Jaypirca: what changed in the evidence · Jaypirca · 2023 – 2026
What changed in the evidence behind Jaypirca's FDA approvals?
The kind of evidence. The two 2023 approvals rested on response rates in single-arm cohorts of one study and were granted as accelerated approvals; the 2025 and 2026 approvals rested on randomized trials measuring progression-free survival against a comparator.
EphemerisX Research · Published · 9 source documents · 1 min read
Short answer
The kind of evidence changed. In 2023 the FDA granted two accelerated approvals “based on response rate” in single-arm cohorts of the BRUIN study, 120 patients with mantle cell lymphoma and 108 with CLL/SLL. In 2025 it converted the CLL/SLL approval to traditional approval on BRUIN CLL-321, a randomized trial with progression-free survival as its endpoint, and in 2026 it approved a new indication on a second randomized trial, BRUIN CLL-313. The mantle cell lymphoma indication still rests on its response rate.
What the evidence shows
2023, mantle cell lymphoma: This indication is approved under accelerated approval based on response rate
FDA · Jan 27, 2023 · p. 3. The study was an open-label, multicenter, single-arm trial of pirtobrutinib monotherapy that included 120 patients with MCL previously treated with a BTK inhibitor
FDA · Jan 27, 2023.
2023, CLL/SLL: the same basis, This indication is approved under accelerated approval based on response rate
FDA · Dec 1, 2023 · p. 3, in an open-label, international, single-arm, multicohort trial that included 108 patients with CLL or SLL
FDA · Dec 1, 2023.
2025: the FDA's letter describes a Confirmatory study for pirtotobrutinib in Chronic Lymphocitic Leukemia (CLL)/ Small Lymphocytic Lymphoma (SLL) to support the conversion from accelerated approval to traditional approval
FDA · Dec 3, 2025 · p. 1 (the misspellings are the FDA's). The trial: a randomized, open-label, active-controlled trial
FDA · Dec 3, 2025, with The primary efficacy outcome measure was progression-free survival (PFS)
FDA · Dec 3, 2025.
2026: a new indication on a second randomized trial, BRUIN CLL-313 (NCT05023980), a randomized, open-label, active-controlled trial in 282 patients with previously untreated CLL/SLL without deletion of chromosome 17p
FDA · Oct 2, 2026. The FDA's October 2, 2026 approval letter does not mention accelerated approval, a confirmatory trial or a postmarketing requirement. FDA · searched
What did not change: the mantle cell lymphoma indication, which the October 2026 label still describes as approved under accelerated approval based on response rate
FDA · Oct 2, 2026 · p. 3. The decisions side by side: How do Jaypirca's four FDA decisions compare, side by side?
Follow the thread
- What evidence did the FDA rely on when Jaypirca first received accelerated approval?Accelerated approval on response rate
- What evidence supported Jaypirca's accelerated approval in CLL/SLL?Accelerated approval on response rate
- What evidence allowed the FDA to convert Jaypirca's CLL/SLL approval to traditional approval?BRUIN CLL-321, randomized
- What evidence supported Jaypirca's approval in previously untreated CLL/SLL?No accelerated-approval terms in 2026
The documents, by date
The passages quoted
FDA announcement, January 27, 2023
Efficacy was evaluated in BRUIN (NCT03740529), an open-label, multicenter, single-arm trial of pirtobrutinib monotherapy that included 120 patients with MCL previously treated with a BTK inhibitor.Open at the source →
FDA-approved label, January 27, 2023 · 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 announcement, December 1, 2023
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.Open at the source →
FDA-approved label, December 1, 2023 · page 3
JAYPIRCA is indicated for the treatment of 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. This indication is approved under accelerated approval based on response rate [see Clinical Studies (14.2)]. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.Open at the source →
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 1
Confirmatory study for pirtotobrutinib in Chronic Lymphocitic Leukemia (CLL)/ Small Lymphocytic Lymphoma (SLL) to support the conversion from accelerated approval to traditional approval.Open at the source →
FDA approval letter, October 2, 2026
The FDA's October 2, 2026 approval letter does not mention accelerated approval, a confirmatory trial or a postmarketing requirement.
Open the document →FDA announcement, October 2, 2026
Efficacy was evaluated in BRUIN CLL-313 (NCT05023980), a randomized, open-label, active-controlled trial in 282 patients with previously untreated CLL/SLL without deletion of chromosome 17p. Patients were randomized 1:1 to receive pirtobrutinib (n=141) until disease progression or bendamustine plus a rituximab product (n=141) for six cycles.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 →