Merck's Tredaptive fiasco blamed on adverse reactions to niacin

Two months ago Merck ($MRK) was forced to pull the plug on Tredaptive, a "good" cholesterol drug that foundered in a huge Phase III study after investigators tracked a number of nonfatal adverse events among the people taking the treatment, a combination of extended-release niacin and an experimental antiflushing drug called laropiprant. Initially, Merck didn't spell out the adverse events. But as regulators reacted with alarm in Europe, where it had been approved ahead of an FDA OK, the focus turned to the safety issues related to Tredaptive. 

Now a new study has detailed that a quarter of all the thousands of patients taking the drug had dropped out of the trial--compared to fewer than 17% in the placebo arm--mostly due to itching, rashes, indigestion and muscle problems. There were also dozens of serious reactions, including 29 cases of myopathy. And investigators pointed to niacin, a B vitamin, as the likely culprit.

"There's been a lot of interest in trying to find therapies to raise HDL," Dr. Erin Michos, a cardiologist at the Johns Hopkins School of Medicine in Baltimore, tells Reuters. "Unfortunately, I think there's a growing body of evidence that's going to put the nail in the coffin for niacin."

Ulf Landmesser, a Swiss investigator, also raised questions about laropiprant in a related editorial. He noted that the treatment is "really biologically inert with respect to atherosclerosis and thrombosis," according to a report in heartwire, adding that another study demonstrated signs of aneurysm formation and accelerated atherogenesis in mice "with deleted prostaglandin D2 receptors."

The problems with the combo were apparent at a very early stage. According to the Reuters report, investigators gave the treatment to 38,000 possible volunteers and found that a third opted out, typically because of the itching, rashes, indigestion and muscle problems that eventually scuttled the massive Phase III heart study that followed. Of those dropouts, 69 developed serious reactions, including 29 cases of myopathy.

The study, published in the European Heart Journal, also caused Oxford investigator Jane Armitage to give up on niacin, saying that "there's no role for adding niacin just to increase the HDL." But not everyone in the field is ready to follow.

"I continue to be baffled as to how the investigators can be so certain that this is niacin-related," Albany Medical College's William Boden told the news service. "We cannot simply, in my opinion, implicate one component of a combination drug over the other component."

Merck's failure with Tredaptive proved a serious setback in the pharma giant's late-stage drug-development campaign. The drug was one of five Phase III drugs that promised to deliver for Merck, which has been scrambling--largely ineffectively--at finding new therapies in the face of the patent cliff. Merck is releasing the full data from the study at the upcoming meeting of the American College of Cardiology.

- here's the Reuters report
- here's the story from heartwire (reg. req.)