June 23, 2021

Roche Abandons New Diabetes Drug

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

Wall Street Indexes Try to Find Their Footing

Caterpillar , the Chevron Corporation and Merck Company each beat earnings forecasts for the first-quarter. Merck, the pharmaceutical giant, said its profit more than tripled because of much lower restructuring and merger costs.

Caterpillar, the world’s largest maker of mining and construction equipment, rose 2.25 percent in early trading after the company said its earnings rose more than fivefold. The company also raised its sales and profit outlook for the year. Caterpillar is closely watched on Wall Street as a sign of the health of the global economy. Its shares were 1.9 percent while Merck rose 1 percent.

The Goodyear Tire and Rubber Company rose 14.1 percent, the most of any company in the Standard Poor’s 500 index, after it set a company sales record and reversed its loss from the first quarter of last year.

Shares of the home builder D. R. Horton rose 2.4 percent after it reported a surprisingly strong profit. The company said its fiscal second-quarter profit more than doubled mostly because of a large tax benefit. Its shares were 3.1 percent higher.

Shares of Chevron rose1.7 percent after the company said its net income rose 36 percent, its best quarter since 2008.

In economic news, the government said that consumers spent more in March. But that was because they paid more to buy food or fill up their cars with gas. Their incomes also increased, though, as a result of a cut of 2 percentage points in Social Security taxes

In afternoon trading, the Dow Jones industrial average was up 63.65 points, or 0.5 percent. The broader Standard Poor’s 500-stock index was 3.17 points or 0.23 percent higher. The technology heavy Nasdaq were flat.

Shares of Microsoft, the software maker, dropped 4 percent after it reported that revenues from its Windows operating system fell 4 percent from the same time last year.Despite the soft trading on Friday, all three major indexes are substantially higher for the week. The Dow has gained more than 2 percent, while both the S.P. and the Nasdaq have added about 1.6 percent.

Bond prices are falling, sending yields higher. The yield on the 10-year Treasury note fell to 3.31 percent from 3.32 percent late Thursday.

In Europe, the CAC 40 in Paris was flat, while the DAX in Frankfurt was up 0.4 percent. The FTSE 100 in London was closed as the country celebrated the nuptials of Prince William and Kate Middleton.

Economic reports from Europe were downbeat. Inflation in the 17 euro countries crept up to 2.8 percent in April, official data showed, keeping the pressure on the European Central Bank to raise interest rates again later this year.

That has aroused concerns that higher borrowing costs may make it harder for financially troubled countries like Greece, Ireland and Portugal to return to growth and manage their debt.

Other signs for the euro zone remained mixed. Unemployment was steady at 9.9 percent in March, although Spain’s rate rose sharply to a new euro zone record of 21.3 percent in the first quarter.

Nearly 5 million people are out of work now in Spain, the government said, adding pressure on the country as it tries to recover from nearly two years of recession and convince investors that it can handle its own debt load.

Two of Europe’s leading industrial companies reported hefty growth in first-quarter earnings. The German carmaker Daimler AG said net profit nearly doubled as its luxury Mercedes brand kept up its strong sales performance in China.

Total, Europe’s third largest oil producer, said its profit grew 50 percent in the first quarter thanks to sharply higher oil prices.

Meanwhile in Asia, equity markets also reacted nervously to the weak economic data in the United States. American demand for Asian exports may actually slow, said Dariusz Kowalczuk of Crédit Agricole in Hong Kong.

Hong Kong’s Hang Seng index closed down 0.4 percent to 23,805.63, with renminbi units of Hui Xian Real Estate Investment Trust falling 9.4 percent in their trading debut. They are the first equity securities denominated in China’s currency to trade outside of mainland China.

Japan’s Nikkei 225 was closed for the start of Golden Week holiday.

Article source: http://feeds.nytimes.com/click.phdo?i=f490b4187ea14c7055565eb34eae9274