Novartis' Zometa Cuts Risk of Breast Cancer Returning

May 31 (Bloomberg) -- Novartis AG's bone-strengthening drug Zometa unexpectedly cut the risk that breast tumors would return in a study of young women getting the therapy, which protects bones from the ravages of cancer.

The trial, showing just two injections a year of Zometa slashes cancer recurrence by 35 percent, offers a novel way to fight cancer and expands the market for the medication. Novartis, Switzerland's second-largest drugmaker, currently sells Zometa to treat malignancies that spread to the bone. It also is used at a lower dose for osteoporosis.

Breast cancer, the most common tumor in women, will be diagnosed in more than 180,000 patients in 2008, according to the American Cancer Society. In the study of 1,803 patients, about 6 percent of women getting Zometa suffered a relapse within five years, compared with 9 percent who didn't receive the drug, according to the study presented at the American Society of Clinical Oncology meeting today in Chicago.

``We have shown we can keep the cancer away, and that is great news for patients,'' lead author Michael Gnant, professor of surgery at the Medical University of Vienna, said in an interview. ``Future research will focus on optimizing the administration schedule and the dose, and determining which patients will benefit the most from treatment.''

Novartis, based in Basel, Switzerland, sells Zometa in more than 80 countries and helped fund the study. It is the first to show the medication can slow cancer in addition to protecting bones. Women getting the drug had fewer problems with all types of recurrences, including local and distant disease, tumors in the opposite breast and in the bone, the study found.

Hormone-Fueled Cancer

While it is not clear how Zometa slows cancer, researchers think it is because it makes the cell environment hostile to malignant cells, Gnant said.

The study involved younger women who hadn't gone through menopause and had early stage breast cancer that was fueled by hormones. All patients were given treatment to suppress their ovaries. They also were given the generic drug tamoxifen or AstraZeneca Plc's Arimidex, with or without Zometa.

There were no differences in results between patients getting tamoxifen and Arimidex, the study found. AstraZeneca also funded part of the research.

Few women in the study received chemotherapy, once a standard treatment. The results show many women with early stage disease may fare well without chemotherapy, said Eric Winer, professor at Harvard Medical School and director of the breast oncology program at the Dana-Faber Cancer Institute in Boston.

Other Cancers

Zometa may also benefit post-menopausal women and patients with other types of cancer, Gnant said.

There were no cases in the study of osteonecrosis, which causes jaw-bone damage, or kidney harm, side effects linked to drugs like Zometa.

Zometa, which belongs to a group of drugs called bisphosphonates, is thought to reduce cells' ability to travel and stick to each other and the bone, to stimulate cancer fighting immune cells, choke the growth of blood vessels that feed cancer cells and cause cells to self destruct.

Zometa had first-quarter sales of $331 million. It's also sold as Aclasta and Reclast in the U.S. and in Europe as an infusion to treat osteoporosis.

A New Use

Zometa isn't widely used now for osteoporosis because the drug is given intravenously, and most general practitioners don't have the infusion capabilities needed to administer it, said Julie Gralow, chair of ASCO's communications committee and associate professor at the University of Washington. Cancer doctors do have the equipment, and the study findings are likely to dramatically boost use of the drug, she said in an interview.

``I think this will change practice,'' Gralow said. ``It will get great uptake in the U.S.,'' she said.

Though the study included only premenopausal patients with hormone-sensitive breast cancer, the drug is exceedingly safe and will likely be given to a wide range of breast cancer patients, she said.

Another, broader study including women before and after menopause getting a variety of cancer treatments is under way, Gralow said. The results of the study, using a more intensive dose of Zometa, will be available by the end of the year.

Until those results are available, it would be a mistake to prescribe the drug widely for all women with breast cancer, Winer said.

Between 20 percent and 25 percent of breast cancer patients are premenopausal, Winer said. Half of them have tumors that are fueled by hormones, or about 25,000 women a year, he said.

``In my humble view, it's entirely the wrong message that all women should be getting this drug starting tomorrow,'' he said in an interview. ``It's not a terribly toxic drug, but all drugs have toxicities. Within the narrowly defined group of women who got the drug, this study would give one strong impetus to use Zometa.''

To contact the reporters on this story: Eva von Schaper in Munich at evonschaper@bloomberg.net;

Merck KGaA's Erbitux Drug May Get Edge on Avastin

May 29 (Bloomberg) -- A single gene may help Merck KGaA and ImClone Systems Inc. find which patients are best treated with their Erbitux cancer drug, helping gain an edge over Roche Holding AG and add 600 million euros ($938 million) in sales.

Merck may win European backing as soon as today to sell the medicine for deadly bowel tumors that have spread throughout the body. Results of a study to be released June 1 may show the drug is especially useful for the 60 percent of colorectal cancer patients who carry an intact version of a gene called kras.

Data that enable doctors to link the kras gene to successful treatment may change the way oncologists treat the cancer, increasing the use of Erbitux and allowing it to compete against Roche's Avastin, said Amit Roy, an analyst at Citigroup. Avastin, the first of a new generation of targeted drugs to win approval for treating malignant bowel cancer, generated $3.4 billion for Basel, Switzerland-based Roche last year.

``Erbitux is very impressive,'' Dirk Jaeger, an oncologist at the University of Heidelberg said. ``We can already say it is as good if not better than Avastin for patients that carry unmutated kras.''

Jaeger routinely employs a test that can cost about 120 euros to detect the version of kras a patient carries. The new research, to be presented at the American Society of Clinical Oncologists meeting in Chicago, may persuade other doctors to follow the same procedure.

Shares Gain

Darmstadt, Germany-based Merck rose 43 cents, or 0.5 percent, to close at 92.71 euros in Frankfurt trading today. The stock has gained more than 7 percent this year on optimism Erbitux may win wider use against colon cancer. Investors are also awaiting results of a clinical trial to be presented at the research meeting that may show that Erbitux may extend survival of lung cancer patients longer than the average eight weeks already shown in studies of Avastin.

The shares of Roche, which developed Avastin with South San Francisco, California-based Genentech Inc., have dropped about 8 percent in the period.

``Avastin works regardless of kras status - it is the only option for patients with mutated kras and the best option for patients with wild-type kras,'' Roche spokesman Alexander Klausner said in an e-mailed message.

Erbitux is approved to treat head and neck tumors as well as colon cancer that has progressed despite treatment with other drugs. Merck, which bought non-U.S. rights from New York-based ImClone in 1998, is conducting research in other tumor types and for wider use of the medicine to capture additional sales. The German drugmaker was the first to win approval for Erbitux when Swiss regulators cleared the treatment for sale in December 2003.

Crystal Trial

ImClone shares fell 30 cents to $42.82 in Nasdaq Stock Exchange trading.

Results last year of the so-called Crystal trial, which the German drugmaker used to support the European application to market Erbitux against colon cancer, showed the treatment slowed the disease's progression by 28 days compared to conventional drug therapy. Morgan Stanley analyst Andrew Baum said this advantage may still not be enough for European regulators to make Erbitux a first-choice treatment over Avastin.

To find those patients who may respond best to Erbitux, researchers examined tissue removed from people enrolled in the Crystal trial to test whether their tumors contain an intact or mutated version of the gene.

Speculation

Other smaller studies have suggested that the cancer may progress more slowly in patients with a normally functioning kras gene who are treated with Erbitux and Amgen Inc.'s Vectibix. That has prompted speculation the same effect may also be demonstrated in the Crystal trial.

``Kras is important, it helps us to tell in advance who will benefit,'' said Eric van Cutsem, an oncologist at the University of Leuven in Belgium, who led the Crystal study.

Kras signals the body to make a protein linked to the growth of cells. In some tumors, the so-called ras pathway goes haywire, telling cells to multiply non-stop. Erbitux can help halt the message if the kras protein is intact. The drug doesn't work when the kras is damaged, the Crystal study may show. Scientists don't know why the gene gets damaged in certain patients.

The ability of Erbitux to take on Avastin depends on how long the medicine can stall the disease. The benefit of one over the other is difficult to judge based on available data because each was paired with different chemotherapy treatments in clinical trials, Jaeger said.

Man-Made

Citibank's Roy said patients with normal kras should have an even better response than the 28-day benefit seen in the Crystal trial. Those patients could see their cancer stop growing for as long as 1.5 months, he said in a note to clients.

``It will take away sales slowly at first, but we do expect Avastin to suffer,'' Markus Mayer, an analyst at UniCredit SpA in Munich said. Mayer raised his Merck rating to ``buy'' from ``hold'' on May 19.

Erbitux is a man-made antibody, a substance naturally produced by the immune system in response to infection. The drug works by latching onto cancerous cells and blocking replication. The flaw in the kras gene, which holds the blueprint for part of a messaging system inside the cell, is thought to render Erbitux ineffective.

Data that prove Erbitux works in people with a normally functioning kras gene would allow doctors to find the most- suited patients and offer health-care payers a way to save costs, analysts say.

``This is good for patients, good for doctors and good for us,'' said Oliver Kisker, who leads the clinical development of a group of cancer drugs at Merck, in an interview. ``This really differentiates us from the competition.''

To contact the reporter on this story: Eva von Schaper in Munich at evonschaper@bloomberg.net.

Amgen says osteoporosis drug tops Merck's in trial

NEW YORK -

Biotechnology company Amgen Inc. said Wednesday that a head-to-head study showed its late-stage osteoporosis drug denosumab was more effective than a competing drug from Merck & Co.

Amgen said that in a study of 1,189 postmenopausal women, denosumab showed greater improvement in bone mineral density at various skeletal sites, including the hip and spine, compared to Merck's Fosamax. Results were presented at a medical conference in Barcelona, Spain.

The results mirrored those of a head-to-head trial released May 19 among women who were transitioned from Fosamax to denosumab.

Denosumab is given twice a year as a subcutaneous injection, while Fosamax is taken once a week as a pill.

Amgen also said it is awaiting results from a late-stage trial expected later this year examining anti-fracture efficacy that it will use to support a denosumab application with the Food and Drug Administration.

NEW YORK -

Biotechnology company Amgen Inc. said Wednesday that a head-to-head study showed its late-stage osteoporosis drug denosumab was more effective than a competing drug from Merck & Co.

Amgen said that in a study of 1,189 postmenopausal women, denosumab showed greater improvement in bone mineral density at various skeletal sites, including the hip and spine, compared to Merck's Fosamax. Results were presented at a medical conference in Barcelona, Spain.

The results mirrored those of a head-to-head trial released May 19 among women who were transitioned from Fosamax to denosumab.

Denosumab is given twice a year as a subcutaneous injection, while Fosamax is taken once a week as a pill.

Amgen also said it is awaiting results from a late-stage trial expected later this year examining anti-fracture efficacy that it will use to support a denosumab application with the Food and Drug Administration.

Merck drug reduces bone breakdown in cancer patients

CHICAGO -

Drug maker Merck & Co. on Tuesday said a mid-stage trial of an osteoporosis drug in women with breast cancer reduced the breakdown of bone.

Patients treated with the drug, odanacatib, showed a 77 percent reduction from baseline in bone breakdown compared to 73 percent of those treated with Novartis AG's Zometam, Merck said. Women with breast cancer are often susceptible to cancer spreading to bones, a condition known as bone metastases

Whitehouse Station, N.J.-based Merck said that results from the trial would be presented June 3 at the American Society of Clinical Oncology conference.

Merck added that it would conduct late-stage studies of odanacatib in both breast and prostate cancer based on the results.

Odanacatib is already in late-stage trials for the treatment of osteoporosis.

Shares of Merck rose 42 cents to $39.16 in morning trading.

Novartis Looks For Magic Pill

LONDON -

The Swiss drugmaker Novartis has been given the green light by the European Commission to sell Extavia, a multiple sclerosis drug. And although the firm has good reason to be happy, it shouldn’t be overjoyed as it faces tough competition.

Norvartis (nyse: NVS - news - people ), whose largest division of pharmaceuticals develops and manufactures prescription drugs to treat various diseases, said it will launch Extavia in the United States and Europe in the first half of next year.

But analysts warn the company will struggle to make ends meet in an already crowded market, prompting its shares to hardly move. Novartis shares rose 0.4%, or 2 cents, to $53.03 in morning trading in New York.

“It is difficult to know what market percentage Novartis is going to achieve with this new drug,” Tom Muller, an analyst with Theodoor Gilissen, told Forbes.com.

“They have to start from scratch. It will take them at least a couple of years to have a strong position in the market with solid competitors,” Muller said.

One of Novartis main rivals is German drugmaker Bayer (nyse: BAY - news - people ), which produces an already effective MS drug treatment of MS, Betaseron.

Novartis and Bayer settled a dispute over Betaseron in a deal that gave Bayer full control of the product while allowing Novartis to launch a version in 2009. Bayer's sales have been affected by copycat versions of its drugs in America and Europe.

Extavia is the first in a new portfolio of medicines from Novartis that is planned to include both established treatments and innovative therapies for patients with MS, the group said.

Multiple sclerosis, a progressive and debilitating disorder caused by the destruction of myelin, is the most common disorder of the central nervous system in young adults.

Genentech, Biogen's Rituxan fail late-stage lupus study

NEW YORK -

Biotechnology companies Genentech Inc. and Biogen Idec Inc. said Tuesday their drug Rituxan failed a late-stage study involving lupus patients.

The drug, which is already approved to treat non-Hodgkins lymphoma and rheumatoid arthritis, failed to prompt a response in patients when compared with placebo in the 52-week study.

The drug also failed to meet any of its six secondary goals.

"We are disappointed in the results of this Phase II/III study, but we understood from the outset the significant challenges in developing treatments for systemic lupus erythematosus," said Dr. Hal Barron, Genentech (nyse: DNA - news - people )'s senior vice president of development and chief medical officer, in a statement.

The company has another ongoing late-stage study on lupus nephritis patients and said that will continue. Lupus nephritis is an inflammation of the kidney caused by lupus, a chronic inflammatory disease. Results from that study are expected in the first quarter of 2009.

Shares of Cambridge, Mass.-based Biogen fell $2.75, or 4.3 percent, to $61.92 in morning trading Tuesday.

Shares of South San Francisco, Calif.-based Genentech fell $3.25, or 4.4 percent, to $69.91.

Study says FDA allowed risky tests of blood substitutes

CHICAGO -

Experimental blood substitutes raised the risk of heart attack and death, yet U.S. regulators allowed human testing to continue despite warning signs, says a scathing new report.

The U.S. Food and Drug Administration fell short, the report contends, even as red flags popped up during studies by five biotech companies. Rules barred the agency from releasing company trade secrets, and that kept some information hidden and may have led to unnecessary heart attacks and deaths, wrote the authors, who are government scientists and consumer advocates.

"There shouldn't be secret science," said the lead author of the report, Dr. Charles Natanson, of the National Institutes of Health Clinical Center. Safety data need "to be made public expeditiously so science can build on the mistakes" of previous research, he said.

The report, being published online Monday by the Journal of the American Medical Association, is the latest analysis of the risks of blood substitutes, which have been in testing for more than a decade.

It was written by scientists with the NIH Clinical Center and advocates with the watchdog group Public Citizen. The clinical center in Bethesda, Md., seeks to ensure the safe and ethical conduct of clinical research.

A safe replacement for blood would be a breakthrough for medicine and a big money-maker for companies that produce it. It could save lives on battlefields. Unlike ordinary blood, it could, theoretically, be stored for years without refrigeration. It also would work with any blood type and would not carry infections like hepatitis or the AIDS virus.

By the end of 2000, a dozen studies of blood substitutes had been completed. By then, FDA officials would have known enough about cumulative risks to put a halt on further experiments, the JAMA report contends.

But the FDA looked at each product and each use separately - in surgery, in trauma, in stroke patients - rather than pooling the results to get a fuller picture of the risk, Natanson said.

In 2006, after a lawsuit by Public Citizen protesting a closed-door hearing, the FDA halted a test by the Navy, which planned to use a blood substitute on civilian trauma victims. Such tests raised ethical concerns about giving trauma patients an experimental product without their consent.

Dr. Jay Epstein, director of FDA's office of blood research and review, defended the agency's decisions about human testing of the products despite risks. The agency has found enough differences among the individual products and their intended uses to allow some studies to proceed, Epstein said Friday in a conference call with reporters.

Currently, there are no approved blood substitutes or clinical studies of them in the United States. However, American companies are testing them on people in South Africa and seven European countries. South Africa has approved one of the products, Hemopure, made by Biopure Corp. (nasdaq: BPUR - news - people ), based in Cambridge, Mass., for use in anemic surgery patients.

"It is highly unlikely, I'd say impossible, that any of these countries are aware of the risk," said study co-author Dr. Sidney Wolfe of Public Citizen.

In the new report, researchers analyzed 16 randomized controlled studies of five different blood substitutes. More than 3,700 patients were involved. The studies included elective surgery, trauma and stroke patients.

Researchers found a 30 percent higher risk of death overall for patients who received transfusions using the blood substitutes; 164 of those patients died. Among those who received ordinary blood products or saline transfusions, 123 died.

The risk of heart attack was nearly tripled in the groups receiving blood substitutes. There were 59 heart attacks in that group compared with 16 heart attacks in the group that didn't get the new products.

Experts speculate that hemoglobin in the blood substitutes scavenges nitric oxide from the blood, causing blood vessels to constrict and sticky platelets to build up. That increases the risk of heart attacks.

The report comes as the besieged FDA reacts to numerous other troubles.

Contaminated blood thinner from China recently highlighted the agency's shortage of inspectors abroad. In September, an inspector general's report found the FDA does little to oversee human safety in clinical trials by drug companies.

Last year, new legislation was adopted to give the FDA more power to act when problems emerge with drugs already on the market - action prompted by the furor over the withdrawal of the risky painkiller Vioxx in 2004.

Even with the new law, the FDA needs more financial support, Natanson said.

"They're hardworking people. They're trying their best," he said. "If we really want them to be an agency that is going to protect us, we need to support them."

But companies may be withholding key information from the FDA, said one former biotech employee.

Dr. William Hoffman, former chief medical officer at Biopure, left the company in 2000 after management prevented him from telling the FDA that he believed one of the company's studies should be stopped. Hoffman said Biopure management has changed since then.

"The FDA knows more than anyone at any of the individual companies, but they may not know the whole story," Hoffman said. "There may be information withheld from the FDA."

Most developers of blood substitutes are one-product companies, and their existence depends on the fate of the product, said Hoffman, now director of cardiac-surgery critical care at Massachusetts General Hospital in Boston.

"Drug development is expensive. In order to get a drug to market you have to keep good news coming out so the value of the company remains high," Hoffman said.

Two companies whose products were included in the new report called the analysis flawed.

"There are vast differences among these products that make any pooling of data flawed, especially across different clinical experiences," Biopure vice president Dr. A.G. Greenburg wrote in an e-mail.

Dr. Steven Gould, CEO of Evanston, Ill.-based Northfield Laboratories Inc. (nasdaq: NFLD - news - people ), said in a statement that pooled analysis can be "a useful tool to raise questions" involving a class of drugs, but is "not designed to provide answers about specific products or to examine fully the risk-benefit ratio of any particular product."

Gould said Northfield would present a summary of research on its product, PolyHeme, at an FDA discussion of the safety issues this week.

In disclosures required by JAMA, Natanson reported that he is an unpaid consultant to the FDA on Hemopure and was once paid $10,000 to review a blood substitute study by Hemosol Corp. of Canada.