Increased heart attacks, 4X when using Cox-2's came out 4 or 5 months ago. Is there something new????
Here is the old story:
800lawinfo.com
Merck's Vioxx seen facing FDA scrutiny on heart attacks
NEW YORK, April 27 - Merck & Co.'s arthritis drug Vioxx, taken by more than six million Americans since its 1999 debut, is likely to face stepped-up scrutiny from U.S. regulators because of the number of patients who suffered strokes and heart attacks after taking the medicine in new clinical trials, analysts said.
``The heart attacks and strokes could be a serious concern for the Food and Drug Administration, and could delay or derail Merck's plans to market Vioxx for rheumatoid arthritis,'' said David Saks, manager of Gruntal & Co's Medical Sciences Fund.
The FDA in recent months has shown far more concern over safety of drugs already on the market and those awaiting approval, following the recall of several medicines linked to deaths and serious side effects.
Vioxx is one of the fastest-selling new drugs in the world. It was approved last May by the FDA for the treatment of acute pain and osteoarthritis -- the most common form of arthritis, caused by normal wear and tear of joints and afflicting 21 million Americans. Some analysts expect sales of Vioxx, which were worth $472 million last year, to swell to $2 billion or more by 2002.
MERCK SEEKS WIDER MARKET
The No. 1 U.S. drugmaker has said it plans to soon ask the FDA to widen the approved use of Vioxx to rheumatoid arthritis, the crippling hereditary form of arthritis afflicting 2.1 million Americans, in which the body's own immune system attacks joints.
In late March, Merck said in a statement that preliminary data from a study of 8,000 rheumatoid arthritis patients showed those taking Vioxx suffered far fewer ulcers and other gastrointestinal side effects than those who took a popular older arthritis drug called naproxen.
But Merck said patients using naproxen -- a generic painkiller made by many companies which is in the same family as aspirin -- had significantly fewer heart attacks and strokes than the Vioxx group. Merck has attributed that negative finding for Vioxx to naproxen's ability to prevent platelets from sticking together. Such platelet clumping can cause blood clots. That study did not include a placebo comparison.
NEW RISK ELEMENT
Some analysts, though, are less than convinced by Merck's explanation.
``This whole situation about heart attacks and strokes adds an element of risk to Vioxx that most people are not looking at. It's not on most people's radar screens, but it should be,'' said Mario Corso, a Boston-based drug analyst for Dutch bank ABN-Amro.
Gruntal's Saks -- who had previously forecast Vioxx could achieve annual sales of $2 billion by 2002, including between $200 million and $300 million for rheumatoid arthritis if it wins that approval -- says FDA scrutiny could threaten those sales prospects.
``The rheumatoid arthritis indication would be icing on the cake. The larger question is how this issue (of heart attacks and strokes) might affect the whole cake,'' he said, referring to the drug's total sales.
FDA spokesperson Susan Cruzan told Reuters she could not comment on how closely her agency might scrutinise Merck's rheumatoid arthritis marketing application and the related heart attack and stroke data.
``It's too early to comment about that. We will review the study and the results for both drugs,'' Cruzan said, referring to comparisons between Vioxx and naproxen.
Meanwhile, Cruzan said the FDA continues to believe that Vioxx is ``effective and adequately safe'' for its labeled uses.
The FDA has overseen a spate of drug recalls in the past three years, nudging companies to voluntarily withdraw their medicines after side effects rarely seen in clinical trials became apparent once the drugs hit the market and were taken by millions of people.
On March 23, Johnson & Johnson said it would severely limit sales of its blockbuster heartburn medicine Propulsid following reports of heart rhythm abnormalities and 80 deaths among users. Only days earlier, Warner-Lambert Co. withdrew its Rezulin diabetes drug, which the FDA said had been linked to 63 deaths from liver failure.
The FDA drew criticism from many quarters, including the CBS television programme ``60 Minutes,'' for allowing Rezulin to remain on the market despite mounting liver abnormalities and deaths among users. The agency has also been accused of ignoring serious side effects linked to two American Home Products Corp. diet drugs used in the once-popular ``fen-phen'' slimming cocktail.
AHP's drugs -- Pondimin (fenfluramine) and Redux (dexfenfluramine) -- were recalled in 1997 after being linked to heart valve problems in some of the six million Americans who had taken the diet suppressants.
CLEAR TREND
On Wednesday, Merck spokeswomen Jan Weiner told Reuters the fewer heart attacks and strokes in the naproxen group, compared to Vioxx, was a ``statistically significant'' finding -- a scientific term meaning it was a clear trend.
But Weiner said there was no evidence Vioxx had actually put patients at higher risk of such adverse events. Instead, she said it was likely that naproxen had conferred protection to patients taking that drug.
``Naproxen blocks platelet aggregation, it keeps them from clumping together. That's in the literature,'' Weiner said, referring to previous medical studies.
As a testament to Vioxx, Weiner said the drug did not show any such higher incidence of heart attacks and stroke in separate studies of osteoarthritis patients and acute pain studies that pitted it against other popular painkillers such as ibuprofen and diclofenac.
Swiss drugmaker Roche Holding Ltd is among the largest sellers of naproxen. Its product is sold under the brand name Naprosyn.
``To our knowledge, naproxen does not prevent heart attack or stroke,'' Shelley Rosenstock, a U.S. spokesperson for Roche told Reuters.
ABN Amro's Corso said he was not reassured by Merck's suggestion that naproxen conferred protection against heart attacks and strokes.
``Medical authorities I've spoken to don't see any special reduction of such cardiovascular events in people taking naproxen,'' Corso said.
``This could conceivably delay approval of Vioxx for rhematoid arthritis. The FDA could ask for another trial to see if the results were a fluke or to add more validity to the findings,'' he said.
Vioxx is a member of a new family of drugs that selectively block the so-called Cox-2 enzyme linked to pain and inflammation. Its 1999 global sales of $472 million, included U.S. revenues of $420 million. Wall Street expects worldwide annual sales of $2 billion by 2002.
Vioxx is locked in a fierce battle with Celebrex, a Cox-2 inhibitor sold by New Jersey drugmaker Pharmacia Corp. that had 1999 sales of $1.5 billion. Both Cox-2 drugs are rapidly stealing market share from naproxen, aspirin and other painkillers called nonsteroidal anti-inflammatory drugs (NSAIDs).
The NSAIDs inhibit Cox-2, but also block the Cox-1 enzyme which protects the stomach lining -- and thus cause over 16,000 deaths in the United States from ulcers and related problems each year. Vioxx and Celebrex, because they ignore Cox-1, are considered much milder on the stomach.
Dr. Steven Geis, a senior researcher for Pharmacia's G.D. Searle pharmaceuticals unit, said Celebrex showed no such higher incidence of heart attacks and strokes when it was also tested against naproxen.
Geis said about 8,000 patients who had osteoarthritis and rheumatoid arthritis participated in the Searle trials, with half taking Celebrex and half taking naproxen.
``We found no differences in the incidence of heart attacks and strokes in patients taking Celebrex and naproxen,'' Geis said. Moreover, Geis said there was no evidence that any NSAID, with the exception of aspirin, prevents heart attacks or stroke.
4/27/2000 |
