Pitobrutinib/Pitobrutinib (Zepali) indication scope and introduction to the main diseases treated

Pirtobrutinib is a new type of selective non-covalent Bruton's tyrosine kinase (BTK) inhibitor with a unique mechanism of action in the treatment of B cell malignancies. BTK is the core molecule of the B cell receptor signaling pathway. Its abnormal activation will promote B cell proliferation, inhibit apoptosis, and enhance the support of the tumor microenvironment to tumor cells, leading to the development of leukemia and lymphoma. Pitobrutinib binds to BTK in a non-covalent manner, effectively inhibiting its activity, thereby blocking abnormal signaling pathways, reducing pathological B cell proliferation, and has shown efficacy in some patients who have previously received covalent BTK inhibitors but are resistant.

In terms of indications, pitubrutinib is mainly used for the treatment of relapsed or refractory B cell malignancies, including chronic lymphocytic leukemia (CLL), small lymphocytes Lymphoma (SLL), mantle cell lymphoma (MCL), Waldenstrom's macroglobulinemia (WM), etc. For these patient groups, traditional chemotherapy or early targeted drugs often have limited effectiveness, especially when the disease progresses rapidly after multiple lines of treatment. Clinical trials have shown that pitubrutinib can achieve partial or complete remission in a variety of relapsed or refractory B cell tumors, significantly extend progression-free survival, and is generally well tolerated. The main side effects are mostly mild to moderate hematological abnormalities or gastrointestinal reactions.

Pitubrutinib has also shown significant efficacy in high-risk patients. For patients with CLL carrying 17p deletion or TP53 mutation, such patients usually have poor response to chemotherapy and conventional BTK inhibitors and have a high risk of disease progression. The mechanism of non-covalent BTK inhibitors enables them to overcome treatment failures caused by resistance to covalent BTK inhibitors, providing new treatment opportunities for high-risk patients. Studies have shown that most of these patients can achieve long-term disease control after receiving pitubrutinib treatment, and some patients even achieve complete remission, and the treatment is well tolerated.

In addition to monotherapy, pitubrutinib also shows potential in combination regimens. It works withBCL-2Inhibitors, anti-CD20 monoclonal antibodies or other targeted drugs are used in combination to enhance the anti-tumor effect and may also reduce the risk of drug resistance. Combination treatment strategies can not only increase the apoptosis rate of tumor cells through synergy, but also improve the efficacy of relapsed or refractory patients, providing more flexible treatment options for clinical practice. With the accumulation of more clinical data, pitubrutinib is expected to become an important targeted therapy drug in the field of B cell tumors, providing safe and effective treatment options for relapsed, refractory and high-risk patients.

The advantages of pitubrutinib also include convenient oral administration and good pharmacokinetic properties. It has good oral absorption and stable blood concentration. It can be used once a day or according to the doctor's plan, reducing the frequency of medical visits and the burden of treatment on patients. At the same time, the non-covalent binding properties also give the drug the ability to inhibit multiple drug-resistant mutations, making it more flexible in clinical applications. Overall, Pitobrutinib covers a wide range of B cell tumor types and is especially suitable for relapsed, refractory and high-risk patients. Its unique mechanism of action and clinical advantages are gradually being confirmed by practice and research, providing a new and important option for the treatment of hematological tumors.

Reference materials:https://go.drugbank.com/drugs/DB17472