Innovent Biologics (01801) has announced that its marketed non-covalent (reversible) Bruton's tyrosine kinase (BTK) inhibitor Jaypirca (pirtobrutinib) has officially received approval from China's National Medical Products Administration (NMPA) for a new indication, as a monotherapy for the all-line treatment of adult patients with chronic lymphocytic leukemia (CLL) or 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 regardless of whether they have previously received a covalent BTK inhibitor, and it has demonstrated positive efficacy and safety results in these clinical trials.

The approval of this new indication is mainly based on results from 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-naive CLL/SLL patients. Results showed that pirtobrutinib achieved a significant progression-free survival (PFS) benefit compared with bendamustine plus rituximab (BR), with a hazard ratio (HR) of 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-naive patients. The study met its primary endpoint in both the intent-to-treat (ITT) population and the previously treated population. Pirtobrutinib demonstrated a higher objective response rate (ORR) as assessed by the independent review committee (IRC) compared with ibrutinib, with a nominal p-value of less than 0.05 for superiority. Although PFS data are not yet mature, a trend toward PFS benefit was observed. Together, the two studies support the clinical value of pirtobrutinib across all lines of treatment for 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 the chemoimmunotherapy regimen BR (bendamustine combined with rituximab) in previously untreated CLL/SLL patients without 17p deletion. The study enrolled 282 patients, who were randomly assigned 1:1 to receive pirtobrutinib (200 mg, once daily orally) or the BR regimen. BR is a chemoimmunotherapy regimen currently used for CLL treatment. The primary endpoint was PFS as assessed by blinded IRC. Secondary endpoints included ORR, duration of response (DoR), PFS, OS, time to next treatment (TTNT), safety and tolerability as assessed by investigators and the 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 those who were previously untreated (treatment-naive) and those who had received prior treatment but no BTK inhibitor. The study enrolled 662 patients, who were randomly assigned 1:1 to receive pirtobrutinib (200 mg, once daily orally) or ibrutinib (420 mg, once daily orally). The primary endpoint was ORR as assessed by blinded IRC. Secondary endpoints included PFS, DoR, event-free survival (EFS), TTNT, OS, safety and tolerability as assessed by investigators and the IRC, and PRO.

Jaypirca (pirtobrutinib, formerly known as LOXO-305) is a highly selective, non-covalent (reversible) BTK inhibitor. In preclinical studies, its selectivity for BTK was more than 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.