FDA Approves Pirtobrutinib for Newly Diagnosed CLL After a Trial Showed an 80% Lower Risk of Progression
The FDA has approved pirtobrutinib (Jaypirca) for adults with previously untreated chronic lymphocytic leukemia, after a 282-patient trial found it cut the risk of progression or death by 80% compared with chemoimmunotherapy.
The U.S. Food and Drug Administration approved pirtobrutinib, sold as Jaypirca by Eli Lilly, on October 2 for adults with previously untreated chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have no known 17p deletion, according to the FDA. The approval moves the drug into the first-line setting for these patients.
What the BRUIN CLL-313 trial found
The approval rests on BRUIN CLL-313, a randomized phase 3 trial of 282 patients split evenly between pirtobrutinib and six cycles of bendamustine plus rituximab, an older chemoimmunotherapy regimen. After a median follow-up of 28 months, the hazard ratio for progression or death was 0.20, which means pirtobrutinib reduced that risk by 80%. Median progression-free survival had not been reached on pirtobrutinib, against 33.5 months with chemoimmunotherapy.
Lilly reports that 94% of patients on pirtobrutinib responded to treatment, compared with 81% on chemoimmunotherapy. Complete responses were less common with pirtobrutinib, at 13% versus 21%. Overall survival had not been reached in either group, with 3 deaths in the pirtobrutinib arm and 10 in the comparison arm, per the Lilly announcement.
A different kind of BTK inhibitor
Pirtobrutinib is the first approved non-covalent BTK inhibitor. Earlier drugs in the class, including ibrutinib, acalabrutinib and zanubrutinib, bind to their target covalently, while pirtobrutinib binds reversibly. The comparison in this trial was against chemoimmunotherapy, not against those other BTK inhibitors, so the results do not show how it stacks up against them.
Side effects and who may be eligible
The most common adverse reactions, each affecting at least one in five patients, were upper respiratory infections (27%), rash (22%) and COVID-19 (21%). Adverse reactions led to permanent discontinuation in 4.3% of patients, and atrial fibrillation or flutter affected 1.4%. The recommended dose is 200 mg by mouth once daily until the disease progresses or side effects become unacceptable. About 22,760 Americans are diagnosed with CLL each year, and 92% to 95% of them lack the 17p deletion, according to Lilly.
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