Abatacept is approved for prophylaxis of acute graft versus host disease

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.

Nishant Mittal (PhD)

+ postsBio ⮌

Dr. Nishant Mittal is a highly accomplished researcher with over 13 years of experience in the fields of cardiovascular biology and cancer research. His career is marked by significant contributions to stem cell biology, developmental biology, and innovative research techniques.

Research Highlights

Dr. Mittal's research has focused on several key areas:

1) Cardiovascular Development and Regeneration: He studied coronary vessel development and regeneration using zebrafish models1.

2) Cancer Biology: At Dartmouth College, he developed zebrafish models for studying tumor heterogeneity and clonal evolution in pancreatic cancer.
3) Developmental Biology: His doctoral work at Keio University involved identifying and characterizing medaka fish mutants with cardiovascular defects.

4) Stem Cell Research: He investigated the effects of folic acid on mouse embryonic stem cells and worked on cryopreservation techniques for hematopoietic stem cells.

Publications and Presentations

Dr. Mittal has authored several peer-reviewed publications in reputable journals such as Scientific Reports, Cardiovascular Research, and Disease Models & Mechanisms1. He has also presented his research at numerous international conferences, including the Stanford-Weill Cornell Cardiovascular Research Symposium and the Weinstein Cardiovascular Development Conference.

In summary, Dr. Nishant Mittal is a dedicated and accomplished researcher with a strong track record in cardiovascular and cancer biology, demonstrating expertise in various model systems and a commitment to advancing scientific knowledge through innovative research approaches.

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