Bad news for Aleve. Good news for Celebrex.
In the cold, calculating world of Wall Street, that's how the unfolding drama of new test results on old drugs is playing out, as analysts see bright spots for
amid other drugs' woes.
"The Celebrex outlook may be better than many fear," said UBS analyst Carl Seiden in a research note to clients Tuesday, after Pfizer's drug showed no extra heart risk in a test against Aleve and a placebo. This test, conducted by the National Institutes of Health, examined whether the drugs could reduce the risk of elderly people contracting Alzheimer's disease.
The test showed that patients taking naproxen had a higher risk of cardiovascular and stroke problems.
"Zero signal was seen on Celebrex," said Seiden, who is keeping his buy rating on Pfizer. (He doesn't own shares; his firm has an investment banking relationship.)
The best-known version of naproxen is sold over the counter by
under the brand name Aleve, but other companies make generic versions and it is also available in prescription strength.
The cardiovascular risk was 50% greater for people taking Aleve vs. people taking a placebo, with "most adverse events occurring after 18 months' treatment," said John T. Boris, of Harris Nesbitt, in a Tuesday report to clients with the headline "Celebrex gets unexpected boost from over-the-counter Aleve."
Boris reaffirmed his outperform rating on Pfizer. "We believe this study increases the probability that Celebrex will remain on the market," he said.
Boris added that the stock "currently reflects expectations" that Celebrex and a similar drug, Bextra, will be pulled from the market. (His firm doesn't have an investment banking relationship; his research report says he, an associate, or a member of either household owns shares.)
On Friday, Pfizer's stock was pummeled after a clinical trial sponsored by the National Cancer Institute showed that Celebrex patients had a higher risk of heart and stroke problems compared with patients receiving a placebo. Although Celebrex is prescribed mostly for arthritis and pain, the test halted on Friday looked at whether the drug can prevent certain colon tumors.
The announcement caused concern among doctors and patients about alternative products and terrified investors that Celebrex could go the way of Vioxx, which
pulled from the market on Sept. 30.
Merck acted after research showed patients taking Vioxx for more than 18 months had a higher risk of cardiovascular injury than patients receiving a placebo. Vioxx is a COX-2 inhibitor, as are Celebrex and Bextra.
Pfizer is keeping both drugs on the market, but has suspended direct-to-consumer advertising for Celebrex until the Food and Drug Administration reviews recent tests that have produced conflicting results.
Celebrex's recommended dose is 100 milligrams to 200 milligrams for osteoarthritis, a degenerative joint disease, and 200 milligrams to 400 milligrams for rheumatoid arthritis, an inflammatory disease.
But look what happened in the last few days:
There was no cardiovascular risk in the Alzheimer's disease test, in which patients received 400 milligrams of Celebrex.
There was no cardiovascular risk in a Pfizer-sponsored colon tumor test, whose patients received 400 milligrams of Celebrex.
But there was a cardiovascular risk in the National Cancer Institute colon tumor test, whose Celebrex patients received 400 milligrams to 800 milligrams.
Analysts have pointed out that if Celebrex and/or Bextra were pulled from the market, patients would have to seek pain relief in older drugs collectively known as nonsteroidal anti-inflammatory drugs, or NSAIDs. The group includes naproxen as well as ibuprofen and aspirin.
Analysts also have noted that NSAIDs haven't been subject to the long-term clinical trials that have raised cardiovascular risk questions about the COX-2 drugs. Now, the Alzheimer's disease study "accentuates the unknown risk for older NSAID medications that have not been extensively studied on a long-term basis," said Harris Nesbitt's Boris.
UBS' Seiden said the dose of over-the-counter naproxen linked to greater cardiovascular risk is equal to or lower than the maximum allowable doses on the drug's label. He added that the dose in the Alzheimer's disease test is only one-third the recommended dose of prescription-strength naproxen for treating osteoarthritis.
Having compared test results, Seiden concluded that patients switched from Celebrex to naproxen "could actually be potentially placed at a higher risk of experiencing a cardiovascular event, exactly the opposite reason why they were likely switched in the first place."
One More Slice of Irony
The naproxen-Celebrex test also dragged Merck back into the pain-drug debate. "We think these findings are a relative negative for Merck," said Chris Shibutani, of J.P. Morgan, in a report to clients on Tuesday. "It works against their argument that naproxen has a 'beneficial' heart protective effect, which made Vioxx look relatively worse in the VIGOR trial than it would against placebo."
VIGOR is the clinical study cited by critics as the signal to Merck that Vioxx should have been removed from the market. VIGOR compared Vioxx to naproxen to determine which drug caused fewer gastrointestinal side effects, a significant problem for patients taking arthritis drugs and pain relievers.
Preliminary VIGOR results became available in March 2000, showing "a difference in the cardiovascular event rate" between Vioxx patients and naproxen patients. The results conflicted with results of tests that Merck had submitted to the FDA comparing Vioxx vs. placebo and comparing Vioxx vs. non-naproxen pain relievers.
Merck said it couldn't make a decision on Vioxx's possible heart risk based on VIGOR because the study didn't include a placebo as a comparison. Because naproxen has anticlotting characteristics similar to aspirin, Merck concluded that "the most plausible explanation" was that naproxen might have a heart benefit.
Merck's study was later published by
The New England Journal of Medicine
. The Vioxx label was changed by the FDA in 2002, incorporating results from the VIGOR study.
"We believe ... that the 'naproxen benefit' claim has always been viewed with skepticism by the medical community and Wall Street due to a lack of supporting data," Shibutani said.