Vioxx gets FDA nod for comebackf1
Panel allows drug to market; Celebrex, Bextra get OK (Full Article)

By Stephanie I. Cohen & Val Brickates
Kennedy, MarketWatch
Last Update: 7:06 PM ET Feb. 18, 2005

WASHINGTON (MarketWatch) - A U.S. Food and Drug Administration advisory panel narrowly agreed Friday that Merck's recalled drug Vioxx was safe enough to return to the market, and gave the regulatory green light to Pfizer's Celebrex and Bextra.

The panel voted 17-15 to allow Vioxx to come back to pharmacy shelves, but only if it bears a stern "black box" warning advising users that it can cause heart trouble in patients at risk of developing cardiac problems.

Likewise, the FDA panel also recommended upholding the market approvals for Pfizer's Celebrex and Bextra. Those pain medications will carry similar "black box" warnings.

Because of the proposed black box warnings, the FDA will discourage both Pfizer (PFE: news, chart, profile) and Merck (MRK: news, chart, profile) from doing any direct consumer advertising for the drugs.

Merck officials told the FDA panel on Thursday that it would consider relaunching the drug if the FDA did not rescind its marketing approval. Merck had pulled Vioxx abruptly from the market on Sept. 30 over concerns that long-term use could lead to heart attack or stroke in some patients.

After the vote, FDA panel members advised caution in prescribing the drugs. Agency officials said decisions on how the black box warnings will be worded will be made within the next few weeks.

While the votes cast Friday are not final regulatory decisions, the FDA generally always follows the recommendations of its advisory panels. Details of the "black box" warnings will be worked out at a later date.

The panel also voted to slap a tentative warning on almost 20 non-steroidal anti-inflammatory drugs, known as NSAIDs, advising users that no definitive studies have been conducted to determine if long-term use can cause cardiovascular problems. The drug group includes such popular over-the-counter medications as ibuprofen and naproxen.

Because many NSAIDs have been on the market for decades and now are sold generically, members of the advisory panel admitted it will be difficult to find companies to conduct long-term studies on the drugs. The FDA may therefore consider running its own studies or request they be sponsored by the National Institutes of Health.

The news sent Merck shares skyward, with the stock closing up 13 percent to $32.61 at the close. Shares of Pfizer (PFE: news, chart, profile) jumped 7 percent to close at $26.80.

A company spokeswoman said Merck would not comment on the vote. Pfizer officials put out a press release late Friday.

"Pfizer is committed to conducting longer-term studies on the cardiovascular profiles of both Celebrex and Bextra," the company said in the release. "As it has throughout recent months, Pfizer will continue to fully support Celebrex and Bextra and to make appropriate long-term investments so that patients may benefit from these important medicines."

The votes conclude three days of hearings by the FDA advisory committee into the overall safety of a group of pain relievers called non-steroidal anti-inflammatory drugs (NSAIDs), several of which are now believed to cause cardiovascular problems in patients who are predisposed towards developing those conditions.

In particular, the committee focused on a subset called Cox-2 inhibitors, which are believed the carry greater risks. Vioxx, Bextra and Celebrex are all Cox-2 inhibitors.

The panel expressed most confidence in re-approving Celebrex, voting 31-1 to keep it on the market.

It was far less confident about Bextra, however, a drug that already carries two other black box warnings. A first vote for Bextra had to be re-cast when too many panel members abstained. The final vote was 17-13 in favor of keeping it on the market, with 2 abstentions.

"The hazard has been clearly shown with rofecoxib [Vioxx]," said panel chairman Alistair Wood. "The hazard has also been clearly shown with valdecoxib [Bextra]."

The panel's decision to allow Vioxx back on the market should bolster Merck's legal position on the drug. Currently, the company currently faces more than 600 lawsuits over Vioxx, ranging from personal injury suits to investigations by the Department of Justice and two Congressional committees.

Critics have accused Merck of knowing as early as 1999 that Vioxx could cause cardiac problems, but elected to keep the drug on the market anyway. Analysts say Merck could face $20 billion in liability over Vioxx.

On Thursday, Merck researchers told FDA officials that it might consider putting the drug back on the market.

Addressing the FDA panel on Thursday, Merck research chief Peter Kim said: "If the advisory committee and the FDA conclude that the benefits of this class outweigh the risks in some patient populations, then we would have to consider the implications of these new data given the unique benefits Vioxx offers."

Merck has maintained it believes Vioxx only causes problems after being taken for at least 18 months or in very high doses. It also asserts the drug is of value to many pain sufferers as it doesn't cause the gastrointestinal bleeding associated with other non-steroidal painkillers.

Stephanie I. Cohen is a reporter for MarketWatch based in Washington.
Val Brickates Kennedy is a reporter for MarketWatch in Boston.

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 Daily Supplement May Boost Birthweight of Babies In The Developing Worldf2
2005-03-03 - The Lancet

Giving pregnant women in the developing world a daily supplement containing 10 vitamins and five minerals could help increase the birthweight of their babies, concludes a study published online by The Lancet.

A third of global deaths happen in children younger than 5 years; most occur in the neonatal period - the first four weeks of life. Low birthweight (less than 2500 g) underlies many of these deaths. Around 25 million low-birthweight infants are born every year. Maternal nutritional status is closely linked with foetal weight. Increases in macronutrient consumption during pregnancy can lead to increased birthweight.

David Osrin (Institute of Child Health, UK) and colleagues did a trial to test whether multiple micronutrient supplementation at one recommended daily allowance would increase birthweight and help prolong pregnancy to full term. 1200 women from Nepal, who had reached up to 20 weeks of pregnancy, were recruited onto the trial between August 2002 and October 2003. Women were randomly assigned to receive either a supplement containing 10 vitamins (vitamin A, E, D, B1, B2, B6, B12, C, niacin, folic acid) and five minerals (iron, zinc, copper, selenium, iodine) or the nationally advised tablets containing iron and folic acid once daily for an average of 160 days. Birthweight data for 1052 babies was available in the analysis. The average birthweight was 2733 g in the control group and 2810 g in the intervention group, representing an average difference of 77 g and reduction in the prevalence of low birthweight by 25%. The length of pregnancy was 1·5 days longer in the intervention group than in the control group but that result was not significant. The difference in the mean birthweight was more marked in female infants (108 g compared with 44 g in males) and in infants of mothers whose body mass index was 18·5kg/m2 or more (83 g compared with 54g in those with a body mass index of less than 18.5 kg/m2).

Dr Osrin concludes: "Our tentative finding of a differential effect of the supplement is interesting. The effect of multiple micronutrients on foetal weight seems to have been enhanced in female infants, in births of higher order, and in babies of women with greater body-mass index. The public-health implications of our findings await confirmation by the results of other studies currently underway."

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 NIH Bans Outside Payments For Scientistsf3
Agency Hopes To End Controversy Over Consulting Deals (Full Article)

The Associated Press
Updated: 6:15 p.m. ET Feb. 1, 2005

WASHINGTON - The National Institutes of Health banned its scientists from working as consultants for pharmaceutical, biotechnology and similar businesses, a step officials hope will end controversy over paid consulting arrangements by some of its doctors.

"Nothing is more important for NIH than preserving the public's trust," NIH Director Dr. Elias A. Zerhouni said Tuesday.

The new rules also will prohibit scientists from holding stock in such companies and will restrict the amount of stock that other NIH employees can own in pharmaceutical and biotechnology companies.

The ban on outside work by NIH scientists covers research institutions, including those that receive grants from the NIH, health care providers, insurers and related trade associations.

The scientists will be allowed, however, to teach courses and give lectures related to their work, as well as write articles and textbooks.

"Clearly we do not want to impair scientific interchange," Zerhouni said at a briefing.

Zerhouni also said that the institute last month established rules requiring researchers who receive royalties from experimental treatments they helped develop to disclose those royalties to patients.

'A clear necessity'

Such disclosure "is a clear necessity," said Zerhouni. Cases of NIH scientists failing to disclose such royalties were first reported by The Associated Press. The new ethics rules will take effect when they are published, probably within a day or two. They will also include a $200 limit on awards that institute researchers can accept, with a few exceptions, such as the Nobel Prize.

Zerhouni said the institutes also will begin evaluating any potential conflicts of interest with members of its outside advisory panels.

He described early reaction to the new rules from NIH staff as "mixed." Rep. Joe Barton, R-Texas, chairman of the House Energy and Commerce Committee, praised Zerhouni for "taking a step that is both difficult and necessary."

The new rules also drew praise from Rep. Diana DeGette, D-Colo., who has been critical of Institute policies allowing its scientists to take consulting jobs.

"NIH's previous ethics requirements were unworkable - not at all what the public deserves from our nation's premier research institution," said DeGette. Sen. Tom Harkin, D-Iowa, also welcomed the decision, saying the new rules "should help restore the public's trust that federal biomedical research dollars will be spent wisely and prudently."

Private consulting deals

In September, the Institute proposed to ban outside consulting work by its roughly 5,000 or so scientists in the wake of media reports that some researchers received thousands of dollars from industry. That proposal was intended to give the agency time to develop new ethics regulations.

It doesn't affect scientists' official duties in turning basic research into health treatments, duties that often involve some work with industry.

Rather, the restrictions focused on a fraction of agency scientists - about 120 by one count - who have arranged private consulting deals with industry. In one case uncovered by Congress, Pfizer Inc. allegedly paid an NIH researcher half a million dollars over five years, in part to help the company's research of brain disease.

Such arrangements have raised widespread concern in Congress and among the public as to whether they represent a conflict of interest for researchers. In May, Zerhouni told Congress that the agency needed to tighten its rules but said some collaboration with industry and academia is vital to advance science and to translate discoveries into medical practice.

"It would be a mistake to ban all compensated activities with outside organizations. Such an action would be bad for science, unfair to the employees and ultimately hinder our efforts to improve the nation's health," he said.

And former NIH Director Harold Varmus said that allowing NIH scientists to do outside consulting has helped in recruiting better researchers.

Varmus, now president of the Sloan-Kettering Cancer Center, relaxed some rules, allowing NIH scientists to do outside consulting and accept speaking fees, when he headed the agency in the 1990s.