FDA Ponders Stricter Rules For Diabetes Drugs

-Forbes

03/04/2008 - In the wake of the controversy over the diabetes drug Avandia, the U.S. Food and Drug Administration is considering tougher standards for how and when diabetes drugs will be tested for risks to the heart.

Two drug safety advocates who played a key role in the debate over Avandia, made by drug giant GlaxoSmithKline, praised the draft results that were circulated by the FDA Feb. 29. (See full document at fda.gov.)

Investors got a taste of the downside of the new regulations as shares of Amylin Pharmaceuticals, a maker of diabetes drugs, fell to a 30-month low after a financial analyst speculated that the new guidance could slow up the approval of a key drug.

Last May, Steven Nissen, head of cardiology at the Cleveland Clinic, wrote an article in The New England Journal of Medicine saying that Avandia increased the risk of heart attacks and strokes by 40%. Glaxo took issue with Nissen's methodology, but Avandia sales plummeted anyway. The drug got stuck with a warning about heart attacks that its main competitor, Takeda Pharmaceutical's Actos, does not carry.

Glaxo continues to stand behind Avandia's safety and efficacy. But Nissen and others critics say the company waited too long to start trials to prove that Avandia's blood-sugar-lowering potential translated into benefits for patients.

Nissen calls the new guidance "a definite step in the right direction." He calls it a "compromise" between insisting that all the data are available when a medicine is approved, which might make drug development so expensive that new treatments would never make it to market, and the current situation: not having big studies start until years after a medicine hits pharmacy shelves, if ever.

An FDA spokeswoman said the guidance did not result from the controversy, but other sources interviewed for this article disagreed.

Clifford Rosen, a researcher at the Jackson Laboratory in Bar Harbor, Maine, who headed up an FDA advisory panel on Avandia's heart risk, says he is "encouraged" by the new guidance. He says that too often big studies to prove that drugs prevent hard outcomes like heart attacks or death are started too slowly.

"It is setting the stage for some harder times for diabetes drugs," Rosen admits. He sees the message to drug companies as "be careful," because measures of blood sugar alone won't be enough to get some medicines approved.

One drug Rosen doesn't see being tarred by the guidance is the long-acting form of Byetta, a diabetes injection sold by Amylin and Eli Lilly. The main putative side effect for that drug is pancreatitis, and the concern is based mainly on case reports.

But Matthew Osborne, an analyst at Lazard Capital Markets, downgraded Amylin to "hold" from "buy" because of the draft guidance. He wants more clarity on whether changes in the FDA's thinking could hurt Amylin before he recommends the stock.

"What substantiates a safety concern is not always clear," Osborne says. He thinks there is at least a theoretical concern that a "safety first" environment could delay Amylin's filing of a new drug application for the long-acting Byetta toward the middle of 2009, as Wall Street expects. He notes that the worries come at a time when biotech investors are increasingly risk averse.

But even if Amylin's drug emerges unscathed, drug development in diabetes looks to get tougher--and it was already tough. A few years ago, Merck, Bristol-Myers Squibb and AstraZeneca were all developing medicines that attempted to improve on Avandia. All of them turned out to be toxic, and the programs were scratched.

If you or a loved one have experienced an Avandia heart attack, or Avandia stroke, Avandia congestive heart failure, Avandia cardiovascular disease or if you have lost a loved one to an Avandia death you may be entitled to compensation. Contact the Avandia attorneys of Ennis & Ennis today for a free confidential case evaluation. Our on staff nurse and lawyers are standing by to answer any questions you may have regarding Avandia's side effects, a possible Avandia class action lawsuit, or any other type of Avandia litigation.