FDA official: Merck had time to put out warning about Vioxx

Monday, February 13th 2006, 10:35 am

By: News On 6

NEW ORLEANS (AP) _ Merck & Co. could have put out a warning that its popular painkiller Vioxx might increase the risk of heart attacks as soon as the first evidence showed up, rather than waiting for federal approval, a former Food and Drug Administration official testified Friday.

Richard Kapit said there was plenty of time to have done that before Richard ``Dickie'' Irvin began taking Vioxx, which his widow claims caused his fatal heart attack in May 2001, after a month on the drug.

Merck says it gave information about the risk to the FDA in 2000, but the agency didn't approve the label change until April 2002. The information in question, from a study known as VIGOR, was that heart attacks occurred five times as often in patients taking Vioxx as those on another drug, called naproxen.

Kapit said a regulation called ``Changes Being Effected'' or ``CBE'' lets a company change a drug label as soon as it applies for permission to add or strengthen a warning, precaution, or other information about a serious side effect.

``The FDA is a bureaucracy ... you don't want to wait until it goes through all the records,'' he said a bit later.

He said he saw hundreds of such applications during his years at the FDA, which he left in 2002.

But instead of applying for a CBE to add the caution and making a separate application to delete a warning about gastrointestinal side effects, Merck used the same application for both, Kapit said. Deleting a warning does need FDA approval beforehand, he said.

``We had made all the data available to the FDA, the medical community and the general public in all sorts of ways,'' Merck spokesman Kent Jarrell said outside the courtroom. ``So we felt the most proper and most responsible thing to do was work that process with the FDA and the medical community.''

Kapit worked for the FDA for 16 years, 11 of them spent as a drug application reviewer analyzing adverse effects. He did not work on Merck's application for Vioxx. Under cross-examination, he said he based his analysis on about 80 pages of documents supplied by Irvin's widow, Evelyn Irvin Plunkett, and his knowledge of FDA regulations.

Merck scientists knew about the fivefold danger in July 5, 2000, according to an internal memo shown to Kapit.

But a study paid for by Merck and published in November 2000 by the New England Journal of Medicine said the difference was fourfold, and the probable reason was that naproxen protects the heart.

The journal's executive editor, Dr. Gregory Curfman, testified in a videotaped deposition played for the jury Friday that the information was definitely relevant, of interest to his readers, and should have been added to the study before publication.

The study had been submitted in May 2000. Merck contends that the difference was caused by heart attacks which occurred after a reporting deadline set in the study; Curfman said scientific journals expect important updates.

Curfman's testimony ended the first week of the federal trial _ the retrial of a case which originally ended with a hung jury in Houston, where it had been moved because of Hurricane Katrina.

As those deliberations began, the New England Journal of Medicine published an editorial criticizing the study for omitting negative data and for suggesting only that naproxen might have protected the heart, without saying Vioxx could have increased the likelihood of heart attacks.

Merck pulled the drug from the market in September 2004, after another study showed that it could double the risk of heart attacks. The company contends its use is safe for up to 18 months, and that once it realized there was increased danger, it immediately withdrew the drug.

The article published five months later in the Journal did include the 18-month figure, but it twice was preceded by a scientific term that Curfman insisted be inserted to signal that it was a hypothesis _ not a proven fact.

More of Curfman's deposition will be played when the trial resumes Monday. Testimony is expected to last most of the week, with closing arguments expected Friday.