Jaypirca: what changed in the evidence · Jaypirca · Dec 2023

What evidence supported Jaypirca's accelerated approval in CLL/SLL?

Another response rate from the same study: 72% in 108 heavily pretreated patients, all partial responses, with a median duration of 12.2 months. The FDA required a randomized trial against idelalisib or bendamustine with rituximab, measuring progression-free survival.

EphemerisX Research · Published October 8, 2026 · 4 source documents · 2 min read

Short answer

A response rate from another single-arm cohort of BRUIN. In December 2023 the FDA granted accelerated approval for CLL/SLL after at least two lines of therapy, including a BTK inhibitor and a BCL-2 inhibitor, on an overall response rate of 72% in 108 patients (all partial responses) and a median duration of response of 12.2 months. It required a randomized confirmatory trial with progression-free survival as the endpoint.

What the evidence shows

The letter: Jaypirca 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 FDA · Dec 1, 2023 · p. 1, approved under accelerated approval pursuant to section 506(c) of the Federal Food, Drug, and Cosmetic Act (FDCA) and 21 CFR 314.510 FDA · Dec 1, 2023 · p. 1.

The patients and the result: Patients received a median of 5 prior lines of therapy (range: 2 to 11) FDA · Dec 1, 2023. 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 FDA · Dec 1, 2023. The FDA also reported that Serious infections occurred in 32% of patients including fatal infections in 10% of patients FDA · Dec 1, 2023.

The confirmatory requirement: 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 FDA · Dec 1, 2023 · p. 2. A second requirement, on dose: 4557-2 Conduct a randomized trial to characterize the safety and further assess the serious risks including infections, cytopenias, and hemorrhage, of at least two different dosages of pirtobrutinib not to exceed 200 mg once daily FDA · Dec 1, 2023 · p. 4.

The label: This indication is approved under accelerated approval based on response rate FDA · Dec 1, 2023 · p. 3. Lilly called it approval under the Accelerated Approval Program 8-K · Feb 6, 2024. 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. What converted it: What evidence allowed the FDA to convert Jaypirca's CLL/SLL approval to traditional approval?

Follow the thread

What evidence allowed the FDA to convert Jaypirca's CLL/SLL approval to traditional approval?Requirement 4557-1
Did the traditional approval cover the same patients as the accelerated approval?Based on response rate
What stayed the same across Jaypirca's approvals?A trial of lower doses
Did each approval build on the last, or rest on a new body of evidence?The comparators the FDA specified

The documents, by date

The passages quoted

FDA announcement, December 1, 2023

Serious infections occurred in 32% of patients including fatal infections in 10% of patients.

Open at the source →

FDA announcement, December 1, 2023

Patients received a median of 5 prior lines of therapy (range: 2 to 11). Seventy-seven percent of patients discontinued the last BTK inhibitor for refractory or progressive disease.

Open at the source →

FDA announcement, December 1, 2023

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.

Open at the source →

FDA approval letter, December 1, 2023 · page 1

It is approved under accelerated approval pursuant to section 506(c) of the Federal Food, Drug, and Cosmetic Act (FDCA) and 21 CFR 314.510

Open at the source →

FDA approval letter, December 1, 2023 · page 1

This “Prior Approval” sNDA provides for a new indication: Jaypirca 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.

Open at the source →

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 →

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 approval letter, December 1, 2023 · page 4

4557-2 Conduct a randomized trial to characterize the safety and further assess the serious risks including infections, cytopenias, and hemorrhage, of at least two different dosages of pirtobrutinib not to exceed 200 mg once daily in patients with CLL or SLL.

Open at the source →

Lilly Form 8-K, filed February 6, 2024

FDA approval of Jaypirca ® 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, under the Accelerated Approval Program;

Open at the source →