NEW YORK, May 25 (Reuters) - Merck & Co. Inc. said on Wednesday that
rheumatoid arthritis patients taking its drug Vioxx suffered less than half the
incidence of ulcers and serious gastrointestinal problems of those taking a
popular older drug, naproxen, in a large safety trial.
Data from the 8,000-patient study, called VIGOUR, were presented in San
Diego at Digestive Disease Week, the nation's largest meeting of
gastrointestinal (GI) specialists.
"Results on gastrointestinal safety of Vioxx were very impressive," said
PaineWebber drug analyst Jeffrey Chaffkin, who noted that Vioxx was developed to
offer equivalent effectiveness of older arthritis drugs but with milder GI side
effects.
Merck said its blockbuster Vioxx was well-tolerated in the study, although
patients taking it had more heart attacks than those taking naproxen during the
13-month worldwide trial.
Merck attributed naproxen's better results in heart attacks to the older
drug's presumed ability to prevent blood platelets from clumping together to
form blood clots. It said no difference in heart attack incidents was seen in
earlier trials that compared Vioxx to other standard arthritis drugs.
Moreover, Merck said there was no significant difference in heart attacks
between the Vioxx and naproxen groups in VIGOUR, when excluding consideration of
the 4 percent of the total study group that had previously suffered heart
attacks, strokes, other cardiovascular incidents or had angioplasty or more
serious medical interventions.
US regulators approved Vioxx for acute pain and osteoarthritis last year on
the basis of studies comparing it to placebos. Osteoarthritis is the most common
form of arthritis and causes breakdown of the affected joints.
After launching the drug, Merck conducted the VIGOUR trial among rheumatoid
arthritis patients to see whether Vioxx was indeed safer than traditional
arthritis drugs.
Rheumatoid arthritis is the less common form of arthritis, in which the
body's immune system attacks the joints. Vioxx is not currently approved for
treating rheumatoid arthritis, but Merck has completed Phase III trials of the
drug for the autoimmune disorder and plans by the end of the year to seek US
marketing approval to treat the condition.
VIGOUR pitted Vioxx against naproxen, one of the most commonly used members
of the family of traditional nonsteroidal anti-inflammatory drugs (NSAIDs),
which also includes aspirin.
Patients were divided into two groups, one of which took a daily 50
milligram dose of Vioxx, two to four times higher than the standard
osteoarthritis dose of Vioxx. Others took naproxen in a 500 milligram dose twice
a day, which is its standard daily regimen for treating rheumatoid arthritis.
Vioxx reduced the risk by 54 percent of symptomatic ulcers and complicated
GI events, including ulcers, perforations, obstructions and bleeding in the
upper GI tract, compared to the naproxen group, Merck said. The difference in
side effects was statistically significant. "The rate of these events was 4.5
percent per year among patients taking naproxen, compared to 2.1 percent per
year among patients taking Vioxx," Merck said in a prepared release.
When considering only complicated GI events, but not symptomatic ulcers,
Vioxx reduced the risk by 57 percent, compared to naproxen, a difference which
was also statistically relevant.
"The rate of these events was 1.4 percent per year among patients taking
naproxen, compared to 0.6 percent per year among patients taking Vioxx," Merck
said. "In this study, Vioxx also reduced bleeding from the GI tract by 62
percent" compared to naproxen, Merck said.
There was no difference in cardiovascular mortality and incidence of strokes
in the two VIGOUR groups, Merck said. But it added that "significantly fewer
heart attacks were seen in patients taking naproxen (0.1 percent) compared to
the group taking Vioxx (0.4 percent) in this study."
"The reduction in heart attacks is consistent with naproxen's ability to
block platelet aggregation," Merck said. It said naproxen's ability to prevent
platelet-clumping was similar to that of low-dose aspirin, which is taken by
many patients with cardiovascular problems to prevent heart attack and stroke.
No patients taking aspirin were admitted in the VIGOUR trial. But Merck said
the 4 percent of the total study group who had previous cardiovascular incidents
and medical procedures would have been appropriate candidates for taking
cardio-protective doses of low-dose aspirin.
Among the remaining 96 percent of patients, Merck said there was no
significant difference in heart attack rates between the Vioxx and naproxen
groups--0.1 percent for those on naproxen and 0.2 percent for patients on Vioxx.
"When you exclude consideration of the 4 percent who have had previous
cardiovascular incidents, the difference in heart attacks between the Vioxx and
naproxen patients are less a problem than previously speculated. I don't think
it's an issue at all," said Tony Butler, a Lehman Brothers analyst.
About 46 percent of the total VIGOUR group had what Nerck termed a previous
history of cardiovascular disease, which included people with hypertension.
Some other analysts, including Brown Brothers Harriman's Mike Krensavage,
said the heart-attack difference remained very much an issue, particularly given
the demographics of the population taking Vioxx.
"The average age of patients in the study was 58, and 46 percent had some
history of cardiovascular disease, so the targeted population is vulnerable to
cardiovascular problems. Heart attacks are serious events. There's no way to
say, 'This is nothing.' These data should encourage regulators to take a closer
look at this drug," Krensavage said.
Although the trial was meant to test for safety, Merck said both Vioxx and
naproxen reduced the severity of rheumatoid arthritis equally in the VIGOUR
trial.
Merck has said it plans to submit the VIGOUR data to US regulators within
the next few months, in hopes the GI safety data can be added to the Vioxx
insert label.
Vioxx is designed to provide similar relief for arthritis and pain as
traditional NSAIDs, but with less risk of causing ulcers and gastrointestinal
damage.
It and Pharmacia Corp.'s drug Celebrex selectively block the Cox-2 enzyme
linked to inflammation. Older arthritis drugs like naproxen also block the
enzyme, but are believed to cause more ulcers and GI problems by also blocking
the related Cox-1 enzyme that protects the stomach lining.
