European Commission Approves ALUNBRIG® (brigatinib) for ALK+ Non-Small Cell Lung Cancer in Patients Previously Treated with Crizotinib, Advancing Treatment Paradigm in Europe

- ALUNBRIG Demonstrated Unprecedented Median Progression-Free Survival of 16.7 Months and Overall Survival of 34.1 Months in the Post-Crizotinib Setting 

- Approval Will Help Address Current Unmet Need in ALK+ NSCLC Treatment in the EU, Building Upon Approvals in the U.S. and Canada

CAMBRIDGE, MA, USA and OSAKA, Japan I November 27, 2018 I Takeda Pharmaceutical Company Limited (TSE: 4502) today announced that the European Commission (EC) granted marketing authorization for ALUNBRIG (brigatinib) as a monotherapy for the treatment of adult patients with anaplastic lymphoma kinase-positive (ALK+) advanced non-small cell lung cancer (NSCLC) previously treated with crizotinib. The decision follows a positive opinion from the Committee for Medicinal Products for Human Use (CHMP) on September 20, 2018.

“The introduction of targeted therapies has greatly improved the treatment of ALK+ NSCLC, yet for the approximately 70 percent of patients who progress on crizotinib with brain metastases, additional therapeutic options are needed,” said Enriqueta Felip, M.D., PhD., Head of the Thoracic Oncology Unit, Oncology Department at Vall d’Hebron University Hospital in Barcelona. “Data from the ALTA trial investigating ALUNBRIG showed sustained systemic and intracranial efficacy results and a manageable safety profile, leading to the longest progression-free survival and overall survival reported in this setting. This approval gives physicians in the European Union another choice in addressing ALK+ NSCLC patients previously treated with crizotinib.”

“The European Commission’s decision to approve ALUNBRIG for patients with ALK+ NSCLC is a significant advancement for European patients impacted by this life-threatening disease,” said Jesús Gómez-Navarro, M.D., Vice President, Head of Oncology Clinical Research and Development, Takeda. “This is the first time a median progression-free survival of over 16 months as assessed by an independent review committee and median overall survival of 34 months have been reported in the post-crizotinib setting, which highlights the strength of the ALTA trial data. The authorization of ALUNBRIG in the EU speaks to our ongoing commitment to developing innovative solutions to improve the lives of the approximately 40,000 patients diagnosed with this disease worldwide each year.”

“Many people are unaware of ALK+ NSCLC and its nuances, including the fact this type of lung cancer tends to affect people at a younger age, and it is not associated with smoking,” said Stefania Vallone, President, Lung Cancer Europe. “These younger patients are often in the prime of their lives and in the middle of raising their families, focusing on their careers, and contributing to their community. The availability of new treatments to potentially extend time without disease progression is very important and cannot be underestimated.”

The European Commission’s approval is based on data from the global Phase 2 ALTA trial, in which patients were randomized to receive one of two dosing regimens of ALUNBRIG: 90 mg once daily (n=112) or the recommended dosing regimen of 180 mg once daily with seven-day lead-in at 90 mg once daily (n=110). Results showed that of the patients who received the recommended dosing regimen, 56 percent achieved an objective response rate (ORR), and the median duration of response (DOR) was 15.7 months as assessed by independent review committee (IRC). ALUNBRIG demonstrated a median progression-free survival (PFS) of 16.7 months by IRC assessment and overall survival of 34.1 months for patients with locally advanced or metastatic ALK+ NSCLC who had progressed on crizotinib.

The most common adverse reactions (≥25%) reported in patients treated with ALUNBRIG at the recommended 180 mg dosing regimen were increased aspartate aminotransferase (AST), hyperglycemia, hyperinsulinemia, anemia, increased creatine phosphokinase (CPK), nausea, increased lipase, decreased lymphocyte count, increased alanine aminotransferase (ALT), diarrhea, increased amylase, fatigue, cough, headache, increased alkaline phosphatase, hypophosphatemia, increased abnormal activated partial thromboplastin time (APTT), rash, vomiting, dyspnea, hypertension, decreased blood cell count, myalgia, and peripheral neuropathy. The most common serious adverse reactions (≥ 2 percent) reported in patients treated with ALUNBRIG at the recommended dosing regimen other than events related to neoplasm progression were pneumonitis, pneumonia, and dyspnea.  

This decision by the European Commission means that ALUNBRIG is now approved for marketing of this indication in the 28 member states of the European Union, and applicable in Norway, Liechtenstein and Iceland. For further details about the European Commission decision, please visit the European Medicines Agency website: www.ema.europe.eu/ema.

About the ALTA Trial

The Phase 2 ALTA (ALK in Lung Cancer Trial of AP26113) trial of ALUNBRIG in adults is a global, ongoing, two-arm, open-label, multicenter trial, which enrolled 222 patients with locally advanced or metastatic ALK+ NSCLC who had progressed on crizotinib. Patients received either 90 mg of ALUNBRIG once daily (n=112) or 180 mg once daily with seven-day lead-in at 90 mg once daily regimen (n=110). Investigator-assessed confirmed objective response rate (ORR) per RECIST v1.1 was the primary endpoint. Key additional endpoints included Independent Review Committee (IRC)-assessed ORR, duration of response (DOR), progression-free survival (PFS), intracranial ORR, intracranial DOR, safety and tolerability.

Results of the ALTA trial demonstrated that of the patients who received the 180 mg dosing regimen, 56 percent achieved an ORR as assessed by investigator and 56 percent as assessed by IRC. The median DOR was 13.8 months as assessed by investigator and 15.7 months by IRC assessment. Median PFS was 15.6 months as assessed by investigator and 16.7 months by IRC assessment. Additionally, of the patients with measurable brain metastases at baseline (n=18), 67 percent achieved an intracranial ORR by IRC assessment; median duration of intracranial response was 16.6 months by IRC assessment. Median overall survival was 34.1 months.

Among patients who received the 90 mg dosing regimen, 46 percent achieved an ORR as assessed by investigator and 51 percent as assessed by IRC. The median DOR was 12.0 months as assessed by investigator and 16.4 months by IRC assessment. Median PFS was 9.2 months as assessed by both investigator and IRC assessment. Additionally, of the patients with measurable brain metastases at baseline (n=26), 50 percent achieved an intracranial ORR by IRC assessment; median duration of intracranial response was 9.4 months by IRC assessment. Median overall survival was 29.5 months.

About ALK+ NSCLC

Non-small cell lung cancer (NSCLC) is the most common form of lung cancer, accounting for approximately 85 percent of the estimated 1.8 million new cases of lung cancer diagnosed each year worldwide, according to the World Health Organization. Genetic studies indicate that chromosomal rearrangements in anaplastic lymphoma kinase (ALK) are key drivers in a subset of NSCLC patients. Approximately three to five percent of patients with metastatic NSCLC have a rearrangement in the ALK gene.

Takeda is committed to continuing research and development in NSCLC to improve the lives of the approximately 40,000 patients diagnosed with this serious and rare form of lung cancer worldwide each year.

About ALUNBRIG® (brigatinib)

ALUNBRIG is a targeted cancer medicine discovered by ARIAD Pharmaceuticals, Inc., which was acquired by Takeda in February 2017. In April 2017, ALUNBRIG received Accelerated Approval from the U.S. Food and Drug Administration (FDA) for ALK+ metastatic NSCLC patients who have progressed on or are intolerant to crizotinib. This indication is approved under Accelerated Approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. In July 2018, Health Canada approved ALUNBRIG for the treatment of adult patients with ALK+ metastatic NSCLC who have progressed on or who were intolerant to an ALK inhibitor (crizotinib). The FDA and Health Canada approvals of ALUNBRIG were primarily based on results from the pivotal Phase 2 ALTA (ALK in Lung Cancer Trial of AP26113) trial. 

ALUNBRIG received Breakthrough Therapy Designation from the FDA for the treatment of patients with ALK+ NSCLC whose tumors are resistant to crizotinib and was granted Orphan Drug Designation by the FDA for the treatment of ALK+ NSCLC, ROS1+ and EGFR+ NSCLC.

The brigatinib clinical development program further reinforces Takeda’s ongoing commitment to developing innovative therapies for people living with ALK+ NSCLC worldwide and the healthcare professionals who treat them. The comprehensive program includes the following clinical trials: 

  • Phase 1/2 trial, which was designed to evaluate the safety, tolerability, pharmacokinetics and preliminary anti-tumor activity of ALUNBRIG
  • Pivotal Phase 2 ALTA trial investigating the efficacy and safety of ALUNBRIG at two dosing regimens in patients with ALK+ locally advanced or metastatic NSCLC who had progressed on crizotinib
  • Phase 3 ALTA-1L, a global randomized trial assessing the efficacy and safety of ALUNBRIG in comparison to crizotinib in patients with ALK+ locally advanced or metastatic NSCLC who have not received prior treatment with an ALK inhibitor
  • Phase 2 single-arm, multicenter trial in Japanese patients with ALK+ NSCLC, focusing on patients who have progressed on alectinib
  • Phase 2 global, single arm trial evaluating ALUNBRIG in patients with advanced ALK+ NSCLC who have progressed on alectinib or ceritinib
  • Phase 3 global randomized trial comparing the efficacy and safety of ALUNBRIG versus alectinib in participants with ALK+ NSCLC who have progressed on crizotinib

For additional information on the brigatinib clinical trials, please visit www.clinicaltrials.gov.

About Takeda Pharmaceutical Company

Takeda Pharmaceutical Company Limited is a global, research and development-driven pharmaceutical company committed to bringing better health and a brighter future to patients by translating science into life-changing medicines. Takeda focuses its R&D efforts on oncology, gastroenterology and central nervous system therapeutic areas plus vaccines. Takeda conducts R&D both internally and with partners to stay at the leading edge of innovation. New innovative products, especially in oncology and gastroenterology, as well as our presence in Emerging Markets, fuel the growth of Takeda. More than 30,000 Takeda employees are committed to improving quality of life for patients, working with our partners in health care in more than 70 countries. For more information, visit http://www.takeda.com/news.

Additional information about Takeda is available through its corporate website, www.takeda.com, and additional information about Takeda Oncology, the brand for the global oncology business unit of Takeda Pharmaceutical Company Limited, is available through its website, www.takedaoncology.com.

SOURCE: Takeda Pharmaceutical Co

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