Health Biz: A black box warning for COX-2?

WASHINGTON, Jan. 18 (UPI) -- A black-box warning from the Food and Drug Administration about the cardiovascular risks of COX-2 inhibitor drugs -- researchers are calling for it, analysts are predicting it -- could be the best short-term solution for the pharmaceutical industry.

The evidence points to a significantly higher risk of cardiovascular events for patients taking COX-2 medications, such as Celebrex and Bextra from Pfizer and Vioxx from Merck.

"A black-box warning that alerts practitioners to the potential cardiovascular hazards, especially in patients at moderate to high risk, seems timely for all COX-2 inhibitors," Dr. Bruce Psaty of the University of Washington in Seattle wrote in Tuesday's edition of the journal Circulation.

That would leave it to patients and their physicians to weigh whether the benefits of using a COX-2 -- relief of pain and inflammation -- outweigh the risks.

It is not cut and dried, of course, because, studies have shown, the biggest increase in risk from these technology blockbusters comes when patients take them at dosages much higher than the usual amount recommended for patients with arthritis or chronic pain.

"If there is a black box, we believe here at Datamonitor there is a dose-related effect," Duncan Emerton, a senior healthcare analyst the market analysis company, told UPI's Health Biz. "If used with increased labeling, we believe these drugs to be safe."

The decision patients and physicians will make together will go something like: What risk does the usual dosage of 100 milligrams per day of Celebrex bring if a 400-milligram to 800-milligram dose per day causes a significant increase in the likelihood of cardiovascular events, as studies have shown?

Until new studies are designed and completed, that becomes the $64,000 question or, for pharmaceutical companies, perhaps the billion-dollar question.

Dr. Curt D. Furberg, a professor of public health sciences at Wake Forest University, wrote in Circulation that physicians should stop prescribing Bextra or use it only in dire cases.

"In the absence of evidence of safety, it is prudent to avoid the use of Bextra altogether or use it only as a drug of last resort," he wrote. "It is currently unclear to what degree the risk extends to patients treated with lower doses for arthritis because studies of sufficient size and duration have not been reported."

The FDA and the European Medicine's Agency have scheduled meetings in the coming weeks on the COX-2 issue, but it is unlikely a decision to withdraw the entire class of drugs from the market is forthcoming.

While this process is ongoing, the COX-2 drugmakers occupy a difficult position. Merck's Vioxx is out of the game for now and Pfizer has kept Celebrex and Bextra on the market, but has pulled all advertising on them -- even before the FDA told the company to do so.

Emerton said if regulatory agencies decide to keep the class active it would be good news for companies that make or are developing COX-2 inhibitors -- Pfizer, Novartis, Merck and GlaxoSmithKline -- but still, sales will be adversely affected because doubts about the drugs linger.

Drugmakers could take the opportunity to try to reassure patients and physicians they are serious about the long-term safety studies. In any case, the controversy likely will change how pharmaceutical companies advertise their products.

Tom Rosenwald, a partner and leader of the Healthcare Product Practice at Ray & Berndtson, an executive search firm in New York City, said pharmaceutical advertising has "just gotten out of whack."

"There's tons of money being thrown at this, and I'm not sure that anybody has a realistic understanding of the return on investment," he told Health Biz.

The COX-2 drugs, he said, appeal to a broad category of consumers and the more they are induced by ads to take drugs that have risks and dangers, the more liability they assume.

Rosenwald said the more a drug contains the potential danger of side effects, the less direct-to-consumer advertising there should be and he suggested FDA might consider that approach.

KID GLOVES FOR LEAVITT DURING HEARING

Doing more with available Medicaid dollars, the Food and Drug Administration drug approval process and the States Children's Health Insurance Program all came up Tuesday at the Senate Health, Education, Labor and Pensions committee's hearing on Michael Leavitt's nomination to be be Secretary of Health and Human Services.

Committee members got no solid answers, but they still treated the current Environmental Protection Agency chief with kid gloves pending a more important hearing scheduled for Wednesday before the Senate Finance committee.

One of the more interesting remarks from the former governor of Utah came at the expense of current HHS Secretary Tommy Thompson, a former governor of Wisconsin.

Leavitt, known to toe the administration line much more closely than the outspoken Thompson, said in one breath he would "build on the legacy he (Thompson) has built." That was closely followed by Leavitt's statement that an important mission for HHS is to assure Americans "their food is protected and safe."

This was a jab at Thompson's comment during his resignation speech in December: "For the life of me, I cannot understand why the terrorists have not attacked our food supply because it is so easy to do."

Sen. Edward Kennedy, D-Mass., fired off some questions on expected Bush administration Medicaid cuts without really expecting answers, although Leavitt has some experience as governor dealing with balancing a state budget and paying for Medicaid expenditures, as well as trying to wrestle waiver approvals from HHS for state plans to change the program to serve different indigent populations.

"We hear the administration is planning to cut the federal support for Medicaid," Kennedy said, noting that 38 states already had limited Medicaid eligibility and 34 have cut benefits trying to reduce program spending in times of tight state budgets.

"I have been one of those states," Leavitt said, but added his philosophy of Medicaid is that "we can expand the number of people that we serve with available resources."

To which Kennedy responded: "But if you come to the point where you are going to have a reduction in services ... if you can't stretch it out ... I imagine you are going to have a concern about that."

Kennedy also tossed SCHIP on the table, referring to the $1 billion in SCHIP funds that went unused by states last year and were returned to the federal government general fund. He said there has been bipartisan efforts in the past to return that money to SCHIP states -- but so far the administration hasn't indicated it is willing to restore the program funds.

Leavitt said he was "very optimistic" about it, but had no other comment on the controversy.

When asked how Congress could help FDA ensure it has the authority and resources to do its drug approval job in a timely manner, Leavitt responded he is aware of the "constant tension" between the need to bring a drug quickly to market while ensuring safety. He said FDA needs to find the balance between the two that expedites innovation while protecting the American public.

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E-mail: ebeck@upi.com