On Dec. 3, 2025 the FDA gave full approval to pirtobrutinib for use in chronic lymphocytic leukemia (CLL) after treatment with a covalent BTK inhibitor. Prior to this, its accelerated approval in 2023 had required that it be reserved for use only after receiving two prior therapies including a BTK inhibitor and a BCL-2 inhibitor which never seems to be its best use.
Its full “traditional” approval is good news as it often makes sense to continue with the success of blocking the B-cell receptor (BCR) through the BTK pathway, rather than switching to a therapy with a different mechanism of action. Pirtobrutinib binds to and inhibits BTK in a different way than the other three approved BTK inhibitors, and it often continues to work when those three are no longer active. This short animation explains the different binding mechanisms. Moreover, now that it is fully approved, it can be used a comparator in clinical trials for other drugs in the relapsed or refractory setting.
Click to read the full FDA press release.
