Institute of Pathology
Micrograph showing APL Image courtesy of the Armed Forces
The US Food and Drug Administration (FDA) has accepted for priority review a supplemental new drug application (sNDA) for arsenic trioxide (TRISENOX®) injection.
With this sNDA, Teva Pharmaceutical Industries Ltd. is seeking approval for arsenic trioxide to be used in combination with all-trans retinoic acid (ATRA) for induction of remission and consolidation in patients with newly diagnosed, low- or intermediate-risk acute promyelocytic leukemia (APL) characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.
Currently, arsenic trioxide is FDA-approved as monotherapy for induction of remission and consolidation in patients with APL who are refractory to, or have relapsed from, retinoid and anthracycline chemotherapy, and whose APL is characterized by the presence of the t(15;17) translocation or PML/RAR-alpha gene expression.
For more details, see the full prescribing information.
The FDA has accepted the arsenic trioxide sNDA for priority review and expects to make a decision on the application in the first quarter of 2018.
The FDA grants priority review to applications for products that may provide significant improvements in the treatment, diagnosis, or prevention of serious conditions.
The agency’s goal is to take action on a priority review application within 6 months of receiving it, rather than the standard 10 months.
Phase 3 study results
The sNDA for arsenic trioxide is supported by results from the APL0406 study. Updated results from this phase 3 study were published in the Journal of Clinical Oncology in February.
The study included 276 adults (ages 18 to 71) with newly diagnosed, low- or intermediate-risk APL. Patients were randomized to receive ATRA plus arsenic trioxide or ATRA plus chemotherapy.
A total of 263 patients were evaluable for response to induction. One hundred percent of patients in the arsenic trioxide arm (127/127) achieved a complete response (CR), as did 97% (132/136) of patients in the chemotherapy arm (P=0.12).
After a median follow-up of 40.6 months, the event-free survival was 97.3% in the arsenic trioxide arm and 80% in the chemotherapy arm (P<0.001). The cumulative incidence of relapse was 1.9% and 13.9%, respectively (P=0.0013).
At 50 months, the overall survival was 99.2% in the arsenic trioxide arm and 92.6% in the chemotherapy arm (P=0.0073).
After induction, there were 2 relapses and 1 death in CR in the arsenic trioxide arm.
In the chemotherapy arm, there were 2 instances of molecular resistance after third consolidation, 15 relapses, 5 deaths in CR, and 2 patients who developed a therapy-related myeloid neoplasm.
