US FDA grants breakthrough therapy designation to Novartis STAMP inhibitor asciminib to treat chronic myeloid leukemia

Novartis announced that asciminib, a novel investigational treatment specifically targeting the ABL myristoyl pocket (STAMP), has been granted Breakthrough Therapy designation (BTD) by the US FDA for the treatment of adult patients with Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with two or more tyrosine kinase inhibitors (TKIs). Asciminib was also granted BTD for the treatment of adult patients with Ph+ CML in CP harboring the T315I mutation.

Despite tremendous advances in CML treatment over the past few decades, some of these pre-treated patients struggle to meet treatment goals due to resistance and intolerance. With few remaining treatment options, patients in later lines of care may be at risk of progression.

These US FDA designations, which may allow for an expedited development and review of asciminib, were based on the pivotal, phase III ASCEMBL trial, where asciminib was compared to Bosulif (bosutinib) in patients with Ph+ CML in CP previously treated with two or more TKIs. A phase I trial that included patients with Ph+ CML, some of them harboring the T315I mutation.

Asciminib (ABL001) is an investigational treatment specifically targeting the ABL myristoyl pocket (STAMP). As a STAMP inhibitor, asciminib is being studied in patients with chronic myeloid leukemia (CML) who experience resistance or intolerance to two or more tyrosine-kinase inhibitors (TKIs), and in several clinical trials in hopes of helping patients across multiple treatment lines of CML.

ASCEMBL is the first head-to-head clinical trial in chronic myeloid leukemia using a second-generation tyrosine-kinase inhibitor (TKI) as a comparator. As a phase III, multicenter, open-label, randomized study, ASCEMBL was designed to evaluate superiority in major molecular response rate at 24 weeks of the oral investigational treatment asciminib (ABL001) versus bosutinib in patients with Philadelphia-chromosome positive CML in chronic phase previously treated with two or more TKIs. Patients with failure or intolerance to the most recently administered TKI therapy were included in the trial.