Signs of Depression

By Lisa Richwine

WASHINGTON (Reuters) - U.S. regulators said on Friday they would review a study showing a Merck and Schering-Plough cholesterol drug worked no better than a generic in preventing the build-up of arterial plaque.

The Food and Drug Administration said it was not advising doctors to stop prescribing Vytorin, but the agency's announcement unnerved investors and sent shares of the two companies lower.

The FDA said it could take up to six months to review final results of the study, called Enhance, and decide if any regulatory action was needed. A final report from the companies could be available within a couple months, FDA officials said.

In the meantime, patients with questions about the Enhance study should talk with their doctors, the FDA advised.

"At this time, it is not clear why the lower levels of LDL cholesterol in the patients who took Vytorin did not lead to lesser amounts of plaque compared to patients treated with simvastatin alone," an FDA statement said.

Simvastatin is the generic name for Zocor. Vytorin combines Zocor with a newer cholesterol-fighting pill called Zetia. LDL is the "bad" cholesterol.

The agency's review put an even bigger spotlight on a debate over Vytorin's value in the wake of the Enhance results early last week and concern over a long delay in releasing the data.

Major medical groups, prominent cardiologists and U.S. lawmakers have weighed in, while prescriptions for the drug have slipped.

Merck & Co Inc's shares closed down 3.6 percent at $47.79 on the New York Stock Exchange. They had earlier fallen as much as 14 percent.

Shares of Schering-Plough Corp, which had dropped as much as 13 percent, closed down 5.7 percent at $19.02, also on the NYSE. The two stocks have fallen more than 20 percent since the results of the study were released.

NO IMMEDIATE ACTION

FDA officials said they may consider possible changes to the Vytorin label but felt no action was needed immediately.

"The FDA is attempting to buy time so noise can be filtered out and cooler heads can look at the Vytorin data, but it is unlikely even the FDA will be able to draw clear conclusions," said Viren Mehta, principal at Mehta Partners.

"For a clear picture, we will need to wait for outcomes data (data on heart attack and stroke risk) from larger Vytorin trials" due by 2010 or 2011, Mehta said.

Merck and Schering-Plough sell Vytorin and Zetia in a joint venture, and the products have combined annual sales of about $5 billion.

The Enhance study examined Vytorin against Zocor alone in patients with a rare genetic predisposition to dangerously high cholesterol levels. Vytorin failed to halt the clogging of neck arteries better than Zocor alone, but it did a better job of reducing LDL cholesterol.

Beyond Vytorin, the FDA said it also would review "whether any changes to FDA's current approach to drugs that lower LDL cholesterol are warranted." High LDL is commonly believed to be a major risk factor for heart disease.

FDA officials cautioned the public not to turn away from cholesterol-lowering drugs.

"I think we have to be very cautious and not overreact to this one study," Dr. John Jenkins, head of the FDA's Office of New Drugs, told reporters.

Drugs that cut LDL are among the largest selling drugs in the world, and also include Pfizer Inc's Lipitor and AstraZeneca Plc's Crestor. Shares of Pfizer and AstraZeneca were also lower after the FDA announcement.

Lipitor, Zocor and other drugs in the same statin class have consistently shown the ability to reduce heart attacks and strokes by up to 30 percent.

Merck and Schering-Plough have been criticized by doctors, industry analysts and lawmakers for delaying presentation of results from the trial, which was concluded in 2006.

Deborah Cohn, a professor of marketing at Touro College Graduate School of Business in New York, said the delay in releasing the results had caused an understandable backlash.

"Consumers feel like there may be something else they're not telling us," Cohn said. "Nobody likes feeling like they're being lied to and that's how everybody's reacting."

Spokesmen for Merck and Schering-Plough both welcomed the FDA's statement.

Merck spokesman Christopher Garland said the FDA announcement "appropriately communicates information about the Enhance trial as well as information about Vytorin and Zetia."

Schering-Plough's Lee Davies said the FDA statement "puts appropriate perspective to the Enhance trial as well as commentary regarding safety and efficacy of Vytorin and Zetia in lowering LDL."

(Additional reporting by Lewis Krauskopf, Bill Berkrot, Kim Dixon and Ransdell Pierson, editing by Tim Dobbyn)

By Jim Christie

SAN FRANCISCO (Reuters) - California may be losing its chance to set the U.S. agenda for providing health care to millions of uninsured as lawmakers on Friday said a bill supported by Gov. Arnold Schwarzenegger to do just that is on its deathbed.

California's celebrity Republican governor has made medical insurance legislation a top priority and the bill before the state Senate, which votes on Monday, is a compromise crafted with Assembly Speaker Fabian Nunez, the top lawmaker of the Democrat-led chamber.

But some senators say they have heard enough to vote no on the legislation, which would require all Californians to have health insurance, either through private providers or subsidized state pool funded by taxes on cigarettes, hospitals and employers.

Millions lack medical insurance in the United States and California's efforts to provide it are being closely watched because it has has the largest state population, major political clout and the issue is front and center in a presidential election year where voters are anxious about rising health-care costs.

While the state Assembly was eager to advance the bill the Democrat-led Senate is very much undecided.

"Once fully implemented, over 70 percent of California's 5.1 million uninsured, most of whom are low-income working individuals and their families, including 800,000 children, will no longer be uninsured for health care," according to a statement on the bill from Nunez's office.

Republicans in the Senate's minority fear the bill will require near- and long-term tax increases, while Democrats in the Senate are concerned the bill is too vague to make good on its goals and could cost far more than initial estimates.

Schwarzenegger's administration is hopeful those concerns can be overcome by Monday's vote.

"We're continuing to talk, continuing to work," said Sabrina Lockhart, a spokeswoman for the governor. "This is a comprehensive plan that reflects hundreds of hours of work, if not thousands of hours, lots of compromise and feedback."

If the Senate approves the plan and Schwarzenegger signs it, voters would be asked to vote on it.

With state budget deficits forming for the remainder of California's current fiscal year and its next fiscal year starting in July, California can not afford an ambitious medical insurance experiment, said Republican state Sen. Tom McClintock.

"We're only $14 billion in debt. Let's add another $14 billion to that," McClintock said.

Democratic Sen. Sheila Kuehl said members of her caucus are concerned about the bill's cost, especially after the California's Legislative Analyst's Office, the state's budget watchdog, said the health program risked a $4 billion shortfall with five years.

"It gave members a lot of concerns," Kuehl said, adding that many lawmakers in the Assembly, which has approved the bill, gave little thought before endorsing it.

"Fifteen members in the Assembly, 15 Democrats, said to me they didn't even know what was in the bill," Kuehl said.

WASHINGTON (Reuters) - A drug used to treat bone marrow cancer may also help treat osteoporosis by stimulating stem cells, U.S. researchers reported on Friday.

They found that Velcade, made by Millennium Pharmaceuticals Inc to treat multiple myeloma, activated stem cells that differentiate into bone.

Tests in mice showed it apparently helps regenerate bone tissue and be may be a potential treatment for osteoporosis, a team at Massachusetts General Hospital and the Harvard Stem Cell Institute reported in the Journal of Clinical Investigation.

Harvard stem cell expert Dr. David Scadden said scientists have been hoping to find ways to use drugs to stimulate stem cells, which are the body's master cells.

"Stem cell therapies are often thought of as putting new cells into the body, but this study suggests that medications can turn on existing stem cells that reside in the body's tissues, acting as regenerative medicines to enhance the body's own repair mechanisms," Scadden said in a statement.

"Drugs that direct immature cells to become a particular cell type, like in this study, could potentially be very useful."

Velcade, known generically as bortezamib, stimulated mesenchymal stem cells, the researchers found. These cells develop into bone-building osteoblasts and several other types of cells including cartilage, fat, skin and muscle.

Tests in mice showed it increases the activity of osteoblasts, and when used in a mouse with osteoporosis it significantly improved bone formation and density.

"If the paradigm displayed in this study holds true for other tissues, we may have options for repairing and regenerating sites affected by injury or disease with medications -- that would be pretty exciting." Scadden said.

(Reporting by Maggie Fox; editing by Will Dunham)

By Julie Steenhuysen

CHICAGO (Reuters) - Celebrex, an arthritis drug in the same class as the recalled painkiller Vioxx, caused irregular heartbeats in fruit flies and in heart cells taken from laboratory rats, U.S. researchers said on Friday.

"When we tried this drug on the fly heart it became clear that it gave rise to very pronounced arrhythmia," said Dr. Satpal Singh, a pharmacologist at the State University of New York at Buffalo.

"It slows down and becomes irregular," said Singh, whose study appears in the Journal of Biological Chemistry.

He found the same effect in heart cells from rats.

Pfizer Inc's Celebrex is one of a class of painkillers that selectively block the COX-2 enzyme, which is involved in inflammation.

COX-2 inhibitors have drawn scrutiny since Merck & Co Inc pulled Vioxx from the market in 2004 after studies showed it raised the risk of heart attacks and stroke in long-term users.

Pfizer pulled a similar drug, Bextra, but has continued to market Celebrex, also known as celecoxib.

What surprised Singh and colleagues was that fruit flies known as Drosophila do not have COX-2 enzymes.

They looked further and found that the drug interfered with the passage of potassium in and out of heart cells through pores known as potassium channels.

"We found that one type of channel was very strongly inhibited in its function by the drug," Singh said in a telephone interview. "It is not clear if this channel plays a role in the human heart but it is present," he said.

Pfizer spokesman Jack Cox said while the study is interesting science, "It is important to be cautious about making a leap between this type of information and its effects in people."

"Abnormal heart rhythms and changes in electrocardiograms have been reported very rarely in clinical trials and in patients with Celebrex as well as with other non-steroidal anti-inflammatories (NSAIDs) such as ibuprofen and naproxen," he said in an e-mail.

"This information is already included in the Celebrex label."

Singh said the research, which was funded by the National Science Foundation, is preliminary and would need to be confirmed in humans.

He said the findings could not be extrapolated to other COX-2 drugs because the effect did not depend on its action on the COX-2 enzyme. "It is a completely unexpected mechanism. It begs for further study," he said.

Pfizer's Cox said the best way to assess the cardiovascular safety of NSAIDs is through a long-term, prospective clinical trial involving thousands of patients, which the company plans to undertake.

COX-2 inhibitors were invented as a safer alternative to aspirin and other NSAIDs, which can cause stomach bleeding.

(Editing by Maggie Fox and Stuart Grudgings)

By Carey Gillam

KANSAS CITY, Missouri (Reuters) - Matt Oglevie makes a good living as a self-employed house painter, is healthy and has no family to worry about. But he has been looking for a night job so he can get health insurance.

"I've got to have something. I've gone too long on my luck," said 37-year-old Oglevie.

Like Oglevie, an estimated 47 million Americans gamble daily that they won't suffer a major illness or injury and often go without needed medicine. With rapidly-rising health care costs, the number of uninsured has grown from 43 million in 2006.

U.S. lawmakers have argued over reform plans for years, and the spiraling problem is a hot topic in the 2008 presidential campaign with leading Democrats and Republicans alike acknowledging changes are needed.

But state leaders say they are tired of waiting for answers from Washington and at least a dozen states are trying to pass far-ranging health reforms this year.

"The list is very long of states that have made health reform a policy priority," said Laura Tobler, health policy analyst with the National Conference of State Legislatures.

"It isn't coincidental that the presidential candidates are also talking about health reform," said Tobler. "People on the street are pushing for reform."

Kansas Gov. Kathleen Sebelius, a Democrat, is one of several state-level leaders across the country who this month rolled out a reform proposal. Sebelius called for a $227 million health policy reform plan financed in part by a proposed $61 million increase in taxes on tobacco products.

Like many other states, the Kansas plan would encourage employer-provided health plans and expand existing programs for the poor and children. It would also increase wellness programs, pay physicians more for preventive services, and try to cut costs through standardizing record keeping.

'STATES CAN'T WAIT'

"The states can't wait for the federal government," said Marcia Nielsen, executive director of the Kansas Health Policy Authority. "The issue of rising health care costs are impacting families in their everyday lives. The federal government has really let us down."

Missouri's Republican Gov. Matt Blunt has launched a program to give uninsured people benefits comparable to those offered to state employees. The cost of the coverage is based on income, with a married couple earning $20,000 paying about $85 a month.

In Colorado, where roughly 800,000 are uninsured, workers would receive help from their employers. Low-income residents would receive subsidies to buy private coverage.

In California, Gov. Arnold Schwarzenegger is pushing one of the most aggressive measures -- a $14 billion health plan aimed at covering nearly all of the state's estimated 6.7 million uninsured.

Vermont has already set up a subsidized plan for uninsured residents to try to obtain universal coverage, while Massachusetts in July began requiring residents to have health insurance, while mandating that insurers accept all who apply.

Many factors have contributed to the growing number of uninsured, but experts say chief among them is the decline in employer-sponsored insurance plans that began in a 2001 economic downturn. The trend has left workers shouldering hefty private-pay premiums of hundreds or thousands of dollars a month, or going without.

Paying for health care directly has become increasingly out-of-reach for average Americans as costs for doctor visits, medicine and medical tests continue to outpace inflation and wage increases.

The U.S. Centers for Disease Control and Prevention reported last month that in 2005 19 million people did not get needed prescribed medicine, and 15 million did not get needed medical care due to cost. Health care spending in the United States totaled $2 trillion in 2005, a 7 percent increase from 2004, the CDC said.

(Editing by Maggie Fox and Vicki Allen)