FDA grants priority review to Orencia for acute GVHD prevention
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The FDA granted priority review to abatacept for prevention of moderate to severe acute graft-versus-host disease among patients aged 6 years or older receiving unrelated donor hematopoietic stem cell transplantation.
Abatacept (Orencia, Bristol Myers Squibb) is an immunomodulator designed to disrupt the continuous cycle of T-cell activation. It is approved in the United States for treatment of certain patients with arthritis.
Approximately 30% to 70% of patients who undergo HSCT develop acute GVHD.
This activation of T cells can lead to severe immune-mediated tissue damage to the host, with the most common targets being the skin, liver and gastrointestinal tract. Damage to these organs due to acute GVHD increases risk for morbidity and mortality.
There are no FDA-approved treatments for prevention of acute GVHD.
“For patients who receive unrelated donor stem cell transplants — in particular for racial and ethnic minority patient populations — there is a heightened risk of developing [acute GVHD], a potentially life-threatening medical complication for which there are no approved preventive therapies,” Mary Beth Harler, MD, head of immunology and fibrosis development for Bristol Myers Squibb, said in a company-issued press release. “We look forward to working with the FDA to bring Orencia to this new patient population.”
The agency based the priority review of abatacept on results of the phase 2 ABA2 trial, designed to evaluate the agent for prevention of acute GVHD among adults and children.
The multicenter trial included two cohorts. A single-arm cohort included patients who received transplants from mismatched unrelated donors. Another cohort included randomly assigned patients who received transplants from matched unrelated donors.
All patients received a calcineurin inhibitor beginning on day –2 and continuing through at least day 100, as well as methotrexate on days 1, 3, 6 and 11.
Abatacept-treated patients received 10 mg/kg on days –1, 5, 14 and 28.
Results showed the addition of abatacept to standard prophylaxis resulted in significantly higher acute GVHD-free survival at 180 days after transplant compared with registry controls in the single-arm mismatched unrelated donor cohort, as well as numerically higher severe acute GVHD-free survival in the matched unrelated cohort.
“[Although] stem cell transplants are an effective treatment for aggressive leukemias and other hematological malignancies, patients who receive stem cell transplants from unrelated and human leukocyte antigens (HLA)-mismatched donors are at high risk for developing [acute GVHD],” lead investigator Leslie Kean, MD, PhD, director of the pediatric stem cell transplantation program at Boston Children's Hospital/Dana-Farber Cancer Institute, said in the release. “There is a tremendous need to expand the stem cell donor pool by lowering the risk of [acute GVHD among] both adults and children receiving unrelated donor stem cell transplants.”
The FDA is expected to make a decision on the application by Dec. 23.
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