Jaypirca: what changed in the evidence · Jaypirca · Dec 2025
What evidence allowed the FDA to convert Jaypirca's CLL/SLL approval to traditional approval?
BRUIN CLL-321: 238 patients randomized against idelalisib or bendamustine with rituximab. Median progression-free survival was 11.2 months against 8.7, a hazard ratio of 0.58. The FDA wrote that the confirmatory requirement was fulfilled.
EphemerisX Research · Published · 5 source documents · 1 min read
Short answer
A randomized trial. BRUIN CLL-321 randomized 238 previously treated patients to pirtobrutinib or the investigator's choice of idelalisib or bendamustine with rituximab, the comparators the FDA had specified; median progression-free survival was 11.2 months against 8.7 (hazard ratio 0.58). The FDA's December 2025 letter states the Subpart H commitments and requirement 4557-1 fulfilled.
What the evidence shows
The trial, as the FDA describes it: Efficacy 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
FDA · Dec 3, 2025. The comparators were those the FDA had specified in 2023: an investigator’s choice arm of idelalisib plus rituximab or bendamustine plus rituximab
FDA · Dec 1, 2023 · p. 2.
The result: 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)
FDA · Dec 3, 2025.
The letter: Approval of this supplement fulfills your commitments made under 21 CFR 314.510
FDA · Dec 3, 2025 · p. 2. On 4557-1: We have reviewed your submission and conclude that the above requirement was fulfilled
FDA · Dec 3, 2025 · p. 3. It adds: We remind you that there is postmarketing requirement listed in the December 1, 2023, approval letter that is still open
FDA · Dec 3, 2025 · p. 3 (the dose trial, 4557-2). The FDA's December 2025 conversion letter does not mention mantle cell lymphoma or its confirmatory requirement, 4389-1. FDA · searched
The FDA's list of verified accelerated approvals records the dates: 12/1/2023 12/2/2025
FDA · Sep 17, 2026; the letter is signed and the announcement dated December 3. Lilly first reported the trial in February 2025: Positive Phase 3 results from the BRUIN CLL-321 trial
8-K · Feb 6, 2025. The FDA has posted a review only for the January 2023 approval; for the later decisions the record is the letters, the labels and the FDA's announcements.
Whether it covered the same patients: Did the traditional approval cover the same patients as the accelerated approval?
Follow the thread
- What evidence supported Jaypirca's accelerated approval in CLL/SLL?Requirement 4557-1
- Did the traditional approval cover the same patients as the accelerated approval?BRUIN CLL-321's population
- Where does the confirmatory trial for Jaypirca's first indication stand?The conversion letter is CLL only
- How did Lilly describe each FDA decision on Jaypirca?BRUIN CLL-321
The documents, by date
The passages quoted
FDA approval letter, December 1, 2023 · page 2
4557-1 Complete a randomized trial in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Patients should be randomized to receive pirtobrutinib or an investigator’s choice arm of idelalisib plus rituximab or bendamustine plus rituximab. The primary endpoint should be progression-free survival, with secondary endpoints that include response rate and overall survival.Open at the source →
Lilly Form 8-K, filed February 6, 2025
Positive Phase 3 results from the BRUIN CLL-321 trial evaluating pirtobrutinib, a non-covalent (reversible) Bruton's tyrosine kinase (BTK) inhibitor in adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) previously treated with a covalent BTK inhibitor;Open at the source →
FDA approval letter, December 3, 2025
The FDA's December 2025 conversion letter does not mention mantle cell lymphoma or its confirmatory requirement, 4389-1.
Open the document →FDA announcement, December 3, 2025
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).Open at the source →
FDA announcement, December 3, 2025
Efficacy 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.Open at the source →
FDA approval letter, December 3, 2025 · page 2
SUBPART H FULFILLED We approved this NDA under the regulations at 21 CFR 314 Subpart H for accelerated approval of new drugs for serious or life-threatening illnesses. Approval of this supplement fulfills your commitments made under 21 CFR 314.510.Open at the source →
FDA approval letter, December 3, 2025 · page 3
We have reviewed your submission and conclude that the above requirement was fulfilled. We remind you that there is postmarketing requirement listed in the December 1, 2023, approval letter that is still open.Open at the source →
FDA list of verified cancer accelerated approvals, September 17, 2026
Jayprica (pirtobrutinib) Adult patients 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 12/1/2023 12/2/2025Open at the source →