FDA Accelerated Approval Announcement
Cambridge, Mass. and Osaka, Japan – April 28, 2017 – Takeda Pharmaceutical Company Limited (TSE: 4502) today announced that Alunbrig (brigatinib) has received Accelerated Approval from the U.S. Food and Drug Administration (FDA) for the treatment of patients with anaplastic lymphoma kinase-positive (ALK+) metastatic non-small cell lung cancer (NSCLC) 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. Alunbrig, which previously received Breakthrough Therapy Designation from the FDA, is a once-daily oral therapy that may be taken with or without food.
Expert Commentary on Clinical Significance
“In recent years, small molecule ALK inhibitors have revolutionized the treatment options for those with advanced ALK+ non-small cell lung cancer. Nevertheless, there is still a need for additional ALK inhibitors like brigatinib (Alunbrig), which have a manageable safety profile and may address mechanisms of clinical resistance to crizotinib, including progression in the central nervous system,” said D. Ross Camidge, M.D., Ph.D., Director of Thoracic Oncology at the University of Colorado. “The ALTA trial showed that brigatinib (Alunbrig) was highly effective post-crizotinib, with the majority of patients who received 180 mg once daily (with a seven-day lead-in at 90 mg once daily) achieving an overall response and a median duration of response greater than one year. Importantly, the extent of activity among those with brain metastases was also notable.”
Patient Advocacy Perspective
“For patients with ALK+ metastatic NSCLC who have progressed on or are intolerant to crizotinib, facing the uncertainty of disease progression and the potentially devastating impact of brain metastases, the approval of Alunbrig offers new hope,” said Bonnie Addario, Founder and Chair of the Addario Lung Cancer Foundation (ALCF).
Takeda Leadership Statements
“The rapid development of Alunbrig is a tribute to the dedication of many research scientists and clinicians who carefully designed and developed this new medicine to address unmet medical needs in the ALK+ NSCLC patient population. Most importantly, we would like to thank the patients and families who participated in the clinical trials,” said Andy Plump, M.D., Ph.D., Takeda Chief Medical and Scientific Officer.
“Today’s FDA approval of Alunbrig is an important milestone in the treatment of patients with ALK+ metastatic NSCLC who have progressed on or are intolerant to crizotinib,” said Christophe Bianchi, M.D., President of Takeda Oncology. “Takeda is committed to the continued development of Alunbrig around the globe and to bringing this important therapy to more patients in need.”
About the Pivotal Phase 2 ALTA Trial
The FDA approval of Alunbrig was primarily based on results from the pivotal Phase 2 ALTA (ALK in Lung Cancer Trial of AP26113) trial of brigatinib in adults. This ongoing, two-arm, open-label, multicenter trial enrolled 222 patients with locally advanced or metastatic ALK+ NSCLC who had progressed on crizotinib.
Trial Design
Patients were randomized to receive either:
90 mg of Alunbrig once daily (n=112), or
180 mg once daily following a seven-day lead-in period of 90 mg once daily (n=110).
Key Efficacy Endpoints
The primary efficacy outcome measure was confirmed overall response rate (ORR) according to Response Evaluation Criteria in Solid Tumors (RECIST v1.1), as assessed by an Independent Review Committee (IRC).
Additional efficacy outcome measures included:
Investigator-assessed ORR
Duration of response (DOR)
Intracranial ORR
Intracranial DOR
