WASHINGTON, Oct 15, (Agencies):  The United States is considering new restrictions on widely used anemia drugs that appear to double the risk of stroke in patients with kidney disease.
The Food and Drug Administration posted its safety review of the three blood-boosting medications from Amgen Inc. on Thursday, focusing on their use in patients with chronic kidney disease who are not yet sick enough to receive dialysis.

The medicines — Procrit, Aranesp and Epogen — are multibillion dollar sellers because of their ability to boost oxygen-carrying red blood cells, reducing the need for painful blood transfusions. But sales have fallen sharply since 2007, when the FDA added the first of several safety warnings to the drugs, based on evidence they can cause tumor growth and hasten death in cancer patients. The drugs are no longer used in patients with several types of cancers.

Anemia, which causes weakness and shortness of breath, is a side effect of chemotherapy and kidney failure.

Now the FDA is reviewing a study published last year that showed kidney disease patients taking Aranesp were twice as likely to experience stroke compared with those taking a dummy treatment. The goal of the study was to show that the drug could prevent heart attack, stroke and other heart-related problems, as had been assumed for years.

But FDA reviewers, using the chemical name for Aranesp, said in their posting that the “evidence raises considerable doubt about the safety and advisability of using darbepoetin in this manner.”
Amgen has argued that its drugs should continue to be used because they help avoid blood transfusions, which carry their own risks. But the FDA’s scientists point out that 15 percent of patients who took the company’s drug still needed transfusions, compared with 25 percent of those taking a placebo treatment.

“Treatment did not eliminate the risk of requiring (red blood cell) transfusions,” states the FDA review.
On Monday the agency will ask a panel of outside experts to review the data and make recommendations on how to safely use the drugs. Panelists could recommend bolstered warning labels, additional studies or lower doses of the drugs. The FDA is not required to follow the group’s advice, although it often does.

Amgen, based in California, makes all three drugs. Procrit is sold by Johnson & Johnson’s Centocor Ortho Biotech division, under a long-standing agreement between the companies.
Last year the drugs — known as erythropoiesis stimulating agents — had combined sales of $6.3 billion, according to health data firm IMS Health.

Pre-dialysis kidney patients contributed 30 percent of Aranesp’s revenue last year, estimates Robyn Karnauskas, an analyst at Deutsche Bank. New FDA restrictions would shave $86 million in sales off the drug, he estimates, which would have a minimal effect on Amgen’s revenue. Amgen, one of the giants of the biotech drug industry, had total revenue exceeding $14.6 billion last year.

Roche Hepatitis C: Two experimental drugs — one of them belonging to Switzerland’s Roche — appear to be safe and well-tolerated by hepatitis C patients when used in combination, researchers reported on Friday.
The search for new treatments for hepatitis C has gained urgency because the present cocktail — interferon and ribavirin — has serious side effects and a growing number of people do not respond to interferon anymore.
In a paper published in The Lancet, researchers in Australia, New Zealand and the United States said patients who were given the two experimental drugs — danoprevir and Roche’s RG7128 — appeared to tolerate the combination well.
A total of 88 patients in Australia and New Zealand participated in the 13-day phase 1 trial, of whom 14 were given placebo, or drugs with no therapeutic effect.
The rest were divided into seven groups and given both drugs in different dosages.
Patients who were given the highest doses — 1,000 milligrams of RG7128 and 900 mg of danoprevir twice daily — showed huge reductions in viral loads by day 13.
“Our study was to combine two different drugs with two different mechanisms of action; they target different parts of the virus,” said professor Edward Gane of Auckland City Hospital and Auckland District Health Board in New Zealand.
“We wanted to see if we can prevent emergence of resistance and suppress the virus and this is certainly what was shown. There were no cases of resistance in this study.”
Viral loads for several of the patients given the highest doses fell to below detection levels, they said in the paper.
Gane said neither drug should be used in isolation because of the speed at which this virus mutates.
“When you use these drugs by themselves, even though they are very well tolerated and have very little side effect, the virus rapidly mutates and becomes resistant to them,” he said.
The patients complained of headache, lethargy, rash, gastrointestinal disorders and nausea but they were mild to moderate, the researchers said.
Worldwide, more than 170 million people are infected with the hepatitis C, a disease that can result in liver cirrhosis, or hardening, and finally liver cancer.
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Kidney stones: A new technique to curb the growth of crystals in one type of kidney stone offers hope for preventing development of the hard deposits which can cause extreme pain, researchers reported Thursday.
Scientists at New York University’s Department of Chemistry and its Molecular Design Institute, NYU School of Medicine, and the Medical College of Wisconsin sought to attack kidney stones at the molecular level by examining the crystals that form them.
The researchers used atomic force microscopy, which allows for the observation of objects as small as a nanometer, to observe the growth of the L-cystine crystals that make up one type of kidney stone.
Knowing how these crystals grew, the researchers could then select a chemical agent to inhibit this process.
“This may lead to a new approach to preventing cystine stones simply by stopping crystallization,” said Michael Ward, one of the authors of the research and chair of NYU’s Department of Chemistry.
“Moreover, these findings are an example of the significant advances that can be achieved through collaborations between researchers in physical sciences and in medicine.”
Kidney stones comprised of L-cystine affect an estimated 20,000 individuals in the United States.
This number is smaller than the number of Americans afflicted by calcium oxalate monohydrate (COM) stones, but L-cystine stones are larger, recur more frequently, and are more likely to cause chronic kidney disease.
Although they often cause no permanent damage, kidney stones can be extremely painful and sometimes are removed by surgery or sound waves.
Current medications for L-cystine stone prevention can cause adverse side effects such as nausea, fever, fatigue, skin allergies, and hypersensitivity.
The findings of the latest research appear in the October 15 issue of the journal Science.