U.S. FDA grants accelerated approval for Brigatinib
On April 28, 2017, the U.S. Food and Drug Administration granted accelerated approval to brigatinib (ALUNBRIG tablets, Takeda Pharmaceutical Company Limited, through its wholly owned subsidiary ARIAD Pharmaceuticals, Inc.) for the treatment of patients with metastatic anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC) who have progressed on or are intolerant to crizotinib.
Approval was based on a non-comparative, two-arm, open-label, multicenter clinical trial demonstrating a clinically meaningful and durable overall response rate (ORR) in patients with locally advanced or metastatic ALK-positive NSCLC who had progressed on crizotinib (the ALTA Trial; NCT02094573). All patients had tumors with a documented ALK rearrangement based on an FDA-approved test or a different test with adequate archival tissue to confirm ALK arrangement by the Vysis® ALK Break-Apart fluorescence in situ hybridization Probe Kit test. A total of 222 patients were randomized to brigatinib orally either 90 mg once daily (n=112) or 180 mg once daily following a 7-day lead-in at 90 mg once daily (n=110).
Safety was evaluated in 219 patients who received at least one dose of brigatinib in the ALTA trial. The most common adverse reactions, occurring in at least 25% of patients taking brigatinib, were nausea, diarrhea, fatigue, cough, and headache. The most common serious adverse reactions were pneumonia and ILD/pneumonitis. Fatal adverse reactions occurred in 3.7% of patients and consisted of pneumonia (2 patients), sudden death, dyspnea, respiratory failure, pulmonary embolism, bacterial meningitis and urosepsis (1 patient each). Visual disturbances also occurred in patients receiving brigatinib. Adverse reactions leading to permanent discontinuation of brigatinib occurred in 2.8% and 8.2% of patients receiving 90 mg and 180 mg, respectively.
Patients receiving brigatinib should be monitored for new or worsening respiratory symptoms, hypertension, bradycardia, visual symptoms, and elevations in amylase, lipase, blood glucose, and creatine phosphokinase.