used in the application to determine clinical effectiveness. RWD refers to clinical data that is systematically collected from many sources, including registry data, in order to provide real-world evidence (RWE).
In two investigations, children aged six and up who received HSCT from a matched or 1 allele-mismatched unrelated donor were examined for efficacy.
GVHD-1 (NCT 01743131) was a randomised (1:1), double-blind, placebo-controlled clinical trial in which patients received abatacept or placebo in combination with a CNI and MTX after receiving an 8 of 8 Human Leukocyte Antigen (HLA)-matched HSCT. While severe (grade III-IV) aGVHD-free survival was not significantly improved in patients who received Orencia compared to patients who received a placebo at Day 180 after transplantation (HR 0.55; 95 percent CI 0.26, 1.18), the OS rate at Day 180 after HSCT was 97 percent (95 percent CI: 89 percent, 99 percent) for patients who received abatacept compared to 84 percent (95 percent CI: 73 percent, 91 percent) for patients (HR 0.33; 95 percent CI: 0.12, 0.93). At Day 180 after HSCT, the rate of moderate-severe (grade II-IV) aGVHD-free survival for patients who got abatacept was 50% (95 percent CI: 38 percent, 61 percent), compared to 32% (95 percent CI: 21 percent, 43 percent) for patients who received a placebo (HR 0.54; 95 percent CI: 0.35, 0.83).
GVHD-2, a clinical analysis based on data from the Center for International Blood and Marrow Transplant Research (CIBMTR) in patients who received a 7 of 8 HLA-matched HSCT between 2011 and 2018, revealed more evidence of effectiveness. The results of 54 patients treated with abatacept in conjunction with a CNI and MTX for the prevention of aGVHD were compared to 162 patients randomly selected from the CIBMTR registry who were treated with a CNI and MTX alone. Patients who got abatacept in combination with CNI and MTX had a 98 percent (95 percent CI: 78 percent, 100 percent) OS rate at Day 180 after HSCT, compared to 75 percent (95 percent CI: 67 percent, 82 percent) for patients who received CNI and MTX alone.
Anemia, hypertension, CMV reactivation/CMV infection, pyrexia, pneumonia, epistaxis, reduced CD4 cells, hypermagnesemia, and acute kidney injury are the most common side events (ten percent) of abatacept for the prevention of aGVHD. Patients receiving abatacept should be given antiviral prophylaxis for Epstein-Barr virus infection before starting treatment and for six months afterward, as well as be monitored for cytomegalovirus infection/reactivation.
The suggested abatacept dose is determined on the patient’s age and is listed in the prescribing material. Orencia prescription information is available in its entirety.
Project Orbis, an FDA Oncology Center of Excellence effort, was used to perform this review. Project Orbis creates a mechanism for worldwide partners to submit and review oncology medications at the same time. FDA worked on this review with Health Canada, Swissmedic, and Israel’s Ministry of Health. The other regulatory bodies are still reviewing the applications.