cardiovascular causes

Roche Stops Developing a New Drug for Diabetes

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

AstraZeneca Anticlotting Drug Wins Approval

The Food and Drug Administration on Wednesday approved Brilinta, a new blood thinner from AstraZeneca that the company hopes can rival Plavix, the No. 2 best-selling drug in the world.

The agency will require a boxed warning about how the drug’s effectiveness will be reduced if it is taken with higher doses of aspirin. But the approved label — critical to marketing the drug — also says Brilinta was proved superior to Plavix in reducing heart attacks and deaths from cardiovascular causes.

“It’s good news for patients, and it’s a good result for AstraZeneca as well,” said Dr. Alex Gold, the company’s brand development leader. “We think the label has been a good outcome and will enable physicians to use the drug appropriately.”

The F.D.A. opened the United States market to Brilinta — already approved in 38 other countries — while also imposing a monitoring program to require AstraZeneca to inform physicians of the aspirin risk.

The agency’s move followed the rejection on Tuesday of another AstraZeneca drug, dapagliflozin, an experimental diabetes drug that an F.D.A. advisory panel decided in a 9-6 vote carried too high a risk of bladder and breast cancer. The F.D.A. usually but not always follows its advisory panel advice.

The blood drug Brilinta had also been under tough scrutiny by the F.D.A., analysts said, because test results in an industry-sponsored clinical trial were far worse among patients in the United States than those from the rest of the world for reasons that remain unclear.

In December, the F.D.A. rejected Brilinta in a surprising move, opposing the views of a scientific advisory panel that had voted 7-1 in favor of the drug in July 2010. The F.D.A. asked for and received more information from AstraZeneca.

In a note to investors, Timothy Anderson, analyst for Bernstein Research, said he continued to believe commercial prospects would be limited because of the pending lower prices for Plavix. The aspirin warning may be significant, he said. “It may give physicians one more reason not to use Brilinta but to stick to gold-standard Plavix.”

Brilinta also has a boxed warning about bleeding risk that also applies to other antiplatelet agents, such as Plavix. Another side effect of Brilinta, but not Plavix, is difficulty breathing in some cases. Brilinta is the latest attempt by pharmaceutical companies to outdo Plavix in the lucrative market for a pill to prevent strokes and heart attacks in coronary patients. The F.D.A. in 2009 approved a new blood thinner called Effient from Daiichi Sankyo and Eli Lilly. But it attached a black-box warning about excessive bleeding, and sales have fallen short of expectations.

Plavix was the second-best-selling drug in the world last year behind Lipitor, a cholesterol drug from Pfizer. The patent for Plavix, held by Sanofi Aventis and Bristol-Myers Squibb, expires in May 2012, and should lead to lower prices that may make Plavix more attractive as doctors and insurers weigh the costs, risks and benefits of new drugs.

In Europe, where generic forms of Plavix have been available since 2009, the low generic prices have stalled sales of the European version of Brilinta, called Brilique. It was approved by the European Union last year based on a study of 18,624 coronary patients in 43 countries.

The study, paid for by AstraZeneca, compared Brilinta and aspirin head-to-head with Plavix and aspirin. It found 16 percent fewer deaths, heart attacks and strokes in a year among Brilinta patients, with no more bleeding problems. But paradoxically, the results were opposite that among the 1,400 Americans in the trial. They had a higher rate of negative outcomes, a figure that was not statistically significant over all because of the lower number of patients, but that certainly caught regulators’ attention.

AstraZeneca has attributed the difference to higher aspirin dosing in the United States. The F.D.A. accepted that reasoning in the boxed label warning that says more than 100 milligrams a day of aspirin would “reduce the effectiveness of Brilinta and should be avoided,” but lower doses were recommended.

Brilinta prevents blood platelets from sticking together and forming clots. It is faster-acting than Plavix and reversible if the patient bleeds. Some patients respond to Brilinta who do not respond to Plavix, for genetic reasons.

Article source: http://feeds.nytimes.com/click.phdo?i=84d1fb04ba13c6b14f798c97601fba45

Roche Stops Developing a New Drug for Diabetes

AstraZeneca Anticlotting Drug Wins Approval

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