Genetic studies indicate that abnormal expression of ALK is a key driver of certain types of non-small cell lung cancer (NSCLC), neuroblastomas, and anaplastic large cell lymphoma (ALCL). Since ALK is generally not expressed in normal adult tissues, it represents a highly promising molecular target for cancer therapy.
ALK gene mutations are present in about five percent of NSCLCs1. ARIAD estimates that there are currently approximately 13,000 patients with Stage IV ALK+ NSCLC in the United States, Europe and Japan, based on healthcare information providers. As in other cancers, patients with ALK+ NSCLC can develop resistance or intolerance over time to approved treatments. ARIAD also estimates that there are approximately 6,000 patients with ALK+ NSCLC in the United States, Europe and Japan who annually develop resistance or intolerance to first-line tyrosine kinase inhibitor (TKI) treatment and who could be eligible for treatment with brigatinib, if it is approved for this indication.
To discover brigatinib, ARIAD scientists identified multiple compounds that potently inhibit ALK both in vitro and in vivo while maintaining significant selectivity over the highly homologous insulin-like growth factor-1 receptor and insulin receptor tyrosine kinases. Based on proprietary ARIAD chemistry, brigatinib was identified as the lead compound—in in-vitro studies it potently inhibited ALK-expressing tumor cells while having no effect on ALK-negative cells.
In 2010, ARIAD first announced results of preclinical studies on brigatinib showing potent inhibition of the target protein, including mutant forms that were resistant to the first-generation ALK inhibitor, crizotinib. ARIAD scientists presented these data at the annual meeting of the American Association for Cancer Research (AACR) in Washington, D.C. Read the Press Release.
ARIAD is investigating brigatinib in ALK+ NSCLC in ongoing clinical trials. More information can be found at brigatinib clinical trials page.
1 American Cancer Society