The recent first global approval of brigatinib has been reviewed in detail in the First Global Approval report in Adis journal Drugs, based on the development milestones tracked in AdisInsight.

In April 2017, brigatinib (ALUNBRIG™), developed by ARIAD Pharmaceuticals (a wholly-owned subsidiary of Takeda), received its first (and accelerated) global approval in the US for treatment of patients with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) who have progressed or who are intolerant to crizotinib.[1]

Brigatinib is an oral tyrosine kinase inhibitor that inhibits ALK, ROS1 and epidermal growth factor receptor (EGFR): AKL is associated with brain development under normal conditions, but when abnormally expressed, it is a driver for the development of NSCLC. Both ROS1 and EGFR are validated targets for the treatment of NSCLC,  however, mutant EGFR is responsible for treatment-resistance in half of EGFR-positive lung cancers; brigatinib inhibits this mutation.

The American Cancer Society forecasts an approximate 222,500 new cases of lung cancer for 2017 in the US; 85% of which are most likely to be NSCLC.[2]

Brigatinib, a 2nd generation ALK inhibitor, is designed to avoid drug resistance that has been evident within 8 months of initiating crizotinib therapy[3]. It has been granted Orphan Drug and Breakthrough Therapy Designations and was approved via the Accelerated Approval Process. As such, the continued approval of brigatinib in this indication may be conditional on ARIAD confirming clinical efficacy and benefit in an additional trial.[1]

“In recent years, small molecule ALK inhibitors have revolutionized the treatment options for those with advanced ALK+ non-small cell lung cancer,” said D. Ross Camidge, M.D., Ph.D., director of thoracic oncology at the University of Colorado. He continued by explaining that, “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.“[4]

Bonnie Addario, founder and chair of the Addario Lung Cancer Foundation (ALCF) spoke of the “new hope” that the approval of brigatinib offered to patients with progressed or crizotinib-resistant disease “who are facing the uncertainty of disease progression and the potentially devastating impact of brain metastases.” [4]

Brigatinib is currently under regulatory review for Marketing Authorisation in the EU as second-line therapy in patients with NSCLC. The agent is also under phase III investigations globally as first-line therapy in late stage NSCLC.

The FDA advise that patients receiving brigatinib should be monitored for new or worsening respiratory symptoms, hypertension, bradycardia, visual symptoms, as well as elevated levels of amylase, lipase, blood glucose, and creatine phosphokinase.[1]

For further information related to the first approval of brigatinib please visit Drugs or to learn more about the overall development of brigatinib across all indications visit AdisInsight.

Image credit:  magicmine /

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