FDA Approves Jaypirca for Relapsed or Refractory CLL/SLL Previously Treated with Covalent BTK Inhibitors | iPharmaCenter
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The U.S. Food and Drug Administration has approved an expanded indication for Eli Lilly's Jaypirca (pirtobrutinib), making it the first and only non-covalent, reversible Bruton tyrosine kinase (BTK) inhibitor approved to treat adults with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have previously received covalent BTK inhibitor therapy. The approval also converts the company's December 2023 accelerated approval into a traditional full FDA approval.
What FDA approval of Jaypirca mean for CLL patients?
This expanded label allows Jaypirca to reach a substantially larger patient population—those earlier in their disease course who have already been treated with first‑generation covalent BTK inhibitors such as ibrutinib, acalabrutinib, or zanubrutinib. The approval aligns with recommendations from the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology and addresses a critical unmet need for patients who develop resistance or intolerance to standard covalent BTK‑targeting therapy.
BRUIN CLL-321 trial results
The FDA decision is based on data from the BRUIN CLL-321 Phase 3 trial, the only randomized, head‑to‑head study specifically designed to evaluate a BTK inhibitor in covalent BTK inhibitor–pretreated CLL/SLL patients. The study enrolled 238 patients who were randomly assigned to receive either Jaypirca (200 mg once daily) or investigator's choice of idelalisib plus rituximab or bendamustine plus rituximab. Key endpoints measured in the trial included progression‑free survival (PFS) assessed by an independent review committee, overall response rate (ORR), duration of response (DoR), overall survival (OS), time to next treatment (TTNT), and patient‑reported outcomes. The trial demonstrated that Jaypirca offered clinically meaningful benefit in this heavily pretreated population compared to standard salvage regimens.
Understanding Jaypirca's mechanism of action
Jaypirca is a highly selective BTK inhibitor with a novel non‑covalent (reversible) binding mechanism that distinguishes it from earlier‑generation covalent BTK inhibitors. Preclinical studies show Jaypirca is approximately 300 times more selective for BTK compared to 98 percent of other kinases tested, enabling potent and targeted BTK pathway inhibition with a favorable safety profile. The reversible binding approach allows Jaypirca to maintain BTK inhibition while potentially reducing the risk of acquired resistance mutations that can emerge with prolonged covalent BTK inhibitor exposure—a key advantage for patients who have progressed on or developed intolerance to first‑line covalent BTK inhibitors.
Dosing and administration of Jaypirca
Jaypirca is an oral medication administered as a 200 mg once‑daily dose (available as 100 mg or 50 mg tablets) with or without food. Patients continue treatment until disease progression or unacceptable toxicity.
About chronic lymphocytic leukemia and small lymphocytic lymphoma
CLL and SLL are related forms of indolent non‑Hodgkin lymphoma that arise from malignant B lymphocytes. CLL is one of the most common adult leukemias in the United States, accounting for approximately one‑quarter of all new leukemia diagnoses. The U.S. is projected to see roughly 23,690 new CLL cases this year. SLL is pathologically and immunophenotypically identical to CLL, with the principal difference being disease location: CLL involves circulating cancer cells in the blood, while SLL presents with cancer cells in the lymph nodes.
Clinical significance and market impact
The approval expands Jaypirca's addressable market and establishes it as a standard option for BTK inhibitor–experienced patients, a population that continues to grow as earlier BTK inhibitor generations face increasing rates of resistance and toxicity. By offering a reversible mechanism of action and demonstrating superiority over salvage chemotherapy combinations, Jaypirca addresses a substantial treatment gap in a disease with limited alternatives for heavily pretreated patients. Lilly's expanded label positions Jaypirca as a key asset in the company's oncology portfolio and strengthens its competitive standing in the CLL/SLL therapeutic space, where multiple BTK inhibitors and PI3K inhibitors currently compete for patients at various treatment lines.