Takeda's Next-Gen ALK Inhibitor Alunbrig Approved in Japan with Superior Efficacy Over Pfizer’s Xalkori in ALK+ NSCLC

January 28, 2021/Bio ValleyBIOON/-- Takeda Pharmaceutical Company Limited (Takeda) recently announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved the targeted anticancer drug Alunbrig (brigatinib, 30 mg, 90 mg, tablets) as a first-line and second-line treatment for patients with unresectable, advanced or recurrent anaplastic lymphoma kinase fusion gene-positive (ALK+) non-small cell lung cancer (NSCLC).

This approval was primarily based on the results of the Brigatinib-2001 (J-ALTA) Phase 2 study in Japan and the AP26113-13-301 (ALTA-1L) global Phase 3 study. The former study, conducted in Japan, involved 72 patients with unresectable advanced or recurrent ALK-positive non-small cell lung cancer (NSCLC) who had experienced disease progression after treatment with one ALK tyrosine kinase inhibitor (TKI). The latter study focused on patients with unresectable advanced or recurrent ALK-positive NSCLC who had not previously received ALK-TKI therapy.

J-ALTAClinical TrialChief Investigator, Department of Thoracic Surgery, Cancer Institute Hospital, Japanese Foundation for Cancer ResearchTumorMakoto Nishio, MD, stated: “Although significant progress has been made in the diagnosis, testing, and treatment of ALK-positive non-small cell lung cancer (NSCLC), effective treatment with ALK inhibitors remains a challenge given the unique needs of these patients. Alunbrig has been demonstrated to be a potent inhibitor of ALK gene mutations, including in patients with brain metastases. The approval of this drug in Japan marks a newDiagnosisRepresents an important milestone for patients with refractory ALK-positive NSCLC。”

TakedaTumorChristopher Arendt, Head of the Therapeutic Area Unit, stated, “As a next-generation ALK inhibitor, Alunbrig is supported by extensive clinical evidence and has demonstrated efficacy in patients with ALK-positive non-small cell lung cancer (NSCLC) receiving first-line and second-line treatment, including those with brain metastases. With its approval in Japan, we believe that more patients with NSCLC driven by ALK gene mutations will benefit from this targeted therapy.”

Globally, lung cancer is one of the leading causes of cancer-related deaths, with an estimated 1.8 million new diagnoses annually. Non-small cell lung cancer (NSCLC) is the most common type of lung cancer, accounting for approximately 85% of all cases. ALK is the second therapeutic target identified in NSCLC, present in about 3%–5% of patients, particularly in young, non-smoking individuals with adenocarcinoma. In these patients, the ALK gene often fuses with other genes to produce ALK fusion proteins; this mutation leads toTumorGrowth.

Xalkori is manufactured byPfizerThe world’s first ALK-targeted therapy developed, the launch of which has significantly transformed the clinical management of patients with advanced ALK+ NSCLC; however, disease progression is often inevitable, whenTumorFew Treatment Options Remain for Patients After Non-Response to Xalkori

The active pharmaceutical ingredient of Alunbrig is brigatinib, a potent, selective, next-generation ALK tyrosine kinase inhibitor (TKI) that targets ALK molecular alterations and inhibitsTumorGrowth. Brigatinib was discovered by Ariad Pharmaceuticals, and Takeda acquired this product by purchasing Ariad for $5.2 billion in February 2017.

To date, Alunbrig has been approved in more than 30 countries, including the United States and the European Union, as a monotherapy for the treatment of adult patients with ALK-positive advanced non-small cell lung cancer (NSCLC) who have not previously received an ALK inhibitor. In addition, Alunbrig has been approved in more than 50 countries for the treatment of adult patients with ALK-positive metastatic NSCLC who have previously been treated with crizotinib (brand name: Xalkori, a Pfizer product) and whose disease has progressed or who are intolerant to crizotinib.

The approval of Alunbrig as monotherapy for first-line treatment indications is based on the results of the Phase III ALTA 1L study. This study was conducted in 275 patients with ALK-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) who had not previously received ALK inhibitor therapy, comparing the efficacy and safety of Alunbrig versus Xalkori for first-line treatment. The median ages were 58 years in the Alunbrig group and 60 years in the Xalkori group; the proportions of patients with brain metastases at baseline were 29% and 30%, respectively; and the proportions of patients who had previously received chemotherapy for advanced or metastatic disease were 26% and 27%, respectively. The primary efficacy endpoint was progression-free survival (PFS) assessed by a Blinded Independent Review Committee (BIRC). Other efficacy endpoints included overall response rate (ORR) and intracranial ORR evaluated according to the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).

After more than 2 years of follow-up, the results of the ALTA 1L study showed that Alunbrig was superior to Xalkori, with significant anti-Tumoractivity, particularly in patients with brain metastases. Specific data show that, based on BICR assessment and after more than 2 years of follow-up: (1) in the overall study population (intent-to-treat [ITT] population),Alunbrig Doubles Progression-Free Survival Compared with Xalkori(median PFS: 24 months vs. 11.0 months),Reduce 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) In the entire study population,Alunbrig increases the overall response rate (ORR) compared to Xalkori(74% [95% CI: 66–81] vs. 62% [95% CI: 53–70]); in patients with baseline brain metastases,Alunbrig Significantly Improves Intracranial ORR Compared with Xalkori(78% [95% CI: 52–94] vs. 26% [95% CI: 10–48]). (Bioon.com)

Original Source: Manufacturing and Marketingapproval Received in Japan for ALUNBRIG® in the Treatment of ALK Fusion Gene-positive Unresectable Advanced or Recurrent Non-Small Cell Lung Cancer