Amylin, Lilly's Byetta May Have Cancer Risk, FDA Says

Data on intravenous dosing and a once-weekly version of Byetta "seem to give a similar signal" as cancers seen in rodent studies of Novo Nordisk A/S's competing Victoza, said Curtis Rosebraugh, head of the Food and Drug Administration's Office of Drug Evaluation II, in a Jan. 25 memo posted on the agency's website.

Victoza was approved in January after 10 months of delay because of safety concerns. During that review, the FDA said tumors may be common with all extended-release diabetes drugs in a family of medicines known as GLP-1 analogs, a class that includes Byetta and Victoza. The new memo is the first indication that long-acting Byetta will carry the same boxed warning, the agency's strictest caution, as Victoza.

When the long acting LAR version of Byetta gets approved by the FDA, there may be a similar black box warning about cancer and that is likely to dissuade some generalist physicians from adopting the long-acting GLP-1s, and therefore will make it somewhat harder for the class to achieve the growth that was assumed.

The FDA delayed a decision on a proposed once-weekly version of Byetta on March 15 and asked for more information on manufacturing, labeling and a risk-management plan. No new studies were ordered for the product, to be called Bydureon. Technology for the long-acting version was developed by Alkermes Inc., of Waltham, Massachusetts.

Novo Nordisk's Victoza, a daily shot chemically known as liraglutide, isn't recommended by the FDA as an initial treatment for diabetes. The FDA ordered the Bagsvaerd, Denmark-based company to conduct additional studies to assess a potential risk of thyroid tumors.

"Our internal data indicates that the preclinical findings are not unique to liraglutide but will probably extend to all" similar long-acting diabetes drugs, the FDA's Rosebraugh said in the memo included in Victoza's approval package. "So to condemn liraglutide would be to condemn them all."

Amylin said in a statement that the new report does not contain any new data on Byetta or Bydureon. The company noted that more than 1 million patients have used Byetta, with no signs of cancer.

Rats that received 25 times the human dose of Bydureon showed statistically significant risk of thyroid cancer, but the company said that result is "of uncertain significance to humans."

"A relationship between Bydureon and human thyroid cancer has not been established, but cannot be ruled out," the company said. "As is the case with any drug therapy, continued follow-up is warranted."

Victoza and Byetta belong to a class of diabetes medicines that imitate a hormone called GLP-1 to stimulate the pancreas to produce more insulin after meals.