Tuesday, 22 May 2012

FDA staff sends mixed message on J&J drug Xarelto

WASHINGTON (Reuters) - U.S. drug reviewers had mixed opinions about whether Johnson & Johnson's blood thinner Xarelto reduced the risk of new heart attacks and strokes in people with heart problems, setting the stage for heated debate by outside experts later this week.

Some U.S. Food and Drug Administration staff raised doubts about how well the drug worked, given the high number of people who dropped out of studies on the pill. But the FDA's clinical reviewer recommended approval.

But the staff appeared united in the view that the data did not prove Xarelto reduced the risk of death in patients with acute coronary syndrome, which analysts had seen as the drug's most important advantage for treating this heart condition.

An FDA advisory panel of outside experts will vote Wednesday on whether to recommend the drug. The FDA usually follows panel recommendations, although it is not required to. The agency is due to make a final decision on Xarelto by the end of June.

The FDA's medical team leader, Dr. Thomas Marciniak, questioned whether Xarelto truly helped people with heart problems, since J&J lost track of an average of 12 percent of people taking the pill in clinical trials.

He also said the company did not count three people who died after taking the drug, which could skew results.

"These three uncounted deaths may be the tip of the iceberg regarding problems with missing data," he said in FDA briefing documents posted online on Monday.

But the FDA's clinical reviewer, Dr. Karen Hicks, said J&J recognized the problem of missing data and tried to fix it, and many other heart trials have the same problem.

"I recommend approval of Xarelto to reduce the risk of cardiovascular events in patients with acute coronary syndrome," she said in the documents.

However, Hicks said Xarelto does not reduce the risk of death, and also said minor bleeding issues with the pill may be a concern if the drug is approved.

Xarelto, which J&J developed in partnership with German drugmaker Bayer AG, is already approved to reduce the risk of blood clots in the legs and lungs of people who have had knee or hip replacement surgery. It is also approved to prevent strokes among people with irregular heartbeats, called atrial fibrillation.

The companies are hoping to get Xarelto approved for a third use: reducing the risk of stroke and heart attack in people with acute coronary syndrome (ACS).

ACS is an umbrella term that refers to people who have heart attacks or chest pain usually caused by a blocked coronary artery. About a million people in the United States are hospitalized each year after having an ACS episode, usually a heart attack, according to researchers.

Larry Biegelsen, analyst at Wells Fargo, said he still believes the FDA advisory panel will recommend Xarelto for ACS patients because of the FDA reviewer's recommendation.

"We expect a very heated debate on (Wednesday), however, we continue to expect a positive outcome," he said in a research note.

He said the increased risk of bleeding meant Xarelto would have modest sales for people with acute coronary syndrome, reaching $342 million in 2016. The drug's use in such patients will be about 22 percent of overall Xarelto sales of $1.6 billion in 2016, he said.

Xarelto is one of three new medicines that offer potential advantages over older drugs to prevent strokes and other dangerous conditions caused by blood clots, in a market worth up to $10 billion in annual sales, according to Wall Street forecasts.

Investors have tried to bet on which of the three will become the dominant player in a race between Xarelto, Eliquis from Pfizer Inc and Bristol-Myers Squibb Co, and Boehringer Ingelheim's Pradaxa.

Xarelto's rivals failed in treating patients with ACS, giving Bayer and J&J a potentially distinct market - although stroke prevention in atrial fibrillation is seen as the most lucrative use for the new drugs.

Shares of J&J rose 0.3 percent to $63.55 in morning trading on the New York Stock Exchange, in line with the broader Arca Pharmaceuticals Index. Bayer shares were 2.6 percent higher on the Frankfurt Stock Exchange.

(Reporting by Anna Yukhananov; Editing by Gerald E. McCormick and John Wallace)

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