The US FDA has granted breakthrough therapy designation for acalabrutinib (Calquence) as monotherapy for adult patients with chronic lymphocytic leukaemia (CLL).
Acalabrutinib is a highly selective Bruton tyrosine kinase (BTK) inhibitor. It binds covalently to BTK, thereby inhibiting its activity. In beta (B) cells, BTK signalling results in activation of pathways necessary for B-cell proliferation, trafficking, chemotaxis, and adhesion.
The FDA granted the designation based on positive results from the interim analyses of the ELEVATE-TN and ASCEND phase III clinical trials. Together the trials showed that acalabrutinib alone or in combination significantly increased the time patients lived without disease progression or death, with safety and tolerability that was consistent with its established profile.
ELEVATE-TN (ACE-CL-007) is a randomised, multicentre, open-label Phase III trial evaluating the safety and efficacy of acalabrutinib alone or in combination with obinutuzumab vs. chlorambucil in combination with obinutuzumab in previously-untreated patients with CLL.
ASCEND (ACE-CL-309) is a global open-label phase III trial evaluating acalabrutinib in previously-treated patients with CLL.
Acalabrutinib is currently approved for the treatment of adults with relapsed or refractory mantle cell lymphoma (MCL) in the US, Brazil, Qatar, the United Arab Emirates, Mexico, Argentina and recently Singapore and is being developed for the treatment of CLL and other blood cancers.
The drug was granted accelerated approval by the US FDA in October 2017 for the treatment of adult patients with MCL who have received at least one prior therapy, AstraZeneca said.