Jaypirca: what changed in the evidence · Jaypirca · Jan 2023 – Oct 2026
Where does the confirmatory trial for Jaypirca's first indication stand?
Open. The mantle cell lymphoma indication is still an accelerated approval in the October 2026 label, and the FDA lists its confirmatory requirement as ongoing, with a projected completion of December 31, 2026. Lilly's 2025 10-K drops the indication from its pipeline table.
EphemerisX Research · Published · 7 source documents · 2 min read
Short answer
Open, on the FDA's record. The first indication, approved on response rate in January 2023, still carries its accelerated-approval wording in the October 2026 label. The FDA's list of ongoing accelerated approvals, current as of October 5, 2026, shows requirement 4389-1, a randomized trial against other BTK inhibitors, with a projected completion of December 31, 2026. Lilly's 2025 10-K still lists the indication among its products but not in its pipeline.
What the evidence shows
The 2023 requirement: 4389-1 Complete a randomized clinical trial to obtain data on the clinical efficacy and safety of pirtobrutinib in patients with mantle cell lymphoma. The trial should compare pirtobrutinib monotherapy to an investigator’s choice of approved BTK inhibitors in patients with mantle cell lymphoma
FDA · Jan 27, 2023 · p. 3. The condition attached: If required postmarketing clinical trials fail to verify clinical benefit or are not conducted with due diligence, we may withdraw this approval
FDA · Jan 27, 2023 · p. 3.
The trial in January 2023: The confirmatory trial intended to verify clinical benefit is the BRUIN MCL-321 trial (NCT04662255), a Phase 3 randomized study of pirtobrutinib vs. investigator’s choice of BTK inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) in patients with previously treated, BTK inhibitor-naïve MCL
FDA · Jan 27, 2023 · p. 194; As of 07/15/2022, 26% of patients have been enrolled
FDA · Jan 27, 2023 · p. 194.
October 2026: the label still reads Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial
FDA · Oct 2, 2026 · p. 3, and the FDA's list of ongoing accelerated approvals gives the approval date and projected completion: 1/27/2023
FDA · Oct 5, 2026 … 12/31/2026
FDA · Oct 5, 2026.
Lilly: its 2022 10-K said FDA granted accelerated approval (4) in the U.S. in January 2023. Phase III trial is ongoing
10-K · Feb 22, 2023. Its 2025 10-K product list still includes relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor
10-K · Feb 12, 2026, while its pipeline table lists Jaypirca only for CLL. Lilly's 10-K for 2025 does not mention accelerated approval, a confirmatory trial or BRUIN. 10-K · searched The 2025 CLL conversion letter is limited to CLL: The FDA's December 2025 conversion letter does not mention mantle cell lymphoma or its confirmatory requirement, 4389-1. FDA · searched
Follow the thread
- What uncertainty did the FDA's reviewers record when they approved Jaypirca in 2023?Requirement 4389-1
- What evidence allowed the FDA to convert Jaypirca's CLL/SLL approval to traditional approval?The conversion letter is CLL only
- How did Lilly describe each FDA decision on Jaypirca?“Phase III trial is ongoing”
- What stayed the same across Jaypirca's approvals?Unchanged accelerated wording
The documents, by date
The passages quoted
FDA approval letter, January 27, 2023 · page 3
4389-1 Complete a randomized clinical trial to obtain data on the clinical efficacy and safety of pirtobrutinib in patients with mantle cell lymphoma. The trial should compare pirtobrutinib monotherapy to an investigator’s choice of approved BTK inhibitors in patients with mantle cell lymphoma. The primary endpoint should be progression-free survival as assessed by an independent review committee, with secondary endpoints that include overall survival and objective response rate.Open at the source →
FDA approval letter, January 27, 2023 · page 3
If required postmarketing clinical trials fail to verify clinical benefit or are not conducted with due diligence, we may withdraw this approval.Open at the source →
FDA Multi-discipline Review, January 27, 2023 · page 194
The confirmatory trial intended to verify clinical benefit is the BRUIN MCL-321 trial (NCT04662255), a Phase 3 randomized study of pirtobrutinib vs. investigator’s choice of BTK inhibitor (ibrutinib, acalabrutinib, or zanubrutinib) in patients with previously treated, BTK inhibitor-naïve MCL. As of 07/15/2022, 26% of patients have been enrolled. This trial is considered to be well underway.Open at the source →
Lilly Form 10-K, filed February 22, 2023
Pirtobrutinib (Jaypirca TM ) Mantle cell lymphoma Approved (4) FDA granted accelerated approval (4) in the U.S. in January 2023. Phase III trial is ongoing.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 →Jaypirca: what changed in the evidence Form 10-K, filed February 12, 2026
Lilly's 10-K for 2025 does not mention accelerated approval, a confirmatory trial or BRUIN.
Open the document →Lilly Form 10-K, filed February 12, 2026
Jaypirca For the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have previously been treated with a covalent BTK inhibitor; and for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor.Open at the source →
FDA-approved label, October 2, 2026 · page 3
JAYPIRCA® is indicated for the treatment of adult patients with relapsed or refractory mantle cell lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor. This indication is approved under accelerated approval based on response rate [see Clinical Studies (14.1)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.Open at the source →
FDA list of ongoing cancer accelerated approvals, October 5, 2026
Jaypirca (pirtobrutinib) Adult patients with relapsed or refractory mantle cel lymphoma (MCL) after at least two lines of systemic therapy, including a BTK inhibitor. 1/27/2023 4389-1: Complete a randomized clinical trial to obtain data on the clinical efficacy and safety of pirtobrutinib in patients with MCL. The trial should compare pirtobrutinib monotherapy to an investigator’s choice of approved BTK inhibitors in patients with MCL. The primary endpoint should be PFS as assessed by an independent review committee, with secondary endpoints that include OS and objective response rate. The trial should enroll a sufficiently representative study population to reflect the racial and ethnic diversity of the U.S. patient population with MCL and allow for interpretation of the results in these patient populations. 12/31/2026Open at the source →