Pharma Strategy Blog

Commentary on Pharma & Biotech Oncology / Hematology New Product Development

This post is an update to an earlier one I posted 2 years ago relating to the sad events of TGN1412. Someone sent me an email asking what had happened to the volunteers in the clinical trial at Northwick Park in London.

T helper cell function

Image via Wikipedia

Let's recap.  TGN1412 was an experimental drug being investigated for the treatment of multiple sclerosis,
leukemia and arthritis.  It was a monoclonal antibody that stimulated
the
immune system's T-cells.  Tests on animals showed the drug to be 'safe'.

However, in a fated phase I trial in humans, the men who received
doses
of TGN1412 suffered a massive inflammatory response (Cytokine Release
Syndrome), and within 12 hours were admitted to hospital with multiple
organ failure. The two patients receiving placebo were unaffected. TGN1412 was manufactured by the now insolvent German
biotech company TeGenero.  Parexel, a contract research organisation,
ran and administered the trials on behalf of the company.

The final investigation into the disastrous trial presented 22 recommendations to the UK Health Secretary, the main one
being that an advisory body to assess high-risk clinical studies should
be established. It also recommended that volunteers who are ill, as
opposed to healthy candidates, should be considered for some drug
trials.  This is standard practice in trials involving cancer drugs, but not immunology.

It is still unclear why was the drug tested on healthy volunteers rather than immune compromised patients.  Phase I trials in healthy volunteers raise special ethical issues when the benefits are non-existent and the risks are high.  This was important in this trial, in which an agonist targeted at compromised immune systems was given to individuals with intact immune systems. 
The cytokine storm that followed is hardly surprising from a basic biochemistry standpoint.

The TGN1412 trial, which nearly killed six male volunteers, took
place at London's Northwick Park Hospital in March 2006.  One
victim's head swelled up like the "elephant man" and another has had
fingers and toes amputated.  All six victims have been told their risk
of contracting diseases due to impaired immune systems has gone up;
this includes cancer and multiple sclerosis.

In addition to government action the pharmaceutical industry has
revised its guidelines on clinical trial management and local and
national bodies have agreed to improve communications.

The leader of the independent inquiry, Professor Duff, said he was confident the new
recommendations, if adopted, would greatly reduce the likelihood of
another disaster and ensure that the well being of volunteers is put
first.

An editorial in the BMJ summed things up:

"Finally, what does this trial tell us about the degree of transparency throughout the process of developing new drugs? Many groups have called for mandatory registration and disclosure of clinical trials and their protocols.  Had this trial been available for public review, potential problems might have been identified and avoided.  Despite claims of the need to protect competitive advantage, public interest overwhelmingly requires that all information about this drug and this trial should now be made publicly available immediately. Lives are at stake and there can be no possible reason, save liability, for secrecy. 

We have been assured repeatedly that proper procedures were followed, when the real question is whether they were the right procedures."

Sources:

BMJ


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One Response to “What happened with TGN 1412 two years on?”

  1. Paul

    This so-called “clinical trial” was obviously done on healthy subjects because it was not actually a clinical trial. It was the endgame testing of a bioweapon that was developed by the United States and other criminal Western governments. This is why the story has practically fallen off the planet Earth and has gone completely unreported in the mainstream press in the last three years. Now with the recent orchestration of the so-called “swine flu pandemic” and references to “cytokine storms” being thrown around in the mainstream press (New York Times)I think
    the World is about to be reintroduced to this bioengineered material as it is used by the criminals to motivate the further destruction of the US Constitution and hasten the arrival of a dictorial world government.

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