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Jan 18, 2010
 |  BioCentury  |  Product Development

Differentiating EGFR inhibitors

Anti-EGFR drugs for non-small cell lung cancer have been on the market for seven years, but the factors that drive patient response and acquired resistance are still poorly understood. New research presented last week shows that EGFR inhibitors on the market and in development have different propensities for succumbing to resistance due to a specific mutation that accounts for about half of acquired resistance.

Symphony Evolution Inc. believes the data suggest its XL647 could be used prior to other EGFR inhibitors. The company, which was formed by Symphony Capital LLC in 2005 to develop compounds from Exelixis Inc., is looking for a partner to finance Phase III trials.

Two EGFR inhibitors are marketed for NSCLC: Tarceva erlotinib is approved worldwide for second- or third-line treatment, and Iressa gefitinib is approved outside the U.S. for use in patients with EGFR-activating mutations.

Tarceva, which is marketed by OSI Pharmaceuticals Inc., Roche, and Roche's Genentech Inc. unit, posted $1.2 billion in worldwide sales in FY09. In October, AstraZeneca plc reported nine-month sales of $218 million for Iressa.

These first-generation drugs work best in patients with activating mutations in the tyrosine kinase domain of EGFR, which are present in 30-50% of East Asian patients and 10-15% of patients in North America and Western Europe.

Research suggests that the activating mutations increase the ability of tumor cells to proliferate and survive, but the same signal that drives those gains also makes the cancer cells more sensitive to EGFR inhibitors.

All NSCLC patients who initially respond to one of the marketed EGFR inhibitors will eventually develop resistance, with roughly half of patients with activating mutations...

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