US Food and Drug Administration approvals for Bruton tyrosine kinase inhibitors in patients with chronic lymphocytic leukemia: Potential inefficiencies in trial design and evidence generation.

Abstract

The US Food and Drug Administration granted acalabrutinib approval as the second Bruton tyrosine kinase (BTK) inhibitor to treat patients with chronic lymphocytic leukemia and small lymphocytic lymphoma as monotherapy or in combination with obinutuzumab. This approval was based on 2 phase 3 trials: ELEVATE-TN and ASCEND. There are several concerns with the design of these trials, including suboptimal treatment of patients in the control arm, expansion of the trial population, and lack of data regarding efficacy or tolerability compared with ibrutinib, a first-in-class drug. The Food and Drug Administration approval of acalabrutinib for patients with chronic lymphocytic leukemia and small lymphocytic lymphoma represents concerning drug approval patterns in the United States and a weakness in evidence generation.