Lilly’s Jaypirca approved in China for relapsed CLL/SLL after prior BTKi therapy

Jaypirca (pirtobrutinib), a non-covalent Bruton’s tyrosine kinase (BTK) inhibitor developed by Eli Lilly and commercialized in mainland China by Innovent Biologics, has been approved by China’s National Medical Products Administration (NMPA) for adult patients with chronic lymphocytic leukemia or small lymphocytic lymphoma (CLL/SLL) who have received at least one prior line of systemic therapy including a covalent BTK inhibitor.

The decision marks the drug’s second approval in China, following an October 2024 authorization for relapsed or refractory mantle cell lymphoma. It also makes Jaypirca the first non-covalent BTK inhibitor approved for CLL/SLL in China, expanding treatment options for patients whose disease progresses after standard BTK inhibitor therapy.

Indication and dosing

The NMPA approval covers pirtobrutinib as a 200 mg once-daily oral monotherapy administered continuously until disease progression or unacceptable toxicity. Eligible patients must have previously received a covalent BTK inhibitor such as ibrutinib, acalabrutinib, or zanubrutinib.

The Chinese indication is broader than the current US FDA label. In the US, pirtobrutinib received accelerated approval in December 2023 for patients with relapsed or refractory CLL/SLL after at least two prior lines of therapy including both a BTK inhibitor and a BCL-2 inhibitor. China’s approval does not require prior BCL-2 inhibitor exposure.

Evidence from BRUIN CLL-321

The approval is based on results from BRUIN CLL-321, an international Phase III trial enrolling 238 patients with CLL/SLL previously treated with a covalent BTK inhibitor. Participants were randomized to receive either pirtobrutinib or investigator’s choice of idelalisib plus rituximab or bendamustine plus rituximab.

The primary endpoint, progression-free survival assessed by independent review, showed a clear advantage for pirtobrutinib. Median PFS reached 14.0 months compared with 8.7 months in the control arm, corresponding to a hazard ratio of 0.54.

Tolerability also favored pirtobrutinib. Treatment discontinuation due to adverse events occurred in 5.2% of patients receiving pirtobrutinib versus 21.1% in the comparator group. The data were presented at the 2024 American Society of Hematology Annual Meeting.

Addressing post-BTK resistance

Covalent BTK inhibitors such as ibrutinib, acalabrutinib, and zanubrutinib have become foundational therapies in CLL. However, resistance frequently develops through mutations at the BTK C481 binding site that prevent covalent inhibitor binding.

Pirtobrutinib binds reversibly to BTK and does not rely on the C481 residue, allowing it to retain activity against these resistant clones. While additional mutations may eventually emerge under treatment, the drug offers a new therapeutic option in a setting where alternatives have historically been limited.

CLL accounts for roughly 6–7% of non-Hodgkin lymphoma cases in China. As use of covalent BTK inhibitors expands in earlier lines of therapy, the number of patients requiring treatment after BTK inhibitor failure is expected to grow.

The availability of pirtobrutinib introduces a new sequencing strategy — covalent BTK inhibitor followed by non-covalent BTK inhibition — alongside existing options such as venetoclax-based regimens.