Idelalisib

Jaypirca can now be used to treat patients with chronic lymphocytic leukemia or small lymphocytic lymphoma directly after treatment with another BTK inhibitor. With both a label expansion and a conversion to a full approval, Eli Lilly has earned the FDA’s go-ahead to act on the initial promise it saw with its BTK inhibitor Jaypirca (pirtobrutinib).Just about two years ago to the day, Lilly's non-covalent BTK inhibitor Jaypirca scored accelerated FDA approval to be used as a treatment for patients with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) who have tried at least two prior lines of therapy, specifically including a BTK inhibitor and a BCL-2 inhibitor.Unlike other BTK inhibitors such as AbbVie and Johnson & Johnson’s Imbruvica, AstraZeneca’s Calquence and BeOne Medicines’ Brukinsa, Jaypirca is able to help patients who have failed prior treatment with a covalent BTK inhibitor due to its non-covalent, or reversible, binding mechanism, according to Lilly.With the FDA’s new green light, Jaypirca can now treat patients with relapsed or refractory CLL/SLL earlier in their treatment course, directly following the use of a covalent BTK inhibitor, Lilly announced in a Dec. 3 press release. The later-line accelerated approval has also been converted into a traditional nod. It is in this earlier setting that the company has “always believed” Jaypirca “has its most unique potential impact for patients,” Lilly’s oncology head Jacob Van Naarden explained in the release. "With robust efficacy and safety evidence from the only study of its kind in the post-covalent BTK inhibitor treatment setting, we're proud to now offer this therapy to more patients with CLL or SLL at an earlier stage of their treatment plan."To confirm its benefits and support a traditional approval, Lilly studied Jaypirca against Gilead Sciences’ PI3K inhibitor Zydelig plus Roche’s Rituxan—or the chemotherapy bendamustine and Rixtuan—in patients with CLL or SLL who were pretreated with a BTK drug. In the 238-patient study called Bruin CLL-321, Jaypirca cut the risk of disease progression or death by 46% compared to either rival regimen, Lilly announced a year ago. Additionally, patients in the Jaypirca arm lived a median of 14 months without their disease worsening, whereas those in the control arm experienced a median 8.7 months of progression-free survival."When covalent BTK inhibitors are no longer an option due to disease progression or intolerance, pirtobrutinib enables physicians to extend the benefits of targeting the BTK pathway, offering continuity in the CLL or SLL treatment experience,” principal trial investigator Jeff Sharman, M.D., of the Willamette Valley Cancer Institute and Research Center, added in the release.Bruin CLL-321 is one of multiple studies Lilly is running to support Jaypirca’s broader use across CLL and SLL, which are two slow-growing forms of non-Hodgkin lymphoma. In September, Lilly demonstrated the drug’s ability to prompt improvements in progression-free survival over bendamustine and Rituxan in certain treatment-naïve patients, hailing “one of the most compelling effect sizes ever observed for a single agent BTK inhibitor in a front-line CLL study,” the company said at the time.That readout came after Jaypirca matched up to Imbruvica’s overall survival performance as a front-line treatment in a head-to-head study in July. Jaypirca came to Lilly from the Indianapolis pharma's $8 billion buyout of Loxo Oncology in 2019. The drug is still the only marketed non-covalent BTK inhibitor after its market debut in 2023. Last year, Jaypirca generated sales of $337 million.

On December 3, 2025, the Food and Drug Administration granted traditional approval to pirtobrutinib (Jaypirca, Eli Lilly and Company) for adults with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have previously been treated with a covalent BTK inhibitor. In 2023, FDA granted accelerated approval to pirtobrutinib for adults with CLL/SLL who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.Full prescribing information for Jaypirca will be posted here.Efficacy and SafetyEfficacy was evaluated in BRUIN-CLL-321 (NCT 04666038), a randomized, open-label, active-controlled trial. The trial randomized 238 patients who were previously treated for CLL/SLL, including a covalent BTK inhibitor. Patients previously treated with a non-covalent BTK inhibitor were not permitted. Patients were randomized (1:1) to receive either pirtobrutinib or investigator’s choice of idelalisib plus a rituximab product (IR) or bendamustine plus a rituximab product (BR). Crossover to JAYPIRCA monotherapy was permitted for patients in the investigator’s choice arm after confirmed disease progression.The primary efficacy outcome measure was progression-free survival (PFS), as assessed by an independent review committee using 2018 iwCLL criteria. Median PFS was 11.2 months (95% CI: 9.5, 11.4) in the pirtobrutinib arm and 8.7 months (95% CI: 7.2, 10.2) in the investigator’s choice of IR/BR arm (Hazard ratio 0.58 [95% CI: 0.38, 0.89]; p-value 0.0105). Of the 119 patients in the investigator’s choice arm, 50 crossed over to receive JAYPIRCA therapy. At an updated analysis with a median follow-up time of 19.8 months, the HR for overall survival (OS) was 1.09 (95% CI: 0.68, 1.75).The prescribing information includes warnings and precautions for infections, hemorrhage, cytopenias, cardiac arrythmias, secondary primary malignancies, hepatotoxicity, and embryo-fetal toxicity.Recommended DosageThe recommended pirtobrutinib dose is 200 mg orally once daily until disease progression or unacceptable toxicity.Expedited ProgramsThis review used the Assessment Aid, a voluntary submission from the applicant to facilitate the FDA’s assessment.Pirtobrutinib received orphan drug designation. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact OCE’s Project Facilitate at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov.Follow the Oncology Center of Excellence on X (formerly Twitter) @FDAOncology.