Testing Novel Drugs in Animals
Over the past decade or so, around one in nine new drugs made it through phase 1 clinical trials to go on to be eventually approved by European or US regulatory authorities.
In 1991 around 40 per cent of drugs that went into phase 1 trials failed to be developed any further because of unanticipated differences in drug metabolism by laboratory animals and by humans.
Thanks largely to the development of non-animal methods and computer predictions by 2000, this has reduced to around 10 per cent of drugs failing for this reason. However, around 60 per cent of drugs still failed at phase 1 for reasons not seen in animal tests.
What does this mean in terms of animal testing? If we consider that six out of every nine failures are due to safety or efficacy problems that were not anticipated from studies in laboratory animals, it is clear that a large proportion of animal tests are not able to predict whether a drug will be effective and safe in humans. This not only means that potentially millions of animals are wasted each year during preclinical drug development, but also that Phase 1 human volunteers may be inadvertently put at risk.
TGN1412: Novel types of drugs and biotherapeutics
TGN1412 was a potential protein-based treatment for B cell leukemia and/or inflammatory disorders such as rheumatoid arthritis. It was a monoclonal antibody that was engineered to be highly specific for a human immunomodulatory protein called CD28.
As a result of the highly human-specific nature coupled with its complex actions on the human immune system, TGN1412 could not be tested on many of the most commonly used laboratory species, such as rats and mice. Furthermore, while some basic tests were conducted on cells in culture, these were not able to predict the effects within the human body.
TGN1412 has raised the issue of whether animals are suitable for testing very human-specific, novel, biological medicines.
Issues such as the possibility of translating the information from studies on similiar products specific for a laboratory species in assessing the risk to humans were considered. The design of clinical trials was also discussed by several expert groups.
FRAME's work in this area included submissions to the Department of Health for consideration by an expert scientific group led by Sir Gordon Duff and to the European Medicines Agency regarding the design of phase 1 clinical trials and the type of information that should be used to decide whether to proceed with clinical trials.
The most prevalent concern is that, where no other laboratory species seems suitable, primates are likely to be increasingly used for assessing biological medicines. However, as seen in the case of TGN1412, not even these tests can guarantee the safety of clinical trials volunteers.