Roche, the Swiss pharmaceutical giant, has discontinued development of a potentially important diabetes drug, a move that could raise safety questions about the entire category of drugs, which includes the controversial medicine Avandia.
Roche said on Wednesday that an independent safety monitoring committee had recently recommended halting a late-stage clinical trial of the drug, aleglitazar, because of “safety signals and lack of efficacy.” The company said that it had decided to halt that study and all others involving the drug.
“We are very disappointed,” Dr. A. Michael Lincoff, the chairman of the study, said in an interview on Wednesday. A spokesman for the company, which is based in Basel, Switzerland, said the drug had caused an increase in fractures, kidney problems and heart failure in the trial.
Aleglitazar was designed to treat cardiovascular risk factors like cholesterol as well as diabetes. In a bold move, Roche was testing the drug not for its ability to lower blood sugar, the usual yardstick for a diabetes drug, but to see if it could prevent heart attacks and strokes in people with Type 2 diabetes.
Dr. Lincoff, who is vice chairman of cardiology at the Cleveland Clinic, said that, compared to a placebo, the drug neither raised nor lowered the risk of heart attacks, strokes or death from cardiovascular causes.
A successful test would have been considered a major advance against diabetes because better control of blood sugar has not generally been shown to lower the risk of heart attacks and strokes.
Still, it was, perhaps, a long shot. Many other companies abandoned efforts to develop similar drugs years ago after safety problems.
The failure of aleglitazar could influence the federal Food and Drug Administration’s deliberations over GlaxoSmithKline’s diabetes drug Avandia, which works similarly. Avandia was severely restricted in the United States and banned in Europe in 2010 because of fear it could raise the risk of heart attacks and strokes. But an advisory panel to the F.D.A. recommended last month that the restrictions be eased. The agency has yet to decide.
Critics of Avandia could cite the setback to Roche’s drug to argue for keeping the restrictions.
“I think it shows that the class of drugs has significant problems with toxicity, particularly cardiovascular toxicity,” Dr. Steven E. Nissen, the chairman of cardiovascular medicine at the Cleveland Clinic and a leading critic of Avandia, said Wednesday.
But since aleglitazar did not raise the risk of heart attacks and strokes, some supporters of Avandia might say that is more evidence that Avandia also does not raise cardiovascular risks.
The setback is the latest in Roche’s effort to diversify beyond its mainstay business of cancer drugs. Most of those drugs, including the blockbusters Avastin, Herceptin and Rituxan, were developed by Genentech, its California biotechnology subsidiary.
By contrast, Roche’s research operation based in Basel, which was responsible for aleglitazar, has had less success. Last year, another potential blockbuster, dalcetrapib, which was aimed at raising levels of so-called good cholesterol, failed in a late-stage clinical trial. In 2011, Roche dropped the diabetes drug taspoglutide because of side effects.
Roche said on Wednesday that in light of the aleglitazar failure it would assess its role in cardiovascular and metabolic drugs.
The study of aleglitazar involved more than 7,000 people with diabetes, all of whom had also had a recent heart attack or the onset or worsening of cardiac pain. The multinational study was supposed to last five years, until about the beginning of 2015.
Aleglitazar works by activating two receptors, known as PPAR alpha and PPAR gamma.
Avandia activates mainly the gamma receptor, as does a similar diabetes drug, Actos, from the Takeda Pharmaceutical Company. Other drugs known as fibrates, used to lower triglycerides and raise good cholesterol, activate the alpha receptor.
Roche aimed for a drug that activated both receptors, hoping it would improve both blood lipids and blood sugar.
But many other dual PPAR agonists, as the drugs are called, had failed years earlier because of safety issues, leaving Roche as perhaps the last big company still pursuing the category.
AstraZeneca and Bristol-Myers Squibb discontinued their drugs in 2006. Merck and Takeda gave up earlier.
Article source: http://www.nytimes.com/2013/07/11/business/roche-abandons-new-diabetes-drug.html?partner=rss&emc=rss