Fears over long QT. Credit: iStockphoto/Andrius Gruzdaitis

In a major setback for Amylin, the US Food and Drug Administration called for further tests on Amylin's Bydureon, a once-weekly drug for type 2 diabetes. On October 19, the San Diego-based biotech Amylin, and partner Eli Lilly of Indianapolis, announced that the agency had issued a Complete Response Letter calling for a study known as thorough QT to further investigate the potential effect of the drug's cardiac effects. Bydureon is a long-acting formulation of Amylin's approved drug Byetta (exenatide), an analog of the insulin-boosting glucagon-like peptide 1 (GLP-1) (Nat. Biotechnol. 28, 109, 2010). Both contain exenatide, but Bydureon contains a higher concentration of the active agent, delivered into the blood by controlled release. The first-in-class synthetic gut hormone drug Byetta generated $677 million in 2009 in the US alone. But Bydureon's formulation—once weekly injections compared with twice a day—is predicted to gain competitive edge over its predecessor if approved. Simos Simeonidis, managing director and senior biotech analyst at Rodman & Renshaw in New York, says that Bydureon had “blockbuster” potential and could have brought in at least $1 billion per year for Amylin after the first few years. The FDA's concerns over supratherapeutic concentrations of exenatide may have been triggered by observations in a Byetta study, in which a few patients with blood levels of 500 pg/ml had lengthened QT intervals. In patients with kidney problems, once-weekly Bydureon can reach five times the normal 200 pg/ml seen with Byetta. Given the delay in approving Bydureon, alternate treatments for type 2 diabetes like Victoza (liraglutide) from Novo Nordisk, of Princeton, New Jersey, and Amylin's own Byetta, are now expected to flourish. London-based GlaxoSmithKline's investigational Syncria(R) (albiglutide), also a GLP-1 analog, is currently undergoing phase 3 clinical trials. “They were considerably behind,” says Yaron Werber, senior biotech analyst at Citigroup in New York. “But now I think they have a chance to close a big part of the gap.”