The US FDA approved Jaypirca (pirtobrutinib) as monotherapy for adults with previously untreated chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) with no known 17p deletion, extending the non-covalent BTK inhibitor into the first-line setting.
The approval is based on the Phase III BRUIN CLL-313 trial, which randomized 282 previously untreated patients to pirtobrutinib or bendamustine plus rituximab. At a median follow-up of about 28 months, pirtobrutinib reduced the risk of progression or death by 80% versus bendamustine/rituximab (HR 0.20; p<0.0001), with median progression-free survival not reached compared with 33.5 months in the control arm.
Serious adverse reactions occurred in 28% of patients receiving pirtobrutinib, while 4.3% discontinued treatment because of adverse reactions. Pneumonia was the only serious adverse reaction reported in at least 3% of patients.
Pirtobrutinib is a reversible, non-covalent BTK inhibitor that binds independently of the C481 residue, allowing it to retain activity against C481-mutated BTK associated with resistance to covalent BTK inhibitors.