US Regulators Likely to Scrutinize Vioxx Adverse Events

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NEW YORK, May 01 (Reuters) - Merck & Co.'s arthritis drug Vioxx, taken

by more than 6 million Americans since its 1999 debut, is likely to face

stepped up scrutiny from US 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 [uS]

Food and Drug Administration, and could delay or derail Merck's plans to

market Vioxx for rheumatoid arthritis, " said 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.

The nation's largest US drug maker has said that it plans soon to ask

the FDA to widen the approved use of Vioxx to include rheumatoid

arthritis, the crippling hereditary form of arthritis afflicting 2.1

million Americans.

In late March, Merck said in a statement that preliminary data from a

study of 8,000 rheumatoid arthritis patients showed that those taking

Vioxx suffered from far fewer ulcers and other gastrointestinal side

effects than those who took a popular older arthritis drug, naproxen.

But Merck said that patients using naproxen - a generic painkiller

made by many companies - 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. That study did not include a placebo comparison.

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 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, said 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, " Saks said, referring to the drug's total sales.

FDA spokesperson Cruzan told Reuters that she could not comment on

how closely her agency might scrutinize 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 that 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 3 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 Wednesday, Merck spokeswomen Jan Weiner told Reuters that the lower

rate of 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 that there was no evidence

that Vioxx had actually put patients at higher risk of such adverse

events. Instead, she said that 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.

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 rheumatoid 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.

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