Real Issues Resulting From Problems with the Drugs Vioxx, Galvus, Lunesta and TGN1412 Point To the Limitations of Animal Testing

Difficult To Precisely Translate From Animal to Human Results

The fact that the Wall Street Journal produced this piece signifies that this is a problem that is real. For years, campaigners against animal testing and the waste of resources and lives it results in have exposed the same truth – that literally, the physiological differences between species are different enough that animal testing is never a clear indicator of how a drug or chemical will react in the human body.

Hence, moving to more reliable non-animal tests such as Synthetic skin called Corrositex, Computer modeling, Improved statistical design, The Murine Local Lymph Node Assay (LLNA) and genetic arrays -- chips that can give a snapshot of the genetic effects of a drug (as mentioned below) or microarray chips, is not only more humane, but economical.

For more on the alternatives to the use of animals in drug testing, chemical testing, vivisection, etc. see http://www.geari.org/alternatives-to-animal-testing.html and The Johns Hopkins Center for Alternatives to Animal Testing at http://caat.jhsph.edu/.

To sum it up further, take a look at these quotes form the article below. You will clearly see real examples of drugs that passed animal tests, but that failed when tried on humans:

“Scientists agree, there's no way to precisely and consistently translate from animal to human results. After the withdrawals of the painkiller Vioxx and other medicines with side effects that didn't fully reveal themselves during years of testing, the need for such a translation looms particularly large.”

“In the case of the new Novartis drug Galvus, James Shannon, the company's global head of pharmaceutical development, told investors that Novartis researchers "do not understand -- do not know -- the mechanism of the skin findings" in monkeys. They do know that "humans appear to react to Galvus in a very different way."

“Another example of the confusing disparities that can arise in testing is the case of the popular sleep drug Lunesta. It won FDA approval despite the fact that tumors appeared when rats and mice took huge doses of a closely related chemical cousin of the medication. Some FDA reviewers were concerned enough initially to recommend rejection of Lunesta. After further analyses, however, agency officials concluded the data from human testing didn't suggest a signal for cancer in people. But you won't see the issue highlighted in the company's ubiquitous green-moth commercials for the drug.”

“It can happen that a product doesn't hurt animals, but turns out to be poisonous to patients. That occurred with the catastrophic British trial of an experimental biotech drug called TGN1412, meant to treat leukemia and other diseases. It didn't cause problems when given to monkeys and other species. Then six people took it in a small initial study and had life-threatening convulsions and organ failure. British regulators blamed an "unpredicted biological action of the drug in humans" that wasn't foretold by the "apparently adequate" preclinical studies.”


Article:

Recent Cases Point To the Limitations Of Animal Drug Tests

http://online.wsj.com/preview_login.html?url=http%3A%2F%2Fonline.wsj.com%2Farticle%2FSB117519602221153510.html%3Fmod%3Dyahoo_hs%26ru%3Dyahoo

By ANNA WILDE MATHEWS

March 30, 2007; Page B1

The promising diabetes drug Galvus recently got turned back by the U.S. Food and Drug Administration.

About 5,500 patients had taken the medicine in clinical trials at that point, but the problem apparently wasn't with them. The agency was worried because some monkeys who were given high doses of Galvus developed skin lesions. Humans who took normal amounts of the drug for as long as two years didn't get the sores, but the FDA refused to approve the drug until it saw more testing in people who might be at higher risk.

The decision spotlighted an important unresolved scientific question: What do the results of animal studies really tell us about humans? That question still puzzles researchers even though guinea pigs, lab rats and their brethren have long been part of experiments.

The FDA encourages work that could lead to a better understanding of human and animal genetics, and someday reduce the need for animal studies. Already, genetic arrays -- chips that can give a snapshot of the genetic effects of a drug -- allow researchers a broad, early-stage picture of what a drug does to an animal by illustrating which of its genes are "expressing," or activated, as a result of the medicine. Such signs typically show up well before the actual physical damage.

These genetic road maps can give a better idea of what's causing a safety worry in animal tests, and whether it is likely to affect people the same way. Still, the question remains: "Does that guarantee it won't have a toxic impact in humans?" asks Maneesh Jain, an executive at Affymetrix, a company that makes the microarray chips. "No."

In the pharmaceutical world, animal tests provide vital clues about experimental drugs and help prevent humans from being exposed to serious dangers. The animals are given far bigger doses than a person could likely tolerate, and are tested under circumstances that would be impossible with a human volunteer -- such as during pregnancy. That's why animal trials are still done, despite the concerns of animal-rights activists and others about the distastefulness and expense of sacrificing so many blameless critters.

Currently, the FDA is looking at results showing some anesthetic drugs led to neurological damage in young primates.

Before regulators approve a drug, it typically has been tested on hundreds of animals. The FDA requires initial testing in at least two species: one rodent, one nonrodent. By the end of the process, mice, pigs, rabbits, dogs, monkeys and other animals may have been used.

Animal tests at least give a broad sense of the effects of a drug. In one famous early example, a pancreatic extract successfully tested in diabetic dogs in 1921 helped to illuminate how insulin would help people with the disease. And many experimental medications are eliminated after very serious side effects show up.

Many times, however, subtle results in animals are unclear and scientists just don't know what to make of them.

In the case of the new Novartis drug Galvus, James Shannon, the company's global head of pharmaceutical development, told investors that Novartis researchers "do not understand -- do not know -- the mechanism of the skin findings" in monkeys. They do know that "humans appear to react to Galvus in a very different way."

Another example of the confusing disparities that can arise in testing is the case of the popular sleep drug Lunesta. It won FDA approval despite the fact that tumors appeared when rats and mice took huge doses of a closely related chemical cousin of the medication. Some FDA reviewers were concerned enough initially to recommend rejection of Lunesta. After further analyses, however, agency officials concluded the data from human testing didn't suggest a signal for cancer in people. But you won't see the issue highlighted in the company's ubiquitous green-moth commercials for the drug.

It can happen that a product doesn't hurt animals, but turns out to be poisonous to patients. That occurred with the catastrophic British trial of an experimental biotech drug called TGN1412, meant to treat leukemia and other diseases. It didn't cause problems when given to monkeys and other species. Then six people took it in a small initial study and had life-threatening convulsions and organ failure. British regulators blamed an "unpredicted biological action of the drug in humans" that wasn't foretold by the "apparently adequate" preclinical studies.

It isn't clear how to avoid such fiascos. For now, regulators aren't likely to dial back preclinical study requirements. "At the moment, we don't have a better way of doing it," says David Jacobson-Kram, associate director of pharmacology and toxicology in the FDA's drug center. Neither has the agency increased its focus on animal studies, despite drug-industry concerns sparked by the Galvus decision.

Scientists agree, there's no way to precisely and consistently translate from animal to human results. After the withdrawals of the painkiller Vioxx and other medicines with side effects that didn't fully reveal themselves during years of testing, the need for such a translation looms particularly large.