Failed Drugs May Hold Other Cures

Wednesday, 31 Oct 2012 06:13 AM

 

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A failed prostate cancer drug might reverse Alzheimer’s. A former lung disease medicine may stop the ravages of muscular dystrophy. An experimental heartburn treatment may be better suited for treating a chronic cough.

Those are the ideas that scientists have come up with for compounds sitting on AstraZeneca Plc’s shelf that the company made available to academics through a partnership with the U.K.’s Medical Research Council. The council said Tuesday 15 research projects have been awarded 7 million pounds ($11.3 million) to study the drugs in animals or humans.

The collaboration is part of an effort by AstraZeneca to take a second swing at products that failed in clinical trials and are outside the areas it’s focused on in the past few years, such as cancer and cardiovascular disease. While the money involved is small, AstraZeneca hopes to unearth something big. There’s a precedent: Viagra, which Pfizer Inc. developed as a heart drug, was ultimately approved for erectile dysfunction and generated almost $2 billion in sales last year.

“We don’t want to leave value on the table outside of the core business,” Clive Morris, the AstraZeneca executive who heads up the effort to redevelop failed compounds, said in a telephone interview.

AstraZeneca’s effort is among the ways drug companies are trying to wring more value out of research. GlaxoSmithKline Plc said Oct. 11 it would publish all trial data, including for drugs that have failed, so that outside researchers can make new discoveries from it.

Research Setbacks

For AstraZeneca, the stakes are high: The company is under pressure to bring new products to market amid research setbacks and patents expirations on its best-selling drugs. By 2014 the company will have lost patent protection for medicines that account for more than 40 percent of sales, including Seroquel for schizophrenia and Nexium for ulcers, which together generated $10.3 billion last year.

In May, London-based AstraZeneca joined Pfizer and Eli Lilly in making dozens of compounds that failed in development available to U.S.-funded scientists for testing through the National Institutes of Health. If drugs are successfully developed, the companies and researchers will share sales and profit.

Any AstraZeneca program that’s discontinued is reviewed by Morris’s team of 30, who come from across the company’s research and development groups. Some experimental treatments aren’t worth spending more money on, while others might be, Morris said. The goal is to develop the assets at minimal cost and share the risk through academic or corporate partnerships.

Glaucoma Drug

The most advanced product to come from his team and to remain in house is AZD4017, a compound that AstraZeneca discontinued testing for diabetes and obesity in 2010 and is now being re-purposed in a mid-stage clinical trial for glaucoma as part of an agreement with Novartis AG. Another drug that was dropped after it didn’t meet goals of a study will reappear in the company’s development pipeline early next year for a new use.

Of the 22 compounds released by AstraZeneca to the MRC, zibotentan, an endothelin A receptor blocker, stood out to Seth Love, a professor at the University of Bristol, who studies Alzheimer’s. AstraZeneca terminated a late-stage study of the drug in advanced prostate cancer in February 2011 because it failed to stop the cancer from spreading.

Love has been looking at why Alzheimer’s patients have high levels of the vascular protein endothelin-1 in the brain and reduced blood flow there. He has found that a build-up of amyloid beta protein in the brain, a hallmark of Alzheimer’s, stimulates overproduction of enzymes that cause blood vessels in the brain to narrow, restricting blood flow and encouraging the disease to progress.

Blocking Enzymes

He and his team will study whether zibotentan, in combination with high blood pressure medicine losartan, can delay or reverse the progression of Alzheimer’s disease by blocking the enzymes and improving blood flow through the brain. Love said he will start with animal models before seeking approval to test the drug in patients.

“This is exactly what we’re looking for,” Love said in an interview. “The good thing is it’s a drug that’s been tested over a period of time in elderly people. We’re pretty hopeful the side effect profile isn’t too bad.”

The chance of finding a blockbuster among the relics may be slim. Still, it makes sense to reconsider a drug candidate if it was proven safe in early-stage trials and the patent life is sufficient, Elmar Kraus, an analyst with DZ Bank AG in Frankfurt, said in an interview. The process can be “both strenuous and potentially very rewarding,” he said.

“A clear advantage is that the company by then should have ample knowledge of how the drug is to be produced, stored, and administered, plus what the side effects are,” he said.

Copyright 2012 Bloomberg News

© HealthDay

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