ARIAD Pharmaceuticals, Inc. announced results of preclinical studies on its investigational anaplastic lymphoma kinase (ALK) inhibitor, AP26113, showing that AP26113 has a novel profile as a dual inhibitor of ALK and epidermal growth factor receptor (EGFR), an additional validated target in non-small cell lung cancer (NSCLC). In addition to inhibition of ALK and its mutant forms, AP26113 was shown to inhibit the EGFR T790M mutant that is resistant to available EGFR inhibitors.
Resistant forms of EGFR-mutant lung cancer represent a large unmet medical need with no available therapies. ARIAD will be filing the IND for AP26113 this month and look forward to moving AP26113 into a Phase 1/2 clinical trial in the third quarter of 2011.
Activating mutations in EGFR are found in approximately 10 percent of NSCLC in Western populations and 30 percent of Asian NSCLC patients. The clinical utility of first-generation EGFR inhibitors, such as erlotinib, is limited by the development of resistance, linked in about 50 percent of patients to the emergence of the T790M “gatekeeper” mutation. This represents a potential target patient population of 125,000 resistant NSCLC patients globally, in addition to another 40,000 patients with ALK-positive NSCLC. Second-generation EGFR inhibitors targeting T790M are in development, but clinical efficacy has been limited due to toxicity related to the co-inhibition of native (unactivated) EGFR.
Preclinical studies show that AP26113 potently inhibited activated EGFR or its T790M mutant, both in cell culture and in mouse tumor models following once daily oral dosing. Importantly, the effective oral doses in these preclinical models were similar to those previously shown to be effective in resistant ALK models. When tested against the native form of EGFR, AP26113 lacked activity, indicating a favorable selectivity for activated EGFR.
“The EGFR inhibitory activity of AP26113 substantially changes its profile, significantly expanding the potential target patient population and commercial value of this tyrosine kinase inhibitor,” stated Timothy P. Clackson, Ph.D., president of research and development and chief scientific officer at ARIAD. “Resistant forms of EGFR-mutant lung cancer represent a large unmet medical need with no available therapies. We will be filing the IND for AP26113 this month and look forward to moving AP26113 into a Phase 1/2 clinical trial in the third quarter of this year.”
Date: June 16, 2011
Source: ARIAD Pharmaceuticals, Inc.
Filed Under: Drug Discovery