Date: 2015-04-21
Type of information: Presentation of results at a congress
phase: preclinical
Announcement: presentation of results at the American Association for Cancer Research (AACR) Annual Meeting
Company: Ariad Pharmaceuticals (USA - MA)
Product: brigatinib (AP26113)
Action
mechanism: kinase inhibitor/tyrosine kinase inhibitor.
Disease:
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On April 21, 2015, Ariad Pharmaceuticals announced the results of a series of preclinical studies on its investigational tyrosine kinase inhibitor (TKI), brigatinib (AP26113) at the American Association for Cancer Research (AACR) Annual Meeting 2015. Brigatinib is in development for the treatment of patients with anaplastic lymphoma kinase positive (ALK+) metastatic non-small cell lung cancer (NSCLC), who are resistant to crizotinib.
These data were included in two presentations: "Discovery of AP26113, a potent, orally active inhibitor of anaplastic lymphoma kinase and clinically relevant mutants" and "The potent ALK inhibitor AP26113 can overcome mechanisms of resistance to first and second-generation ALK TKIs in preclinical models."
Oral Presentation on Brigatinib Discovery: An oral presentation describes, for the first time, the design and chemical structure of brigatinib, discovered using Ariad's structure-based drug design platform. With the goal of designing a selective ALK inhibitor with broad-based activity against crizotinib-resistant mutants, Ariad scientists advanced a series of novel compounds culminating in the identification of brigatinib. Brigatinib incorporates unique chemical-design features, including the distinctive use of a recognition element that confers favorable pharmacologic properties. Brigatinib has at least 10-fold greater potency than crizotinib against ALK+ NSCLC cell lines and was broadly active against clinically relevant crizotinib-resistant mutants in preclinical models.
New Preclinical Data on Brigatinib in Poster Presentation: A poster presentation shows that brigatinib, at clinically achievable concentrations, has potent anti-tumor activity against a panel of 17 distinct ALK mutants known to confer resistance to other ALK inhibitors. In a separate study designed to model the occurrence of brain metastases in ALK+ lung cancer patients, brigatinib significantly reduced the tumor burden in mice with ALK+ brain tumors compared to the tumors in mice treated with crizotinib. Survival of brigatinib-treated mice was also markedly enhanced compared to the survival duration of crizotinib-treated mice.
