FDA Approves BMS’s CTLA-4 Fusion Protein Orencia as First Therapy to Prevent Fatal Complication in Stem Cell Transplantation

On December 15, 2021, the U.S. FDA announced the approval of the supplemental Biologics License Application (sBLA) for Orencia (abatacept) to be used in combination with certain immunosuppressants for the prevention of acute graft-versus-host disease (aGVHD) in pediatric patients 2 years of age or older or adult patients. This is a potentially fatal complication that can occur after receiving a hematopoietic stem cell transplant (HSCT) from an unrelated donor. The press release noted that Orencia is the first FDA-approved therapy for the prevention of aGVHD.

HSCT is an effective treatment for aggressive leukemia and other malignant hematologic tumors and is often the only curative option. However, patients receiving stem cell transplants from unrelated or human leukocyte antigen (HLA)-mismatched donors are at high risk of developing aGVHD. With 30%-70% of patients experiencing aGVHD, some of the benefits of hematopoietic stem cell transplantation, particularly in unrelated donor transplants, are offset by high transplant-related mortality primarily due to severe aGVHD and infections.

GVHD occurs when donor T cells recognize the patient's healthy cells as foreign and begin to 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 require activation through a signaling process known as co-stimulation. Orencia, a fusion protein consisting of CTLA-4 and Fc, has been approved for the treatment of various arthritis conditions. It binds to and inhibits protein targets involved in co-stimulation, thereby suppressing T cell activation.

This approval is based on the results of a Phase 2 clinical trial and a study utilizing real-world data. The Phase 2 clinical trial results demonstrated that, among 186 adult or pediatric patients (aged 6 years and above) with malignant hematological diseases who received stem cell transplants from unrelated donors with HLA-matched or mismatched donors, the combination of the current standard prophylactic regimen plus Orencia significantly reduced the incidence of severe aGVHD and related morbidity, markedly increased aGVHD-free survival rates (50% vs. 32%), without increasing the rate of disease recurrence. The findings from the real-world data analysis were consistent with those of the Phase 2 clinical trial. Specifically, six months post-transplant, the overall survival rate was 98% for patients treated with Orencia, compared to 75% for those receiving standard immunosuppressive therapy alone.

Note: The original text has been abridged.

References:

[1] FDA Approves First Drug to Prevent Graft Versus Host Disease. Retrieved December 15, 2021, from https://www.fda.gov/news-events/press-announcements/fda-approves-first-drug-prevent-graft-versus-host-disease

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