China's NMPA Expands Jaypirca (pirtobrutinib) to All Lines of CLL/SLL Therapy
核心洞察
China's NMPA approved Jaypirca (pirtobrutinib) as monotherapy for adults with CLL/SLL across all lines of therapy, regardless of prior covalent BTK inhibitor treatment.
The expanded label covers both treatment-naive and previously treated patients in China, where Eli Lilly developed the drug and Innovent Biologics (搜索) commercializes it.
In the Phase 3 BRUIN CLL-313 trial, pirtobrutinib reduced the risk of disease progression or death by 80.1% versus bendamustine plus rituximab (HR=0.199).
China's National Medical Products Administration (搜索) (NMPA) has approved Jaypirca (pirtobrutinib, 100 mg and 50 mg tablets) as a monotherapy for adults with chronic lymphocytic leukemia (搜索)/small lymphocytic lymphoma (搜索) (CLL/SLL), expanding the indication to cover all lines of therapy and patients regardless of prior treatment with a covalent BTK inhibitor. Innovent Biologics (搜索) announced the approval, which broadens use of the non-covalent Bruton tyrosine kinase (搜索) (BTK) inhibitor to both treatment-naive and previously treated patients in China.
Pirtobrutinib is a highly selective kinase inhibitor that uses a non-covalent binding mechanism to target the BTK pathway. Preclinical data describe it as 300 times more selective for BTK versus 98% of other kinases tested, and it is the first and only approved medicine that binds both wild-type and C481-mutated BTK. BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas, including mantle cell lymphoma and CLL. In China, the drug was developed by Eli Lilly and Company and is commercialized in mainland China by Innovent Biologics (搜索).
Phase 3 BRUIN Data Underpin the Label Expansion
The approval is supported by results from two global Phase 3 trials, BRUIN CLL-313 and BRUIN CLL-314.
BRUIN CLL-313 is described as the first prospective, randomized Phase 3 study to examine the efficacy and safety of a non-covalent BTK inhibitor in patients with treatment-naive CLL/SLL. The trial enrolled 282 patients without 17p deletions who had not been previously treated, randomizing them 1:1 to pirtobrutinib 200 mg orally once daily or bendamustine plus rituximab (BR) at labeled doses. The primary endpoint was progression-free survival (PFS) assessed by a blinded independent review committee (IRC). Pirtobrutinib demonstrated a statistically significant IRC-assessed PFS benefit versus BR, with a hazard ratio of 0.199, representing an 80.1% reduction in the risk of disease progression or death. Secondary endpoints included investigator- and IRC-assessed overall response rate (ORR), duration of response (DoR), PFS, overall survival (OS), time to next treatment (TTNT), safety and tolerability, and patient-reported outcomes.
BRUIN CLL-314 is the first head-to-head Phase 3 CLL/SLL trial to compare covalent and non-covalent BTK inhibitors in a BTK inhibitor-naive population, which included relapsed or refractory and treatment-naive patients. The study randomized 662 patients 1:1 to pirtobrutinib 200 mg orally once daily or ibrutinib 420 mg orally once daily. It met its primary endpoint of noninferiority for ORR as assessed by blinded IRC in both the intent-to-treat population and previously treated patients. Pirtobrutinib achieved a numerically higher ORR compared with ibrutinib. PFS data remain immature, although a trend toward PFS benefit was observed. Secondary endpoints included investigator- and IRC-assessed PFS, DoR, event-free survival, TTNT, OS, safety and tolerability, and patient-reported outcomes.
Investigators Point to Tolerability and Sequencing Needs
Prof. Jianyong Li, principal investigator of the BRUIN CLL-313 study in China, said BTK inhibitors have significantly transformed the treatment landscape for patients with CLL/SLL in recent years, but that a growing need remains for options combining durable efficacy with a favorable tolerability profile. He noted that pirtobrutinib has demonstrated meaningful clinical benefit in both treatment-naive and previously treated patients, and said the approval has the potential to provide a new option for Chinese patients across all lines of therapy.
Prof. Luqiu Qiu, principal investigator of the BRUIN CLL-314 study in China, said the treatment landscape for CLL or SLL is rapidly evolving with the emergence of non-covalent BTK inhibitors. He described pirtobrutinib's head-to-head evidence against a covalent BTK inhibitor in a BTK inhibitor-naive population as potentially offering an important treatment option for both treatment-naive and relapsed or refractory patients, regardless of prior covalent BTK inhibitor treatment.
Dr. Hui Zhou, chief R&D officer for the oncology pipeline at Innovent, called the approval another milestone in the collaboration between Innovent and Lilly and said the company will leverage its oncology commercial capabilities to accelerate patient access. Dr. Li Wang, Lilly corporate senior vice president and head of the Lilly China Drug Development and Medical Affairs Center, said the expanded indication reflects evidence generated from the BRUIN clinical program and expands the drug's potential to reach a broader CLL/SLL population, from relapsed or refractory disease to the frontline setting.
Disease Burden in China
CLL/SLL is a slow-growing form of non-Hodgkin lymphoma that develops from white blood cells known as lymphocytes, and it is one of the most common types of leukemia in adults. Roughly 100,000 new cases occur globally each year, and the overall incidence of CLL/SLL in China is estimated at approximately 0.39 per 100,000 population. In CLL/SLL, cancer cells are present in the blood.