On October 30, Eli Lilly China announced that its non-covalent (reversible) BTK inhibitor Jepalit (pirapatinib 100 mg and 50 mg tablets) has been approved by the National Medical Products Administration (NMPA), as a monotherapy for relapsed or refractory mantle cell lymphoma (MCL) adult patients who have received at least two prior systemic treatments, including a Bruton's tyrosine kinase (BTK) inhibitor.

Pirapatinib is a highly selective kinase inhibitor that uses a novel binding mechanism, allowing it to re-establish BTK inhibition in MCL patients previously treated with covalent BTK inhibitors (including ibrutinib, acalabrutinib, zanubrutinib, or orelabrutinib), and sustain the benefits of targeting the BTK pathway.

With the widespread use of BTK inhibitor drugs, resistance in patients has emerged. Covalent BTK inhibitors like ibrutinib, zanubrutinib, acalabrutinib, and orelabrutinib function by binding to the C481 residue of BTK, blocking the ATP-binding pocket, inhibiting BTK enzyme activity, and exerting anti-tumor effects. However, C481 mutations can lead to resistance. In contrast, the non-covalent inhibitor pirapatinib does not rely on C481 and can selectively bind to BTK, overcoming resistance caused by C481 mutations.

Professor Zhu Jun from Peking University Cancer Hospital, the lead investigator of the JZNJ study, stated: "The approval of pirapatinib is significant for patients with relapsed or refractory MCL. These patients who have previously received covalent BTK inhibitor treatments have limited current treatment options, with data suggesting a poor prognosis with a median survival of only 4-10 months after discontinuation of covalent BTK inhibitor therapy. The approval of pirapatinib brings a new alternative for MCL patients in China who have received prior covalent BTK treatment."

Previously, in January 2023, pirapatinib received approval from the U.S. FDA, becoming the world's first approved non-covalent (reversible) BTK inhibitor. In October 2023, pirapatinib was included in the priority review and approval by the Center for Drug Evaluation (CDE) of the National Medical Products Administration.

Publicly available data shows that there are currently 6 BTK inhibitors approved globally, including ibrutinib, acalabrutinib, zanubrutinib, tirabrutinib, orelabrutinib, and pirapatinib.

According to Frost & Sullivan's estimates, with the increasing number of cancer patients and the expanding indications of this drug, the global market size of BTK inhibitors is expected to reach $20 billion in 2025 and $26.1 billion in 2030. Specifically for China, after ibrutinib was approved for market in 2017, the market size is projected to reach 13.1 billion yuan by 2025 and expand to 22.5 billion yuan by 2030.

Facing a market worth billions, BTK inhibitors have always been the focus of research and development for various companies. Overseas, Sanofi, Roche, Merck, domestically Jiangsu Hengrui Pharmaceuticals, hutchmed (china), China Aba / the cigna group, Yondelis, and Haibo Pharmaceuticals and other pharmaceutical companies have all laid out their strategies.