A Drug Receives FDA Approval for the First Time to Prevent Graft-Versus-Host Disease

A condition in which donor bone marrow or stem cells attack the recipient’s cells is acute graft-versus-host disease (aGVHD). For its prophylaxis (prevention), the drug with abatasept as its active ingredient, Orencia, was approved by the FDA (United States Food and Drug Administration) on 15 December 2021. Orencia can be used with certain immunosuppressive drugs in adults and pediatric patients aged two years or older undergoing hematopoietic stem cell transplantation (commonly known as bone marrow or stem cell transplantation) from an unrelated donor. 

This is the first approval for aGVHD prevention by the FDA for a drug, and it incorporates real-world evidence as a component of determining clinical effectiveness. Real-world evidence is clinical evidence about the use and potential benefits or risks of a medical product derived from analysis of real-world data, such as routinely collected information on patient health status and/or healthcare delivery from various sources, including electronic health records.

Previously, in 2017, ibrutinib received FDA approval for the “treatment” of GVHD.

Acute graft-versus-host disease can affect different parts of the body and occur as a complication after bone marrow/stem cell transplantation. By potentially preventing aGVHD, this drug could allow more patients to undergo successful bone marrow or stem cell transplantation with fewer complications.

Acute GVHD is a potentially fatal complication that can occur after stem cell transplantation when the donor’s immune cells (the graft) recognize the recipient’s body (the host) as foreign and the donated cells attack the body. The likelihood of developing aGVHD rises when the donor and recipient are unrelated or do not have a perfect tissue (HLA) match. 

The safety and effectiveness of Orencia in combination with immunosuppressive treatment were evaluated in two separate studies in patients aged six years or older undergoing stem cell transplantation from a matched or mismatched unrelated donor.

GVHD-1 was a double-blind, placebo-controlled clinical trial involving 186 patients undergoing stem cell transplantation from an unrelated donor. The study measured severe (grade III-IV) aGVHD-free survival, overall survival and moderate-to-severe (grade II-IV) aGVHD-free survival six months after transplantation.

• Severe aGVHD survival improved numerically in patients receiving Orencia compared with placebo: 75% versus 87%, respectively, although the difference was not statistically significant.
• However, the overall survival rate was 97% in patients receiving Orencia, compared with 84% in those receiving placebo.
• For moderate-to-severe aGVHD-free survival, Orencia patients had a rate of 50%, compared with 32% in placebo patients.

Additional evidence of effectiveness came from GVHD-2, a registry-based clinical study using real-world data from the Center for International Blood and Marrow Transplant Research in patients receiving stem cell transplants from a mismatched unrelated donor. The study analyzed outcomes for 54 patients treated with Orencia in combination with standard immunosuppressive drugs to prevent aGVHD versus 162 patients treated with standard immunosuppressive drugs alone. It measured overall survival six months after transplantation. Patients receiving Orencia had an overall survival advantage compared with those receiving only standard immunosuppression: 98% versus 75%.

The most common side effects of Orencia for preventing aGVHD include anemia, hypertension, cytomegalovirus (CMV) reactivation/CMV infection, fever, pneumonia, nosebleeds, reduced levels of specific white blood cells called CD4 lymphocytes, increased blood magnesium levels and acute kidney injury.

Patients receiving Orencia should be monitored for Epstein-Barr virus reactivation according to institutional practices and receive preventive medication for Epstein-Barr virus infection before starting treatment and for six months after transplantation. Patients should also be monitored for CMV infection/reactivation for six months after transplantation. 

Orencia was first approved by the FDA in 2005 to treat adult rheumatoid arthritis. Orencia is also approved for polyarticular juvenile idiopathic arthritis and adult psoriatic arthritis. Orencia is also authorized by the Ministry of Health in Turkey for these two indications.  

The FDA granted approval of Orencia to Bristol Myers Squibb.