What evidence did the FDA rely on when Jaypirca first received accelerated approval?

FDA announcement, January 27, 2023

Patients had a median of 3 prior lines of therapy, with 93% having 2 or more prior lines. The most common prior BTK inhibitors received were ibrutinib (67%), acalabrutinib (30%), and zanubrutinib (8%); 83% had discontinued their last BTK inhibitor due to refractory or progressive disease.

FDA announcement, January 27, 2023

The main efficacy measures were overall response rate (ORR) and duration of response (DOR), as assessed by an independent review committee using Lugano criteria. The ORR was 50% (95% CI: 41, 59) with a complete response rate of 13%. The estimated median DOR was 8.3 months (95% CI: 5.7, NE), and the estimated DOR rate at 6 months was 65.3% (95% CI: 49.8, 77.1).

FDA approval letter, January 27, 2023 · page 1

This NDA provides for the use of Jaypirca (pirtobrutinib) tablets for the treatment of adult patients with relapsed or refractory mantle cell lymphoma after at least two lines of systemic therapy, including a BTK inhibitor.

FDA approval letter, January 27, 2023 · page 2

Your application for Jaypirca was not referred to an FDA advisory committee because the application did not raise significant public health questions on the role of the drug in the diagnosis, cure, mitigation, treatment, or prevention of a disease.

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.

FDA Multi-discipline Review, January 27, 2023 · page 16

While the data related to durability of response are limited by the degree of early censoring, the ORR, coupled with demonstration of durability of response in those with adequate follow-up, supports the determination that pirtobrutinib has clinically meaningful activity in a highly refractory, BTK inhibitor-pretreated MCL patient population.

FDA Multi-discipline Review, January 27, 2023 · page 16

Because of the paucity of data in patients with one prior therapy, the recommended indication is restricted to patients with relapsed or refractory mantle cell lymphoma after at least two systemic therapies, including a BTK inhibitor.

FDA Multi-discipline Review, January 27, 2023 · page 192

The currently approved treatment options for relapsed/refractory MCL include BTK inhibitors (ibrutinib, acalabrutinib, zanubrutinib), brexucabtagene autoleucel, bortezomib, and lenalidomide, of which only bortezomib and lenalidomide have regular approval and are considered currently available therapies. Lenalidomide and bortezomib have demonstrated modest response rates in patients with R/R MCL (ranging from 26-31% in the pivotal studies) and data are not available with these agents for patients who are relapsed or refractory following a prior BTK inhibitor. Thus, based on the response rates and sufficient durability of response demonstrated by pirtobrutinib in a relapsed/refractory, BTK inhibitor pre-treated MCL patient population, the study demonstrates an advantage over available therapies.