FDA Grants Accelerated Approval to Pirtobrutinib for Patients With CLL/SLL After Use of BTK, BCL-2 Inhibitors

Pirtobrutinib (Jaypirca) has received accelerated approval for use to treat patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) when their disease progresses after they receive 2 of the newer types of therapies on the market today.

Eli Lilly announced the approval late Friday in a statement.

Patients who have received a Bruton tyrosine kinase (BTK) inhibitor, such as ibrutinib, and a BCL-2 inhibitor, such as venetoclax, which targets the BCL-2 protein, could receive pirtobrutinib under the approval. Unlike its predecessors, pirtobrutinib is a third-generation non-covalent, or reversible, BTK inhibitor.

BRUIN trial. Approval is based on results from a subset of 108 patients enrolled in the phase 1/2 BRUIN trial, which found that pirtobrutinib could extend benefits of BTK inhibition in patients with CLL/SLL who have been treated with at least 2 prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor. Patients in the study treated with pirtobrutinib achieved an overall response rate of 72%.

Most of the patients in the BRUIN trial who had received an earlier-generation BTK inhibitor had been treated with ibrutinib, according to results published in the New England Journal of Medicine.

William G. Wierda, MD, PhD | Image credit: MD Anderson Cancer Center

"Once patients with CLL or SLL have progressed on covalent BTK inhibitor and BCL-2 inhibitor therapies, treatments are limited and outcomes can be poor, making the approval of [pirtobrutinib] a meaningful advance and much-needed new treatment option for these patients," William G. Wierda, MD, PhD, professor, medical director, and CLL section head for the Department of Leukemia at The University of Texas MD Anderson Cancer Center, said in the statement.

"[Pirtobrutinib] offers a new treatment option and different approach to targeting BTK, providing clinical benefit for a high proportion of patients with CLL or SLL in the BRUIN phase 1/2 trial whose disease progressed following treatment with a covalent BTK inhibitor and with a BCL-2 inhibitor."

Pirtobrutinib was previously approved to treat patients with relapsed or refractory mantle cell lymphoma after use of 2 prior therapies, including at least 1 BTK inhibitor.

Continued approval for this indication must be verified in a confirmatory trial.

Possible adverse effects for pirtobrutinib include infections, hemorrhage, cytopenias, cardiac arrhythmias, second primary malignancies, and embryo-fetal toxicity.