BMS Receives FDA Breakthrough Therapy Designation for Orencia (Abatacept) to Prevent Acute Graft-Versus-Host Disease

Today, Bristol-Myers Squibb (BMS) announced that the U.S. FDA has granted Breakthrough Therapy Designation to its drug Orencia (abatacept) for the prevention of moderate-to-severe acute graft-versus-host disease (GvHD) in patients undergoing hematopoietic stem cell transplantation from unrelated donors.

Stem cell transplantation has been proven to be an effective and often the only treatment for leukemia and other hematologic malignancies; however, certain benefits of this approach are offset by severe complications from graft-versus-host disease (GvHD). Forty percent of patients undergoing stem cell transplantation from unrelated donors develop GvHD due to human leukocyte antigen (HLA) mismatch. This life-threatening complication results from immune attacks by allogeneic transplanted stem cells against host organs, potentially impairing the function of multiple organ systems, including the skin, gastrointestinal tract, and liver. Organ damage caused by acute GvHD is closely associated with increased morbidity and mortality in patients. Currently, there are no approved therapies for the prevention of acute GvHD.

Orencia treats autoimmune diseases by interfering with the immune activity of T cells. Orencia is a fusion protein composed of the extracellular domain of CTLA-4 and the Fc region of immunoglobulin G1 (IgG1). For T cells to be activated and generate an immune response, antigen-presenting cells (APCs) must deliver two signals to the T cells. One signal is the major histocompatibility complex (MHC) combined with the antigen, and the other is the CD80/86 molecules. Orencia specifically and effectively binds to CD80/86 molecules, blocking the second signal, thereby preventing T cell activation. Previously, Orencia has been approved by the FDA for the treatment of adult patients with active psoriatic arthritis (PsA) and rheumatoid arthritis (RA), as well as adolescent patients with juvenile idiopathic arthritis (JIA).

▲Mechanism of Action of Orencia (Image source: Bristol-Myers Squibb official website)

This breakthrough therapy designation is based on the positive results of Orencia in a Phase 2 clinical trial, which aimed to evaluate the efficacy of adding Orencia to standard graft-versus-host disease (GvHD) prophylaxis regimens for the prevention of severe acute GvHD. This approach can be used to treat patients with hematologic malignancies who undergo stem cell transplantation from unrelated donors, regardless of HLA matching status.

“We are encouraged by the potential of Orencia to improve outcomes in patients undergoing stem cell transplantation from unrelated donors. Fully matched unrelated donor transplants are rarely achievable, and we believe these data have the potential to expand the donor pool for stem cell transplant recipients,” said Dr. Brian Gavin, Head of Orencia Development at Bristol-Myers Squibb. “We look forward to working with the FDA to make Orencia the first approved therapy for the prevention of acute GvHD.”

References:

[1] Bristol-Myers Squibb Announces U.S. FDA Breakthrough Therapy Designation for ORENCIA® (abatacept) to Help Prevent Acute Graft-Versus-Host Disease, a Potentially Life-Threatening Complication After Stem Cell Transplant，Retrieved December 04, 2019, from https://www.businesswire.com/news/home/20191204005265/en/Bristol-Myers-Squibb-Announces-U.S.-FDA-Breakthrough-Therapy

[2] Bristol-Myers Squibb Official Website，Retrieved December 04, 2019, from http://www.orenciahcp.com/role-of-t-cells-in-rheumatoid-arthritis

[3] Express | BMS Immunotherapy Drug Approved Today for the Treatment of Psoriatic Arthritis, Retrieved December 04, 2019, from https://mp.weixin.qq.com/s/K2G1PphH86ID01Zf_CVbXA

Original Title:Flash | BMS Immunomodulator Receives Breakthrough Therapy Designation for Treatment of Graft-versus-Host Disease

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