FDA Grants Accelerated Approval to Pirtobrutinib for Chronic Lymphocytic Leukemia and Small Lymphocytic Lymphoma
On December 1, 2023, the U.S. Food and Drug Administration (FDA) granted accelerated approval (https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pirtobrutinib-chronic-lymphocytic-leukemia-and-small-lymphocytic) to pirtobrutinib (Jaypirca™) for adults with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor.
Efficacy was evaluated in BRUIN (NCT03740529], an open-label, international, single-arm, multicohort trial that included 108 patients with CLL or SLL previously treated with at least two prior lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor. The study patients received a median of 5 prior lines of therapy (range = 2–11), and 77% discontinued their last BTK inhibitor because of refractory or progressive disease. During the trial, patients received 200 mg pirtobrutinib orally once daily until they experienced disease progression or unacceptable toxicity.
The main efficacy outcome measures were overall response rate (ORR) and duration of response (DOR), as assessed by an independent review committee using 2018 iwCLL criteria. The ORR was 72% (95% CI = 63, 80) and median DOR was 12.2 months (95% CI = 9.3, 14.7). All responses were partial responses.
The most common adverse reactions reported in 20% or more of the patients in the clinical trial, excluding laboratory abnormalities, were fatigue, bruising, cough, musculoskeletal pain, diarrhea, pneumonia, abdominal pain, dyspnea, hemorrhage, edema, nausea, pyrexia, and headache. More than 10% of patients experienced grade 3 or 4 anemia or decreased neutrophil or platelet counts. Serious infections occurred in 32% of patients, including fatal infections in 10% of patients. The prescribing information includes warnings and precautions for infections, hemorrhage, cytopenias, cardiac arrhythmias, and secondary primary malignancies.
The recommended pirtobrutinib dose is 200 mg orally once daily until disease progression or unacceptable toxicity.
FDA’s review was facilitated with the applicant’s voluntary Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid) submission. The application was granted priority review and orphan drug designation, as described in the Guidance for Industry: Expedited Programs for Serious Conditions—Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-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 (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.
For assistance with single-patient requests for investigational oncology products, healthcare professionals may call the Office of Oncology Excellence’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).