BMS’ Drug Wins First-In-Class Approval for Prevention of Acute Graft-Versus-Host Disease

The U.S. Food and Drug Administration (FDA) has granted approval to Bristol-Myers Squibb’s Orencia (abatacept) for the prevention of acute Graft-Versus-Host Disease (aGVHD) after bone marrow transplants. Orencia has previously been approved for use in the treatment of rheumatoid arthritis and psoriatic arthritis in adults and for polyarticular idiopathic arthritis in juveniles, the press release said. 

What is Acute GVHD?

It is a complication that can occur in individuals receiving hematopoietic stem cell transplants from donors who are not related or aren’t a perfect match. In this condition, the immune cells from the donor (the graft) recognize the recipient (host’s) body as foreign and launch an attack. According to Cleveland Clinic, aGVHD can occur within weeks after the transplant and commonly observed symptoms include rashes on the skin, yellowing of the eyes, nausea, vomiting, or abdominal cramping. 

To prevent this, clinicians often use immunosuppressive drugs after the transplant and the Orencia approval for prevention of aGVHD is in combination with these immunosuppressants. The approval follows the double-blind placebo-controlled study conducted in 186 patients who underwent allogeneic transplants – from donors who were not perfect matches. Patients were randomized to receive Orencia or a placebo in combination with immunosuppressive drugs. The study measured several outcomes such as overall survival, moderate-severe aGVHD-free, and severe GVHD-free survival six months after the transplant. 

Data from Clinical Trials

Patients who received Orencia saw a 97% overall survival rate as against 84% in those who received the placebo. While the drug’s impact on severe aGVHD survival was not statistically significant, patients who received the drug saw 50% moderate-severe aGVHD-free survival as compared to the 32% patients who received the placebo, said BMS.

A registry-based study conducted using real-world data further confirmed the findings. In 54 patients that received Orencia in combination with the immunosuppressive drugs at the Center for International Blood and Marrow Transplant Research in Wisconsin, overall survival six months after the transplant was 98 percent as against the 75 percent seen in 162 patients that received the immunosuppressive drugs alone. 

Side effects commonly seen with the use of Orencia included anemia, hypertension, fever, pneumonia, nosebleed, decreased counts of CD4 lymphocytes, increased magnesium levels in the blood, and acute kidney injury. Patients receiving Orencia also need to be monitored for cytomegalovirus infection or reactivation as well as Epstein-Barr Virus reactivation following the transplant, said BMS. 

This is the first FDA-approved drug for the prevention of aGVHD. The development of Orencia has been supported by the FDA’s Orphan Products Grants Program and has also received a Priority Review designation. The FDA’s review is part of Project Orbis that allows concurrent submission for regulatory approval in different countries. Orencia is also being reviewed by Health Canada, Swissmedic, and Israel’s Ministry of Health.

Author

Ameya Paleja