ARIAD Pharmaceuticals Inc. (ARIA) announced that it presented preclinical data on ponatinib or Iclusig, at the American Association for Cancer Research or AACR Annual Meeting 2013, in Washington. In separate studies, ponatinib is shown to potently inhibit RET, a clinically proven oncogenic driver of medullary thyroid cancer or MTC and non-small cell lung cancer or NSCLC, and FGFR, which is commonly mutated in endometrial, lung and other cancers.
According to the company, the first preclinical study, "Ponatinib is a highly-potent inhibitor of activated variants of RET found in MTC and NSCLC," shows that ponatinib inhibits naturally occurring activating mutants of RET found in MTC and NSCLC at clinically achievable plasma concentrations. The potency of ponatinib was found to substantially exceed that of other approved tyrosine kinase inhibitors with RET activity. These results provide strong support for the clinical evaluation of ponatinib in patients with RET-driven cancers, the company noted.
The company stated that the preclinical data strongly support moving forward with evaluating ponatinib in RET-positive cancers, and it looks forward to the start of a Phase 2 investigator-sponsored trial in patients with RET-positive NSCLC in this second quarter of 2013.
In the second preclinical study, "Ponatinib potently inhibits the activity of mutant variants of FGFR commonly found in endometrial, lung and other cancers," the ability of ponatinib to inhibit a broad panel of naturally occurring mutant variants of FGFR1, 2, 3, and 4 was evaluated.
Ponatinib potently blocked a variety of mutant variants of FGFR, with particularly promising activity against mutant variants of FGFR2 that have been observed in endometrial and squamous cell carcinomas or SCCs of the lung.
Specifically, ponatinib inhibits the eight mutants that make up more than 90 percent of the mutations observed in endometrial cancer patients, and six mutants observed in SCC at clinically achievable plasma concentrations. Ponatinib also shows encouraging activity against FGFR1/3 fusion proteins found in glioblastoma multiforme.
These data support clinical evaluation of ponatinib in FGFR-driven cancers, including a Phase 2 investigator-sponsored trial of ponatinib in patients with SCCs that is currently underway and enrolling patients, the company stated.
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