BMS Submits sBLA for Orencia (Abatacept) to Prevent Acute Graft-versus-Host Disease in Hematopoietic Stem Cell Transplantation

On August 23, 2021, Bristol-Myers Squibb Company (BMS) announced that the U.S. FDA has granted Priority Review designation to its supplemental Biologics License Application (sBLA) for the immunomodulator Orencia (abatacept) for the prevention of moderate-to-severe acute graft-versus-host disease (aGvHD) in patients aged 6 years and older undergoing unrelated donor hematopoietic stem cell transplantation (HSCT). The PDUFA target date for this application is December 23, 2021. The press release noted that, if approved, Orencia would become the first therapy for the prevention of aGvHD.

Hematopoietic stem cell transplantation (HSCT) is an effective treatment for aggressive leukemia and other hematologic malignancies, and is typically the only curative option. However, patients receiving stem cell transplants from unrelated and human leukocyte antigen (HLA)-mismatched donors are at a high risk of developing aGvHD. aGvHD occurs in 30%–70% of patients. Consequently, the benefits of HSCT, particularly in the setting of unrelated donor transplantation, are partially offset by high transplant-related mortality, primarily driven by severe aGvHD and infections.

GvHD occurs when donor T cells recognize the patient's healthy cells as foreign and initiate an attack. This activation of T cells can lead to severe immune-mediated tissue damage in the host, with the skin, liver, and gastrointestinal tract being the most common targets. To initiate this attack, T cells must be activated through a signaling process known as co-stimulation. Orencia, a fusion protein composed of CTLA-4 and an Fc region, has been approved for the treatment of various arthritic conditions. It binds to and inhibits protein targets involved in co-stimulation, thereby suppressing T cell activation.

This sBLA application is based on the results of the Phase 2 ABA2 clinical trial and a real-world data study. The ABA2 trial evaluated the efficacy of current standard prophylaxis plus Orencia in preventing severe acute graft-versus-host disease (aGvHD) in adult and pediatric patients with hematologic malignancies who underwent stem cell transplantation from unrelated, HLA-matched, or HLA-mismatched donors. The trial results demonstrated that, compared with the control group, the treatment significantly reduced the incidence of severe aGvHD and associated morbidity, significantly improved aGvHD-free survival, and did not increase disease relapse. The findings from the real-world data analysis were consistent with the results of the ABA2 trial.

References:

[1] U.S. Food and Drug Administration Accepts for Priority Review Bristol Myers Squibb’s Application for Orencia (abatacept) for the Prevention of Acute Graft Versus Host Disease (aGvHD). Retrieved August 23, 2021, from https://www.businesswire.com/news/home/20210823005092/en/U.S.-Food-and-Drug-Administration-Accepts-for-Priority-Review-Bristol-Myers-Squibb%E2%80%99s-Application-for-Orencia-abatacept-for-the-Prevention-of-Acute-Graft-Versus-Host-Disease-aGvHD

(Original text abridged)

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