Animal tests are unreliable indicators of drug safety

Animal tests are unreliable indicators of drug safety

Two major pharmaceutical companies have made headlines this week for major catastrophies involving drugs which had been predicted to be safe and even beneficial to humans in animal tests.



American pharmaceutical company Merck has lost in a case brought by two co-plaintiffs who alleged that the company failed to warn users of its 'breakthrough' pain-killer Vioxx of the drug's dangerous heart-related side-effects.

A New Jersey jury awarded a 77-year-old man $4.5m in compensation after it found that Vioxx had substantially contributed to the heart attack suffered by John McDarby. According to news sources, Merck has also been found to have "misrepresented and concealed" the major risks when marketing the drug to doctors.

The decision is of particular significance because, while past cases involved patients who had used Vioxx for a short-term period, this was the first case involving patients who were long-term users. It may be an indicator of how future cases, of which there are a total of about 9650 pending, will play out in courts across the United States.

Merck voluntarily pulled the $2.5 billion a year drug from the market in September 2004 after a study showed it doubled the risk of heart attack and stroke among people who used it for at least 18 months.

In a separate and pending lawsuit filed in July 2005 by the Physicians Committee for Responsible Medicine, or PCRM, Merck is accused of relying on animal studies as the basis for claims that the drug was safe, despite clinical tests such as the "Vigor" study ordered by the Food and Drug Administration on humans showing contrary results.

The lawsuit contends that Merck was aware of the limitations of animal testing, which are often inconsistent, species-dependent, and not useful in predicting drug safety or efficacy in humans. In studies involving rodents, at least nine of 11 mice and rat studies showed Vioxx to be beneficial for animal hearts; evidence of which was later used to market the drug as potentially beneficial for human hearts. The suit also states that Merck knew of more effective safety assessment methods, such as postmarket surveillance of patient reactions, in vitro tests using human cells and tissues, and computer modeling, but failed to employ these methods.

Merck endangered public health by relying on inapplicable animal tests rather than relevant and available human data, said Dan Kinburn, PCRM associate general counsel.

And while Merck begins its long journey through the courts, German pharmaceutical company TeGenero, maker of the experimental drug TGN1412, is still trying to find what went wrong in its clinical trial of the drug which left six men seriously ill in a London hospital in March.

According to a report by the Medicines and Healthcare products Regulatory Agency (MHRA), "no human error in any part of the protocol" was found.

The MHRA further reported that the problem appeared to be due to an unprecedented biological reaction to the drug in humans which had not been seen previously on tests in animals.

"Our main conclusion is that there was a powerful pharmacological action of this drug in man which was not detectable in the pre-clinical studies done in the non-human primate species, even in far-higher doses," said MHRA Chief Executive Professor Kent Woods.

The drug had previously been tested on rabbits and monkeys, who were given several times the dose given to the six men.

TGN1412 was designed to treat chronic inflammatory conditions and leukaemia.

The MHRA, along with TeGenero reiterated that Even in hindsight, we can see no evidence of any such adverse reactions from the preclinical studies. The doses given to the humans in the trial were diluted by 500 times a substantially lower dose than that given to non-human primates, which didnt show ill effects.

In a press conference on 5th April, TeGenero said that this incident challenges all of us in the biotechnology industry to think again about the safest way to develop new medicines in the future.

As a result of these recent cases, Europeans for Medical Progress (EMP) is now calling for an independent and transparent scientific evaluation of the use of animals as surrogate humans in drug safety testing. Over 200 MPs support this call.

In a press release sent Thursday, 6th April, EMP stated, "New human-based safety tests before and during clinical trials (such as microdosing, human tissue tests, human DNA chips and microfluidics) could prevent many of these deaths - and could have averted these two recent calamities. Clearly, an assessment needs to be made of the relative performance of the various methods of safety testing available. Substantial evidence exists that animal tests are inadequate for the task but - incredibly - this has never been systematically investigated. The only responsible course of action is to evaluate animal testing scientifically, in an independent and transparent manner."

Says Science Director of Europeans for Medical Progress, Dr Jarrod Bailey, "Significant numbers of people die in clinical trials because there is often no prior information on safety in humans - only dubious reassurances of safety in animals, which we should know by now mean very little. A comparison of testing methods has to be an urgent priority: people's lives are at stake. The Government must act now to protect the public from another TGN1412 or Vioxx in future."

According to several recent reports, adverse reactions to prescription medicines (all tested for safety on animals) are now the fourth leading cause of death in the western world.

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