FDA Grants Orencia (abatacept) Breakthrough Therapy Designation for Severe Acute Graft-Versus-Host Disease (GvHD)

Dec 7, 2019 | Graft-Versus-Host Disease (GvHD), hematologic cancers, Stem Cell Transplantation, Transplantation

FDA Grants Orencia (abatacept) Breakthrough Therapy Designation for Severe Acute Graft-Versus Host Disease GvHD)

Bristol-Myers Squibb (BMS) secured breakthrough therapy status from the Food and Drug Administration (FDA) for Orencia (abatacept) to prevent moderate to severe acute graft-versus host disease (GvHD) in hematopoietic stem cell transplants from unrelated donors.

What is GvHD?

A potentially life-threatening medical complication that can affect patients receiving transplants to treat certain genetic diseases and hematologic cancers. It follows from the receipt of transplanted tissue from a genetically different person. It is commonly associated with stem cell transplants such as those that occur with bone marrow transplants. It can apply to other forms of transplanted tissues such as solid organ transplants.

White blood cells of the donor’s immune system, which remain within the donated tissue (the graft), recognize the recipient (the host) as foreign (non self). The white blood cells present within the transplanted tissue then attack the recipient’s body’s cells, which leads to GvHD. This is different than a transplant rejection, which occurs when the immune system of the transplant recipient rejects the transplanted tissue. So GvHD actually occurs when the donor’s immune system’s white blood cells reject the recipient. This underlying principal (alloimmunity) is the same, but the details and course of action may differ. GvHD can also occur after a blood transfusion if the blood products used have not been irradiated or treated with an approved pathogen reduction system.

What is Orencia?

An immunomodulator that disturbs the continuous cycle of T-cell activation, which indicates rheumatoid arthritis (RA). 

The recent FDA designation was based on the results from an investigator-initiated trial supported by Bristol-Myers Squibb. As reported in Yahoo Finance, the drug is approved in the United States and indicated for reducing signs and symptoms, inducing major clinical response, inhibiting the progression of structural damage, and improving physical function in adult patients with moderately to severely active rheumatoid arthritis. It is used for the treatment of adults with active psoriatic arthritis. Orencia became the first biologic therapy to gain EU approval specifically for the treatment of methotrexate (MTX)-naïve RA patients with highly active and progressive disease. The drug’s label was expanded in Europe to include psoriatic arthritis as well. 

The ABA2 Study

A Phase II study (ABA2 Trial), the team evaluated the impact of Orencia on the prevention of severe acute GvHD, when combined with a standard GvHD prophylactic regimen given to patients with hematologic malignancies who were to receive SCT from an unrelated donor, hence increasing the risk of GvHD in these patients. A multi-center, randomized, double blind, placebo-controlled trial, the investigators conducted this study to determine if abatacept can be used together with a calcineurin inhibitor (cyclosporine or tacrolimus) and methotrexate to offer improved protect against acute GvHD without triggering more infections.

Research Centers

Research sites associated with ABA2 include: Children’s Hospital, Los Angeles; UCSF Benioff Children’s Hospital, Oakland; Children’s Hospital Colorado, Aurora; Children’s National Medical Center, Washington, DC; University of Florida, Gainesville; Children’s Healthcare of Atlanta at Egleston, Atlanta; Emory University/Winship Cancer Center, Atlanta; Dana-Farber Cancer Institute, Boston; University of Michigan, Ann Arbor; Washington University St. Louis; Michael Grimley, Cincinnati; University of Utah, Salt Lake City; Seattle Cancer Care Alliance, Seattle and Children’s and Women’s Health Center of BC, Vancouver. Boston Children’s Hospital’s Leslie Kean, MD, PhD, leads this study effort.


The ABA2 trial revealed that abatacept reduced the development of all-grade acute GvHD. For example in the abatacept only group, only 2.5% developed grade 3 or 4 aGvHD versus 31% in patients treated with calcineurin inhibitor and methotrexate only and 22% in the arm that also received anti-thymocyte globulin (ATG) placebo with abatacept and the calcineurin inhibitor and methotrexate combination. Grade 2 to 4 aGvHD increased in both arms—aGvHD occurred in 42% of patients in the abatacept group versus 54% in those treated with calcineurin inhibitor and methotrexate combination and 45% in the participants with ATG.

As reported in Targeted Oncology, principal investigator Leslie Kean, MD, director of the Stem Cell Transplantation Program, Dana-Farber Cancer Institute and Boston Children’s Cancer and Blood Disorders Center, stated, “While ideally, we prefer using fully matched transplants from a sibling for the treatment of hematologic cancers, only the minority of patients have such a sibling.” Dr. Kean continued, “A therapy that lowers the risk of GvHD in unrelated stem cell transplants would potentially allow more patients to receive a transplant, which typically is the last option to treat hematologic cancers after other therapies have been used unsuccessfully.

Lead Research/Investigator

Leslie Kean, MD, director of the Stem Cell Transplantation Program, Dana-Farber Cancer Institute and Boston Children’s Cancer and Blood Disorders Center


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