The Food and Drug Administration (FDA) has granted an accelerated approval to the anti-CD19 immunotherapy Blincyto (blinatumomab) as a treatment for patients with Philadelphia chromosome-negative relapsed/refractory B-precursor acute lymphoblastic leukemia (ALL), based on findings from a phase 2 trial.
Blincyto, a novel antibody specific to CD19 and CD3, demonstrated a complete remission rate (CR) of 32 percent for a median duration of 6.7 months, according to the FDA. Additionally, the rate of CR or CR with partial hematological (CRh) was 42 percent.
A decision on the new drug application for Blincyto was not expected until May, placing the agency's actions well ahead of deadline. The rapid approval follows a priority review and a breakthrough therapy designation, and establishes Blincyto as the first approved agent to target CD19, a promising target under exploration for patients with B-cell malignancies.
“Immunotherapies, especially Blincyto with its unique mechanism of action, are particularly promising for patients with leukemia,” Richard Pazdur, MD, director of the Office of Hematology and Oncology Products in FDA's Center for Drug Evaluation and Research, said in a statement. “Recognizing the potential of this novel therapy, the FDA worked proactively with the sponsor under our breakthrough therapy designation program to facilitate the approval of this novel agent.”
In the study, intravenous Blincyto was administered for four weeks followed by a two-week resting period for up to five cycles to 189 patients with Ph-negative ALL. The median age of patients was 39, and 34.1 percent had undergone a hematopoietic stem cell transplantation (HSCT) prior to entering the trial. The primary endpoint of the study was CR or CRh, with secondary endpoints focused on CR, CRh, relapse-free survival and overall survival (OS).
Overall, 80 percent of patients who achieved a CR also responded by minimal residual disease (MRD) testing. Approximately 39 percent of patients who achieved a CR/CRh went on to receive a HSCT.
According to data at the annual meeting of the American Society of Clinical Oncology this past summer, the median relapse-free survival was 5.9 months with Blincyto and the median OS was 6.1 months. A total of 74 percent of patients were minimal residual disease responders.
The most common all-grade adverse events were fever, headache and nausea, among other side effects. In all, three patients died due to treatment-related adverse events, which included sepsis and candida infection.
Neurological side effects occurred in approximately 50 percent of patients, resulting in treatment discontinuation. Additionally, 11 percent experienced cytokine release syndrome. To address these side effects, the FDA approved Blincyto with a Boxed Warning and Risk Evaluation and Mitigation Strategy (REMS).
An open-label phase 3 study comparing Blincyto with chemotherapy is currently enrolling patients with relapsed or refractory B-precursor ALL (NCT02013167). The primary endpoint of this study is overall survival.