FDA Grants Breakthrough Therapy Designation for GVHD Prevention Drug

The US Food and Drug Administration (FDA) has granted breakthrough therapy designation to abatacept (Orencia) to prevent moderate or severe acute graft-versus-host disease (GvHD) in patients who underwent a hematopoietic stem cell transplant and are not related to their donors, according to Bristol-Myers Squibb, the manufacturer of the drug.

Per the FDA, breakthrough therapy designation expedites the development and review of drugs when “preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapy on a clinically significant endpoint(s).”

An investigator-indicated, phase II study supported by Bristol-Myers Squibb led to the breakthrough therapy designation. The trial evaluated how well abatacept — which is currently used to treat arthritic conditions – prevented severe acute GvHD when the drug was combined with a standard GvHD prophylactic regimen in patients with hematologic malignancies receiving a stem cell transplant from an unrelated, HLA-matched or mismatched donor. Patients with an HLA mismatched donor tend to have a higher risk of acute GvHD – a potentially life-threatening complication that currently has no approved therapies.

“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, in a statement.

“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,” she added.

Stem cell transplants work by taking healthy donor T-cells and putting them in the patient’s body so that the T-cells can recognize and attack the cancer. To activate these cells, a process called co-stimulation must occur. However, GvHD can occur when these T-cells also see the patient’s healthy cells as foreign, and begin to attack.

Abatacept works by binding and inhibiting protein targets that are involved in co-stimulation. In doing so, it prevents T-cell activation.

“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.”