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Roche Abandons New Diabetes Drug Roche Stops Developing A New Drug For Diabetes
(about 2 hours later)
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, 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 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. 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 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. “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.
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.
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 rather 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 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. 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 developing similar drugs abandoned their efforts years ago after running into various safety problems. 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 conceivably play into the federal Food and Drug Administration’s deliberations over GlaxoSmithKline’s diabetes drug Avandia, which has a somewhat similar mechanism of action. 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.
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 cite the setback to Roche’s drug to argue for keeping the restrictions.
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. “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.
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. 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.
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. 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.
Despite these failures in cardiovascular drugs, investors in Roche typically care most about its main business of cancer drugs, including Avastin, Herceptin and Rituxan. 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.
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. Roche said on Wednesday that in light of the aleglitazar failure it would assess its role in cardiovascular and metabolic drugs.
Aleglitazar works by activating two receptors in the body, known as PPAR alpha and PPAR gamma. 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.
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. Aleglitazar works by activating two receptors, known as PPAR alpha and PPAR gamma.
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. Avandia activates mainly the gamma receptor, as does a similar diabetes drug, Actos by Takeda Pharmaceutical Company. Other drugs known as fibrates, which are used to lower triglycerides and raise good cholesterol, activate the alpha receptor.
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. Roche aimed for a drug that activated both receptors, hoping it would improve both blood lipids and blood sugar.
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. 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.
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. AstraZeneca and Bristol-Myers Squibb discontinued their drugs in 2006. Merck and Takeda gave up earlier.