Characteristics of breakthrough therapy designation requests (BTDRs) submitted to the Office of Hematology and Oncology Products (OHOP), FDA.

Abstract

e18236 Background: Breakthrough therapy designation is an FDA program intended to expedite the development of drugs and biologics that provide preliminary clinical evidence of a substantial improvement over existing therapies. The factors needed to demonstrate this improvement in oncologic therapies have not been well-described. Methods: We reviewed the characteristics of BTDRs submitted to OHOP from program initiation to the present. Results: From November 2013 through July 2016, there were 134 BTDRs for 96 drugs submitted to OHOP, not including 14 BTDRs intended for benign hematologic or supportive care indications. The most common drug mechanisms of action (MoA) were tyrosine kinase inhibitor (TKI) (37; 28%), immunotherapy (24; 18%), and targeted antibodies (21; 16%). Of the 134 BTDRs, 56 (42%) were granted. BTDRs were granted most frequently for TKIs (22; 59%) and immunotherapy (14; 58%) and were rarely granted for cytotoxic (1; 10%) or endocrine (0) therapies. BTDRs based on randomized trials were more frequently granted than those based on single-arm trials (49% vs 39%), as were BTDRs based on OS versus ORR or PFS (57% vs 41%). In BTDRs based on single-arm trials, the median number of patients was higher in those granted versus denied or withdrawn (41 vs 26 patients). Among BTDRs granted based on ORR in solid tumors, the ORR ranged from 24% to 94%, reflecting variation in available therapies, MoA, toxicity, and durability of response. Conclusions: The likelihood of a successful BTDR increases with randomized trial design and larger sample size. Additional considerations include MoA, duration of ORR, and choice of endpoint. [Table: see text]