Takeda's Next-generation ALK Inhibitor Alunbrig Is Approved By Japan

- Feb 11, 2021-

Takeda Pharmaceuticals (Takeda) recently announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved the targeted anticancer drug Alunbrig (brigatinib, 30mg, 90mg, tablets) as a first-line and second-line treatment for the treatment of unresectable, Patients with advanced or recurrent anaplastic lymphoma kinase fusion gene positive (ALK+) non-small cell lung cancer (NSCLC).

This approval is mainly based on the results of the Brigatinib-2001 (J-ALTA) Japanese Phase 2 study and the AP26113-13-301 (ALTA-1L) Global Phase 3 study. The previous study was carried out in Japan and involved 72 patients with unresectable advanced or relapsed ALK+NSCLC who had progressed after receiving an ALK tyrosine kinase inhibitor (TKI) treatment; the latter study focused on previous Patients with unresectable advanced or recurrent ALK+NSCLC who have not received ALK-TKI treatment.

Makoto Nishio, the chief investigator of the J-ALTA clinical trial and a medical doctor of thoracic oncology at the Cancer Research Institute Hospital of the Japan Cancer Research Foundation, said: “Although the diagnosis, detection and treatment of ALK+NSCLC have made significant progress, in view of the With unique needs, effective treatment of ALK inhibitors is still a challenge. Alunbrig has been proven to be a potent inhibitor of ALK gene mutations, including in patients with brain metastases. The drug is approved in Japan, which is difficult for new diagnosis and treatment. Sexual ALK-positive NSCLC patients are an important milestone."

Christopher Arendt, head of Takeda's Oncology Department, said: “As a next-generation ALK inhibitor, Alunbrig has extensive clinical evidence to support it. It has been proven effective for ALK+NSCLC patients receiving first-line and second-line treatment, including the efficacy for patients with brain metastases. With Japan’s approval, we believe that in NSCLC caused by ALK driver gene mutations, more patients will be able to benefit from this targeted therapy."

Globally, lung cancer is one of the leading causes of cancer deaths. It is estimated that 1.8 million people are diagnosed with lung cancer every year. NSCLC is the most common type of lung cancer, accounting for approximately 85% of all lung cancer cases. ALK is the second therapeutic target found in NSCLC, and it exists in approximately 3%-5% of NSCLC patients, especially non-smoking young adenocarcinoma patients. The ALK gene of these patients often fused with other genes to produce ALK fusion protein. This mutation can lead to tumor growth.

Xalkori is the world's first ALK targeted therapy drug developed by Pfizer. The listing of this drug has greatly changed the clinical treatment of patients with advanced ALK+NSCLC, but the deterioration of the disease is often inevitable. When the tumor does not respond to Xalkori, patients rarely have treatment plan.

Alunbrig's active pharmaceutical ingredient is brigatinib, which is a potent, selective, next-generation ALK tyrosine kinase inhibitor (TKI) that can target ALK molecular changes and inhibit tumor growth. Brigatinib was discovered by Ariad Pharmaceuticals. Takeda acquired Ariad in February 2017 for US$5.2 billion.

Up to now, Alunbrig has been approved in more than 30 countries including the United States and the European Union: as a monotherapy, it is used to treat adults with ALK+ advanced NSCLC who have not previously been treated with ALK inhibitors. In addition, Alunbrig is also approved in more than 50 countries: it is used to treat adult patients with ALK+ metastatic NSCLC who have previously received crizotinib (crizotinib, brand name: Xalkori, Pfizer product) but have worsened or cannot tolerate crizotinib .

The approval of Alunbrig's single-agent first-line treatment indication is based on the results of the Phase III ALTA 1L study. The study was carried out in 275 patients with ALK+ locally advanced or metastatic NSCLC who had not previously been treated with ALK inhibitors, and compared the efficacy and safety of Alunbrig and Xalkori for first-line treatment. The median ages of the Alunbrig group and Xalkori group were 58 years and 60 years, respectively. The proportion of patients with brain metastases at baseline was 29% and 30%, respectively. The proportion of patients who had previously received chemotherapy for advanced or metastatic disease was 26. %, 27%. The main efficacy indicator of the study is the Progression-Free Survival (PFS) assessed by the blinded Independent Review Committee (BIRC). Other efficacy observation indicators include: the overall response rate evaluated according to the evaluation criteria for the efficacy of solid tumors (RECIST v1.1) ( ORR) and intracranial ORR.

After more than 2 years of follow-up, the results of the ALTA 1L study showed that Alunbrig is superior to Xalkori and has significant anti-tumor activity, especially in patients with brain metastases. Specific data show that according to the BICR assessment, after more than 2 years of follow-up: (1) In the entire study population (intention-to-treat [ITT] population), Alunbrig doubled the progression-free survival compared with Xalkori (median PFS) : 24 months vs 11.0 months), reduced the risk of disease progression or death by 51% (HR=0.49); in patients with baseline brain metastases, Alunbrig significantly reduced the risk of intracranial disease progression or death by 69% compared with Xalkori ( HR=0.31). (2) Compared with Xalkori, Alunbrig improved the overall response rate (ORR) in the entire study population (74%[95%CI:66-81] vs 62%[95%CI:53-70]); In patients with brain metastases, Alunbrig significantly improved intracranial ORR compared with Xalkori (78%[95%CI:52-94] vs 26%[95%CI:10-48]).