March 11 (Bloomberg) -- Amgen Inc.'s and Johnson & Johnson's anemia drugs are tied to increased risks of death and faster- spreading tumors at high doses, a finding that may require new restrictions on the medicines, U.S. regulators said.

Amgen's Aranesp and Epogen and J&J's Procrit showed greater risks for patients with cancers of the breast, head and neck, lung, and cervix in eight clinical trials, said staff of the U.S. Food and Drug Administration in briefing documents posted today on the agency's Web site. An FDA advisory panel will consider benefits and risks of the products March 13 in Gaithersburg, Maryland.

Amgen, the world's largest biotechnology company, lost $29 billion in market value last year after Aranesp, its top seller, and Epogen were tied to higher risks of heart attack, stroke and death at high doses. The FDA urged doctors a year ago to use the lowest doses possible, and the agency updated safety warnings on the drugs' prescribing information last week.

``There is now mounting evidence of documented effects on survival, tumor progression'' and blood clots, FDA staff said in the report today. The evidence ``requires a re-assessment of the net benefits of this class of drugs.''

At the most extreme, the panel may recommend an end to use of the drugs for patients whose anemia is caused by cancer chemotherapy, allowing continued marketing mostly for kidney disease patients. The committee also may suggest halting use of the products for certain types of patients found to be at greater risk, the FDA staff said. The agency may seek voluntary restrictions on advertising of the products and on offering incentives to doctors, according to the staff.

No `Surprises'

``As harsh as the questions sound, in our view, they do not contain any surprises,'' said Michael King, an analyst with Rodman & Renshaw in New York, in a note to clients today. ``We maintain our perspective that there is only a 10 percent chance that Aranesp will be completely contraindicated,'' or prohibited, for use among cancer patients.

Amgen fell 6 cents to $44.62 at 4 p.m. New York time in Nasdaq Stock Market composite trading. Amgen, based in Thousand Oaks, California, has dropped 27 percent in the past 12 months. J&J rose $1.11, or 1.8 percent, to $62.44 on the New York Stock Exchange.

Recommended Doses

There is ``insufficient evidence'' to rule out risks from the anemia drugs at recommended doses, because all of the trials showing danger were performed at higher-than-recommended doses, the FDA staff said. One trial was designed in 2004 to examine safety at recommended doses, although patient enrollment in the study has been slow so it will take ``many years'' to see a result, according to the staff report.

``The uncertainty regarding the risks of ESAs when used in accordance with product labeling has not been satisfactorily addressed in the four years since'' another advisory committee reviewed the drugs' safety, the FDA said. The drugs are known as ESAs, or erythropoeisis-stimulating agents, which boost production of oxygen-carrying red blood cells.

The warning added March 7, the strictest used by regulators, cites new evidence from a breast cancer study, called Prepare, which showed patients had a higher risk of death on Aranesp. It also notes danger for patients with cervical cancer, based on results in December from a study called GOG-191. The label previously included similar warnings for patients with cancer of the breast, lung, head and neck, and lymph nodes.

Physicians' Group

Until it sees peer-reviewed data, the American Society of Hematology, a physicians' group, said in an e-mailed statement it ``does not see sufficient evidence of harm to support recommending complete cessation'' of the anemia drugs for all cancer patients.

The hematology group, along with the American Society of Clinical Oncology, issued new prescribing guidelines in October based on a three-year review of clinical trials. The physicians said Medicare, the U.S. health insurance program for the elderly and disabled, went too far in restricting use of the products.

The anemia drugs are used to treat the weakness and fatigue of patients who have chronic kidney disease or are undergoing cancer chemotherapy.

Aranesp generated $3.61 billion in worldwide sales in 2007, a 12 percent decline from the previous year. Epogen, marketed for patients on kidney dialysis, generated $2.49 billion in U.S. sales in 2007, down less than 1 percent from the prior year.

50 Clinical Trials

Procrit, manufactured by Amgen and identical chemically to Epogen, is marketed by J&J in the U.S. under a license. Procrit had $1.69 billion in U.S. sales in 2007, an 18 percent drop from the previous year. It is sold for people with cancer and kidney patients not on dialysis.

About 50 clinical trials have measured survival time for patients on the anemia drugs, with the eight studies from the past five years suggesting the medicines raise the risk of death, or are linked to faster tumor growth, Amgen and J&J said in their briefing document for the FDA panel. The risks were seen when the drugs were given for unapproved uses, including higher-than- recommended doses, the companies said.

A pooled analysis of 8,000 patients from clinical trials shows the drugs don't raise the risk of death, the companies said.

``When we look at the totality of all the studies, we don't see an increase in mortality,'' said Peter Bowers, senior director of clinical research for J&J Oncology Research and Development, in a March 7 interview.

`Maximize Benefits'

``Amgen strongly believes that ESAs provide an important clinical option for some patients'' and will work with the FDA ``to maximize the benefits of these drugs when used according to the approved labeling while minimizing the risks,'' the company said today in an e-mailed statement.

The safety issues have raised concerns, and the companies are committed to further study, Amgen and J&J said in their briefing documents prepared for the FDA panel. New studies will measure safety of the products at the recommended doses, Bowers said. The companies are also supporting studies to examine whether the anemia drugs stimulate tumor growth, he said.

There are risks if the FDA acts to curb use of the products, the companies said. More people may need blood transfusions, putting a strain on the nation's blood supply, the companies said. Emerging infectious diseases could also be passed along unwittingly through transfusions, Bowers said.

To contact the reporter on this story: Luke Timmerman in San Francisco at ltimmerman@bloomberg.net.

Last Updated: March 11, 2008 16:11 EDT