On December 15, 2021, the Food and Drug Administration approved abatacept (Orencia, Bristol-Myers Squibb Company) for the prophylaxis of acute graft versus host disease (aGVHD), in combination with a calcineurin inhibitor (CNI) and methotrexate (MTX), in adults and pediatric patients 2 years of age and older undergoing hematopoietic stem cell transplantation (HSCT) from a matched or 1 allele-mismatched unrelated donor. This is the first drug approved to prevent aGVHD. The application included use of real world data (RWD) in the determination of clinical effectiveness. RWD is clinical data routinely collected from a variety of sources, including registry data, to generate real world evidence (RWE).  

Efficacy was evaluated in two studies in patients six years and older undergoing HSCT from a matched or 1 allele-mismatched unrelated donor.  

GVHD-1 (NCT 01743131) was a randomized (1:1), double-blind, placebo-controlled clinical trial of patients who underwent an 8 of 8 Human Leukocyte Antigen (HLA)-matched HSCT and received abatacept or placebo in combination with a CNI and MTX. While severe (grade III-IV) aGVHD-free-survival assessed at Day 180 after transplantation was not significantly improved in patients who received Orencia compared to patients who received a placebo (HR 0.55; 95% CI 0.26, 1.18), the OS rate at Day 180 after HSCT was 97% (95% CI: 89%, 99%) for patients who received abatacept compared to 84% (95% CI: 73%, 91%) for patients who received a placebo (HR 0.33; 95% CI: 0.12, 0.93). The moderate-severe (grade II-IV) aGVHD-free survival rate at Day 180 after HSCT was 50% (95% CI: 38%, 61%) for patients who received abatacept compared to 32% (95% CI: 21%, 43%) for patients who received a placebo (HR 0.54; 95% CI: 0.35, 0.83).  

Additional evidence of effectiveness was provided by GVHD-2, a clinical study using data from the Center for International Blood and Marrow Transplant Research (CIBMTR) in patients who underwent a 7 of 8 HLA-matched HSCT between 2011 and 2018. This registry-based study analyzed outcomes of 54 patients treated with abatacept for the prophylaxis of aGVHD, in combination with a CNI and MTX, versus 162 patients randomly selected from the CIBMTR registry treated with a CNI and MTX alone. The OS rate at Day 180 after HSCT was 98% (95% CI: 78%, 100%) for patients who received abatacept in combination with CNI and MTX compared to 75% (95% CI: 67%, 82%) for patients who received CNI and MTX alone. 

The most common adverse reactions (≥10%) of abatacept for the prophylaxis of aGVHD are anemia, hypertension, CMV reactivation/CMV infection, pyrexia, pneumonia, epistaxis, CD4 lymphocytes decreased, hypermagnesemia and acute kidney injury. Patients who receive abatacept should receive antiviral prophylaxis for Epstein-Barr virus infection before starting treatment and for six months post-transplantation and be monitored for cytomegalovirus infection/reactivation for six months post-transplant. 

The recommended abatacept dose depends upon the age of the patient and is described in prescribing information. View full prescribing information for Orencia

This review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with Health Canada, Switzerland’s Swissmedic, and Israel’s Ministry of Health. The application reviews are ongoing at the other regulatory agencies.  

This review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.  

This application was granted priority review, breakthrough designation and orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.

For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email [email protected]

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