The American medicine authority FDA granted accelerated approval to pirtobrutinib for adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor. Pirtobrutinib is marketed by Eli Lilly under the brand name Jaypirca.
According to Eli Lilly, pirtobrutinib is the first non-covalent, or reversible, BTK inhibitor cleared in the US, as well as the first BTK inhibitor of any kind specifically okayed for MCL patients previously treated with a covalent BTK inhibitor.
The FDA based its approval on data from a subset of 120 MCL patients in the Phase I/II BRUIN study who received pirtobrutinib once daily until disease progression or unacceptable toxicity. Patients had been treated with a median of three prior lines of therapy, and all had received at least one prior line of therapy containing a covalent BTK inhibitor such as ibrutinib, acalabrutinib or zanubrutinib. The FDA noted that 83% of the participants had stopped their last BTK inhibitor due to refractory or progressive disease.
The overall response rate with pirtobrutinib was 50%, including 13% of patients who were in complete response. The median duration of response (DOR) in this analysis was 8.3 months, while the estimated DOR rate at six months was 65.3%. The drug’s prescribing information includes warnings and precautions for infections, haemorrhage, cytopenias, atrial fibrillation and flutter, and second primary malignancies.