Bristol-Myers Squibb Company (NYSE: BMY) today announced that the U.S. Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation for ORENCIA® (abatacept) for the prevention of moderate to severe acute graft-versus-host disease (GvHD) in hematopoietic stem cell transplants from unrelated donors. There are no approved therapies for the prevention of acute GvHD, a potentially life-threatening medical complication that can impact patients receiving such transplants for the treatment of certain genetic diseases and hematologic cancers.1

Stem cell transplants have been shown to be an effective treatment for aggressive leukemias and other hematological malignancies, often representing the only therapeutic option for cure. However, some of their benefit is offset by the occurrence of severe acute GvHD, which impacts up to 40 percent of patients receiving stem cell transplants from unrelated donors with a mismatch in genes called human leukocyte antigens (HLA).2 These transplants are associated with a high rate of transplant-related mortality stemming largely from severe acute GvHD.3,4,5

“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,” said study lead investigator Leslie Kean, M.D., Director of the Stem Cell Transplantation Program, Dana Farber/Boston Children’s Cancer and Blood Disorders Center. “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.”

Stem cell transplant infusions include donor T-cells, a type of white blood cell that recognizes and destroys foreign invaders in the recipient’s body including cancer cells. GvHD occurs when the donor T-cells also recognize the patient’s healthy cells as foreign and start attacking healthy tissues and organs.1 T-cell activation requires a signaling process called co-stimulation. ORENCIA, a therapy currently approved to treat various arthritic conditions, binds to and inhibits protein targets involved in co-stimulation, thus inhibiting T-cell activation.

The Breakthrough Therapy Designation is based on findings from an investigator-initiated study supported by Bristol-Myers Squibb. This Phase 2 trial assessed the impact of ORENCIA on the prevention of severe acute GvHD, when added to a standard GvHD prophylactic regimen administered to patients with hematologic malignancies receiving a stem cell transplant from an unrelated, HLA-matched or mismatched donor. A mismatch in HLA increases the risk of GvHD.

Breakthrough Therapy Designation is an FDA program intended to expedite the development and review of medicines for serious or life-threatening diseases with preliminary clinical evidence that the investigational therapy may offer substantial improvement on at least one clinically significant endpoint over available therapy.

“We are excited about the potential of ORENCIA to improve outcomes for patients receiving unrelated stem cell transplants. We believe the data could lead to an expansion of the donor pool for stem cell transplants in some patient populations where fully matched unrelated donor transplants have rarely been available,” said Brian Gavin, Ph.D., development lead, ORENCIA, Bristol-Myers Squibb. “We look forward to working with the FDA and making ORENCIA the first approved therapy for the prevention of acute GvHD.”