Posted: 20 February 2017. Updated: 20 February 2017
Over a decade ago, human clinical trials of test drug TGN1412 resulted in catastrophic injury to test volunteers. The story is the subject of a BBC drama documentary ‘The Drug Trial: Emergency at the Hospital’ and the National Anti-Vivisection Society (NAVS), which funds advanced non-animal techniques, has pointed to the dangerously misleading results from animal testing.
According to the manufacturer, TeGenero, the drug had been tested extensively in laboratory animals including rabbits, dogs and monkeys with no drug-related adverse events.
The drug was given to healthy volunteers in doses 500 times weaker than that given to lab monkeys, but in an hour the volunteers were so seriously ill that they had to be transferred to intensive care at London’s Northwick Park Hospital.
In the clinical trial the volunteers suffered multiple organ failure caused by a massive immune reaction, as the drug triggered an uncontrollable response from antibodies. The worst affected volunteer was hospitalised for three months. They appear to have suffered permanent damage to their immune systems, and one has had fingers and toes amputated. The impacts of the drug mean the men live with the danger of developing cancer, lupus and rheumatoid arthritis.
The side effects experienced included soaring body temperatures, dilated blood vessels; plasma leaking into surrounding tissue and dramatically falling blood pressure. One man’s head and neck were said to have swollen massively and his limbs turned purple. Another was said to resemble the “Elephant Man”.
There are disturbing similarities to the BIA 10-2474 trial tragedy in January 2016, with both trials apparently massively misinformed by animal testing data leading to human tragedy and death.
The BIA 10-2474 trial was conducted by the French research company Biotrial on behalf of Portuguese pharmaceutical company Bial. Six male volunteers in the highest dose group received the drug by mouth; after three days one was admitted to hospital after feeling sick and died a week later. The other five men were also hospitalised, with four displaying neurological symptoms and at least one losing all his fingers and toes.
An investigation and report confirmed that high doses had been administered over long periods to four different animal species – monkeys, dogs, mice and rats – with no comparable effect. Doses in some monkeys are estimated to have been around 75 times higher without causing neurological toxicity like that seen in humans.
The fundamental flaw of animal-based research is that each species responds differently to substances, making animal tests an unreliable predictor of potential human effects. Studies have shown that, due to the biochemical changes resulting from stress in the laboratory, test results can be affected by the animal’s age, diet, sex, even its bedding material and results from the same tests on the same species can vary from laboratory to laboratory. For example, morphine drugs are a depressant in rats, dogs, hamsters and other species, but produce tremors and convulsions at comparable doses in mice and cats; penicillin is a useful antibiotic for people but it kills guinea pigs; cancer drug 6-azauridine can be used in humans for long periods, but in dogs small doses produce potentially lethal results in a few days; heart drug Eraldin was thoroughly studied in animals and satisfied the regulatory authorities. None of the animal tests warned of the serious side effects in people, such as blindness, growths, stomach troubles, and joint pains.
Increasingly, more predictive advanced technology is at the forefront of development and safety testing of medicines.
Accelerator mass spectrometry (AMS) is an analytical tool of unprecedented sensitivity. It can be used to study samples from human volunteers given ultra-low, harmless, doses of new drugs (called micro-dosing).
Obtaining early metabolism data from the relevant species (humans) can avoid the unnecessary exposure of volunteers in Phase 1 clinical trials to potentially toxic drug candidates.
Following TGN1412 it was widely reported that micro-dosing may have avoided the horrific consequences.
Today there is a wealth of modern sophisticated techniques that can study the human condition. In addition to micro-dosing and spectrometry analysis, there is computer modelling, a range of scanning techniques, cell and tissue culture.
It is vital that governments and regulators drive research towards these modern techniques that benefit people instead of insisting on the chaos of animal tests.
‘The Drug Trial: Emergency at the Hospital’ will be broadcast on BBC2 at 9pm on Tuesday 21 February.