FDA Approves Abatacept With Calcineurin Inhibitor for Prophylaxis of Acute Graft Versus Host Disease

Abatacept is also approved for adults with moderate to severe rheumatoid arthritis, active psoriatic arthritis, and moderate to severe polyarticular juvenile idiopathic arthritis for children 2 years of age and older.

The FDA approved abatacept (Orencia; Bristol Myers Squibb) for the prophylaxis, or prevention, of acute graft versus host disease (aGVHD) in combination with a calcineurin inhibitor and methotrexate for individuals 2 years of age or older undergoing hematopoietic stem cell transplantation (HSCT) from a matched or 1 allele-mismatched unrelated donor.

“Orencia is the first FDA-approved therapy to prevent aGVHD following hematopoietic stem cell transplant, a potentially life-threatening complication that can pose a comparatively higher risk to racial and ethnic minority populations in the US due to difficulty finding appropriately matched donors,” said Tina Deignan, PhD, senior vice president of US Immunology at Bristol Myers Squibb, in a press release.

Allogeneic HSCT is a treatment for hematological diseases that involves the infusion of hematopoietic stem cells, which includes donor T-cells, a type of white blood cell that recognizes and destroys foreign invaders and damaged or cancerous cells in the body.

The aGVHD occurs when the donor T-cells recognize an individual’s healthy cells and begins attacking healthy tissues and organs.

Abatacept binds to and modulates protein targets involved in costimulation, which would inhibit T-cell activation. There is no known relationship between these biological response markers to the mechanisms by abatacept’s clinical effects.

Abatacept has other indications for adults with moderate to severe rheumatoid arthritis, active psoriatic arthritis, and moderate to severe polyarticular juvenile idiopathic arthritis for children 2 years of age and older.

The approval is based on results from the phase 2 GVHD-1 trial, also known as ABA2, that evaluated abatacept when added to a regimen of a calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate for prophylaxis of aGVHD in individuals undergoing HSCT, and a clinical study known as GVHD-2 using data from the Center for International Blood and Marrow Transplant Research.

“The findings suggest abatacept could play an important role in preventing aGVHD in hematopoietic stem cell transplant,” said Leslie Kean, MD, director of the Stem Cell Transplantation Center at Dana-Farber/Boston Children's Cancer and Blood Disorders Center, in the press release. “From these results, providers may also have more confidence in expanding the donor pool to include unrelated matched or 1 allele-mismatched donors for patients in need.”

The concomitant use of abatacept with other immunosuppressives is not recommended. Abatacept has been associated with an increased risk of infection with concomitant use with tumor necrosis factor antagonists, other biologic rheumatoid arthritis and psoriatic arthritis therapy, or Janus kinase inhibitors; hypersensitivity; increased risk of serious infections; interactions with immunizations; and increased risk of adverse events (AEs) when used in patients with chronic obstructive pulmonary disease.

The most common AEs in rheumatoid arthritis are headache, nasopharyngitis, nausea, and upper respiratory tract infection. Common AEs for prophylaxis of aGVHD are acute kidney injury, anemia, cytomegalovirus (CMV) reactivation/CMV infection, hypertension, hypermagnesemia, pneumonia, and pyrexia.

Reference

US Food and Drug Administration approves Orencia (abatacept) in combination with a calcineurin inhibitor and methotrexate for the prevention of acute graft versus host disease (aGvHD). Businesswire. News release. December 15, 2021. Accessed December 16, 2021. https://www.businesswire.com/news/home/20211213006061/en