Roche, the Swiss pharmaceutical giant, has discontinued development of a potentially important diabetes drug, a move that could raise new safety questions about the entire category of drugs, which includes the controversial diabetes medicine Avandia.
Roche said Wednesday that a safety monitoring committee had recommended halting a late-stage clinical trial of the drug, aleglitazar, because of “safety signals and lack of efficacy.” The company said that it decided to halt that study and all others involving the drug.
“We are disappointed by this outcome as we hoped that aleglitazar would provide significant benefit for patients with Type 2 diabetes who are at risk of cardiovascular disease,” Dr. Hal Barron, the chief medical officer, said in a statement.
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 not only diabetes but cardiovascular risk factors like cholesterol as well. 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 rather to see if it could prevent heart attacks and strokes in people with Type 2 diabetes.
A success would have been considered a major advance for diabetes because until now, 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 developing similar drugs abandoned their efforts years ago after running into various safety problems.
The failure of aleglitazar could conceivably play into the U.S. Food and Drug Administration’s deliberations over GlaxoSmithKline’s diabetes drug Avandia, which has a somewhat similar mechanism of action.
Avandia’s use was severely restricted in the United States and banned in Europe in 2010 because of concerns it could raise the risk of heart attacks and stroke. But an advisory committee to the F.D.A. recommended last month that the restrictions be eased. The agency itself has yet to make a decision.
Critics of Avandia could point to the setback to Roche’s drug to argue that the entire class of drugs is dangerous and that the restrictions on Avandia should remain in place.
However, while Roche’s statement indicated that aleglitazar did not lower the risk of heart attacks and strokes, it did not appear that the drug increased those risks, either, since the safety issues that ended trial were unrelated to heart attacks and strokes. Supporters of Avandia might say this offers more evidence that Avandia also does not raise cardiovascular risks.
Last year, Roche gave up on another potential blockbuster cardiovascular drug, dalcetrapib, which was aimed at increasing levels of so-called good cholesterol. In that case, a trial showed the drug did not work.
Despite these failures in cardiovascular drugs, investors in Roche typically care most about its main business of cancer drugs, including Avastin, Herceptin and Rituxan.
The study of aleglitazar involved more than 7,000 people with diabetes in numerous countries, all of whom had also suffered a recent heart attack or the onset or worsening of cardiac pain. The study was supposed to last five years, until around the beginning of 2015.
Aleglitazar works by activating two receptors in the body, known as PPAR alpha and PPAR gamma.
Avandia activates mainly the gamma receptor, as does a similar diabetes drug, Takeda’s Actos. Other drugs known as fibrates, which are used to lower triglycerides and raise good cholesterol, activate the alpha receptor.
Roche aimed for a drug that activated both receptors equally, hoping it would improve both blood lipids and blood sugar, and lower the extra cardiovascular risks that diabetics face.
But several other dual PPAR agonists, as the drugs are called, failed because of various safety issues years ago, leaving Roche perhaps the last big company pursuing that type of drug.
Previous failures included AstraZeneca’s Galida, which led to kidney problems, Merck’s MK-767, which produced tumors in mice, and Takeda’s TAK-559, which caused liver problems.
Bristol-Myers Squibb’s Pargluva was actually recommended for approval by an F.D.A. advisory committee in 2005. But shortly thereafter, Dr. Steven Nissen and other researchers at the Cleveland Clinic published an analysis showing that the drug might increase the risk of heart attacks and strokes. The F.D.A. also requested more safety data, and Bristol-Myers discontinued development.
Article source: http://www.nytimes.com/2013/07/11/business/roche-abandons-new-diabetes-drug.html?partner=rss&emc=rss