INNOVENT BIO (01801): Jaypirca (pirtobrutinib) approved in China for a new indication covering all lines of treatment for chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL)

INNOVENT BIO (01801) announced that Jaypirca (pirtobrutinib), a marketed non-covalent (reversible) Bruton's tyrosine kinase (BTK) inhibitor, has officially received approval from China's National Medical Products Administration (NMPA) for a new indication as monotherapy for all lines of treatment in adult patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Pirtobrutinib is a highly selective, non-covalent (reversible) BTK inhibitor. As a BTK inhibitor, its non-covalent binding mechanism enables clinical studies in CLL/SLL patients who have previously received or not received covalent BTK inhibitor treatment, and has demonstrated positive efficacy and safety results in relevant clinical studies. The approval of this new indication is primarily based on the results of two global Phase III clinical studies, BRUIN CLL-313 and BRUIN CLL-314. BRUIN CLL-313 is the world's first Phase III study specifically evaluating a non-covalent BTK inhibitor in treatment-nave CLL/SLL patients. Results showed that pirtobrutinib demonstrated a significant progression-free survival (PFS) benefit compared with bendamustine + rituximab (BR) (HR=0.199), reducing the risk of disease progression or death by 80.1%. BRUIN CLL-314 is the world's first Phase III study in the CLL/SLL field comparing a non-covalent BTK inhibitor with a covalent BTK inhibitor, and also the first study to directly compare two BTK inhibitors head-to-head in treatment-nave patients. The study met its primary endpoint in both the intent-to-treat (ITT) population and the previously treated population. Pirtobrutinib achieved higher objective response rates (ORR) as assessed by the Independent Review Committee (IRC) compared with ibrutinib, with a nominal p-value for superiority of <0.05. Although PFS data are not yet mature, there is a trend toward PFS benefit. Together, the two studies support the clinical value of pirtobrutinib across all lines of treatment in CLL/SLL patients. BRUIN CLL-313 is a global, randomized, open-label Phase III clinical study designed to evaluate the efficacy and safety of pirtobrutinib versus chemoimmunotherapy BR (bendamustine combined with rituximab) in previously untreated CLL/SLL patients without 17p deletion. The study enrolled a total of 282 patients, who were randomized 1:1 to receive pirtobrutinib (200 mg, once daily oral) or BR regimen. BR is a chemoimmunotherapy regimen currently used for CLL treatment. The primary endpoint is PFS assessed by blinded IRC. Secondary endpoints include ORR, duration of response (DoR), PFS, OS, time to next treatment (TTNT), safety and tolerability as assessed by investigators and IRC, and patient-reported outcomes (PRO). BRUIN CLL-314 is a Phase III, randomized, open-label clinical study designed to evaluate the efficacy and safety of Jaypirca (pirtobrutinib) versus Imbruvica (ibrutinib) in CLL/SLL patients. Enrolled patients included previously untreated (treatment-nave) patients and patients who had received prior treatment but no prior BTK inhibitor therapy. The study enrolled a total of 662 patients, who were randomized 1:1 to receive pirtobrutinib (200 mg, once daily oral) or ibrutinib (420 mg, once daily oral). The primary endpoint is ORR assessed by blinded IRC. Secondary endpoints include PFS, duration of response (DoR), event-free survival (EFS), time to next treatment (TTNT), overall survival (OS), safety and tolerability as assessed by investigators and IRC, and patient-reported outcomes (PRO). Jaypirca (pirtobrutinib, formerly known as LOXO-305) is a highly selective, non-covalent (reversible) BTK (Bruton's tyrosine kinase) inhibitor. In preclinical studies, its selectivity for BTK was 300 times higher than that for 98% of other kinases tested. BTK is a validated molecular target widely present in various B-cell leukemias and lymphomas, including mantle cell lymphoma (MCL) and CLL. In China, pirtobrutinib is developed by Eli Lilly, and the Company is responsible for its commercialization in mainland China. CLL/SLL is an indolent non-Hodgkin lymphoma originating from lymphocytes and is one of the most common types of leukemia in adults. There are approximately 100,000 new cases of CLL/SLL worldwide each year. In China, the overall incidence of CLL/SLL is approximately 0.39 per 100,000. In CLL/SLL patients, tumor cells are mainly present in the peripheral blood.