FDA Approves Jaypirca for Relapsed/Refractory CLL or SLL

The U.S. Food and Drug Administration (FDA) has granted traditional approval to Jaypirca (pirobrutinib) for the treatment of adults with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who were previously treated with a covalent BTK inhibitor.

The approval was announced in a news release issued by the agency.

The FDA previously granted accelerated approval to Jaypirca for adults with CLL or SLL who had received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor, the agency noted in its announcement.

The effectiveness of Jaypirca was evaluated in the BRUIN-CLL-321 randomized, open-label, active-controlled trial of 238 patients who were previously treated for CLL or SLL, including with a covalent BTK inhibitor. Patients who were previously treated with a non-covalent BTK inhibitor were not permitted to participate in the trial, according to the FDA.

In the trial, patients were evenly randomized to receive either Jaypirca or an investigator’s choice of Zydelig (idelalisib) plus a rituximab product (IR) or bendamustine plus a rituximab product (BR), with crossover to Jaypirca monotherapy permitted for patients in the investigator’s choice arm after they experienced confirmed disease progression.

The median progression-free survival was 11.2 months in the Jaypirca arm and 8.7 months in the investigator’s choice arm. Additionally, 50 of the 119 patients in the investigator’s choice arm crossed over to receive Jaypirca treatment.

According to the agency, the prescribing information for Jaypirca includes warnings and precautions for infections, hemorrhage, cytopenias, cardiac arrythmias, secondary primary malignancies, hepatotoxicity and embryo-fetal toxicity. The recommended dosage of the drug is 200 milligrams orally once daily until disease progression or unacceptable toxicity.

How Does Jaypirca Work to Treat Cancer?

Jaypirca, which is a type of drug known as a tyrosine kinase inhibitor, works by blocking a protein called BTK, which may help keep cancer cells from growing, as the National Cancer Institute explains on its website.

“Once patients with CLL or SLL have progressed to covalent BTK inhibitors, such as [Imbruvica (ibrutinib)], [Calquence (acalabrutinib)] and [Brukinsa (Zanubrutinib)] or BCL-2 inhibitors such as [Venclexta (venetoclax)], treatment options are limited and outcomes are generally poor,” Dr. Juan Alderuccio, clinical site disease group leader in the lymphoma section at Sylvester Comprehensive Cancer Center, part of UHealth – University of Miami Health System, told CURE in a 2023 interview.

“The approval of a non-covalent BTK inhibitor such as [Jaypirca (pirtobrutinib)] represents a meaningful advance and a much-needed new treatment option for these patients,” Alderuccio said. “This approval offers a new treatment option and a different approach to targeting the BTK pathway, providing clinical benefit for many patients with CLL or SLL.”

Speaking at a 2023 CURE® Educated Patient® CLL Summit, Dr. Adam Kittai, an assistant professor at The James Cancer Center at The Ohio University Cancer Center, explained what distinguishes Jaypirca, a non-covalent BTK inhibitor.

“Covalent BTK inhibitors bind to the BTK protein [on cancer cells] in a very specific way,” Kittai explained. “[Jaypirca] is the next version of a BTK inhibitor. … It binds differently. This drug was designed to work specifically for patients who’ve already received those first-generation BTK inhibitors.”

Jaypirca, Kittai explained, is more selective in the way that it binds to the BTK molecule, and it is less likely to interact with other nearby molecules and cause side effects for patients.

References

1. “FDA grants traditional approval to pirtobrutinib for chronic lymphocytic leukemia and small lymphocytic lymphoma,” FDA; https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-traditional-approval-pirtobrutinib-chronic-lymphocytic-leukemia-and-small-lymphocytic?utm_medium=email&utm_source=govdelivery
2. “Jaypirca,” National Cancer Institute; https://www.cancer.gov/publications/dictionaries/cancer-terms/def/jaypirca
3. “Jaypirca, ‘Much-Needed’ Treatment for CLL and SLL, Approved by FDA,” CURE; https://www.curetoday.com/view/jaypirca-much-needed-treatment-for-cll-and-sll-approved-by-fda

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