BBC: Six taken ill after drug trials (UK)

[Taxloss]

Six men remain in intensive care after being taken ill during a clinical drugs trial in north-west London.

The healthy volunteers were testing an anti-inflammatory drug at a research unit based at Northwick Park Hospital when they suffered a reaction.

Relatives are with the patients, who suffered multiple organ failure. Two men are said to be critically ill.

An investigation has begun at the unit, run by Parexel, which said it followed recommended guidelines in its trial.

More ...

http://news.bbc.co.uk/1/hi/england/london/4807042.stm

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Who'd have thought that testing experimental drugs could be dangerous?

[dipsydoodle]

1. The Constant Gardner

All further trials have now been moved to Kenya - away from
the press.

[SoCalDem]

2. or India..

I saw a documentary a while back where drug companiews were testing drugs in poor communities where medicine is so scarce, that people lined up to get the "miracle drugs".. They also got "free" medical checkups, so they didn;t seem to mind being guinea pigs.. The drug rep, said that they had "very few" adverse reactions, and did admit that sometimes the follow-ups had been disrupted by people "perhaps" moving and not returing to the clinics.. (or maybe they just died , quietly at home)

[muriel_volestrangler]

3. It will be interesting to know what animal testing had been done

Because such a universal reaction (all 6 subjects taking the real drug taken ill) is the kind of thing you've have thought animal testing would have picked up, unless it's some obscure interaction with a human-only protein or similar. This could feed into controversies both about animal testing and cloning to produce human organs, which might be useful for pre-human trials.

[dipsydoodle]

4. Animal testing

The drug was being trialed for use on leukemia patients. I
just did a quick poll using the mouse population in my back
garden [maybe yard to you]. They reckoned  mice don't suffer
from that anyway and I also have no recollection of my vet
mentioning that any other animals do either.

[muriel_volestrangler]

8. Welcome to DU! (a little late, I know)

No, it's garden to me, too. I grew up not far from you, in Stevenage, and had a summer job in Watford once. If you haven't seen the UK DU Forum (I can't remember your username there), come and join us!

What the disease the drug is aimed at (and it's actually 2 - leukemia, and inflammatory diseases such as rheumatoid arthitis, which seems a bizarre combination to me, but I'm no doctor) isn't really relevant - this was the test on healthy subjects for side effects - which have shown up in a major way.

Animals can get leukemia from viruses - and they have developed mice which mimic the most common form of human leukemia.

[Taxloss]

10. As Mu said, welcome to DU.

My father was born in and grew up in Watford - Rickmansworth, to be precise.

[Taxloss]

6. I'm not sure where this leaves the animal testing debate.

Not that the debate will ever be settled, it's too polarising for that.

I suppose it could be spun either way - either that animal testing doesn't work, or that more intensive animal testing should be undertaken on species closer to humans (ie the higher primates, which are precisely the species that most people understandably feel most uncomfortable about being used in research).

At the very least, this research will simply be exported, not stopped. Better to do it here where the safeguards are better and the victims subjects can get the medical aid they may require.

[dipsydoodle]

7. Higher primates

Bushy and Tiny Blur are higher primates but both are sub human. Maybe test on them - don't think there would be too much objection from the animal rights crowd.

[HysteryDiagnosis]

5. Inflammation Syndrome

http://www.stopinflammation.com/table_of_contents.html

The Inflammation Syndrome
The Complete Nutritional Program to Prevent and Reverse Heart Disease, Arthritis, Diabetes, Allergies, and Asthma
By Jack Challem, The Nutrition Reporter™

Table of Contents

Foreword by Ronald E. Hunninghake, M.D., and Hugh D. Riordan, M.D.

Introduction

Part 1 The Inflammation-Disease Connection
Chapter 1 Meet the Inflammation Syndrome
Chapter 2 Your Inflammation Triggers
Chapter 4 Balancing a Diet That's Out of Balance
Chapter 5 Mistreatment: What's Wrong with Anti-Inflammatory Drugs

[yardwork]

9. It sounds like contamination

Side effects rarely cause multiple organ failure. It sounds like the drug was contaminated with bacteria or something else.

[Benbow]

11. Drug not a peptide but targetted at changing the human immune response

From the BBC web site, "Have your say":

One contributor (Wednesday, 15 March, 2006, 14:57 GMT 14:57 UK)writes, "looking at the background presented on the company's site I ask 'is the science sound?' This is not a normal 'drug' as we know them i.e a chemical compound. This is a Monoclonal Antibody therapy specifically targetted at changing the mechanism of human immune response."

Responding to that contributor, another calling himself only James began by saying (Wednesday, 15 March, 2006, 15:11 GMT 15:11 UK )that he is doing "a PhD in immunoregulation and when i saw that CD28 was the target was quite suprised." The following quotes are all, I think, from James:

The drug isn't a peptide, its a humanised antibody that targets CD28. The inflammatory response on this scale would not be possible if it was an allergic reaction as the patients had no prior exposure. The massive inflammation will almost certainly be due to the agonist/stimulating nature of the mAb targeting CD28.

The drug used specifically activates CD28, a molecule needed to activate cells (T cells). As such the mAb will activate T cells, although another signal is required.

T cells are always being stimulated through their T cell receptor by self antigens but not normally to a level sufficient with the second signal to activate them. In this case the anti-CD28 mAb may provide such a strong second signal that the T cells are pan activating, resulting in the strong inflammatory response.Think along the lines of toxic shock syndrome.
Spoken with a few of the seniors here and they are all quite amazed that CD28 was the target.

[Taxloss]

12. The report in the London Evening Standard is grisly.

http://www.thisislondon.co.uk/news/articles/PA_NEWA11681711142362136A000?source=PA%20Feed

...

It was reported that one man's head had swollen up to three times its normal size.

One of the victims was named as student Ryan Flanagan, 21, of Highbury, north London. The Sun newspaper said he was taken to intensive care three hours after taking the tablets.

His family were told he could not breathe and his head and neck had swollen to three times normal size.

...

"His mother got a call to say his head and neck were swelling up and his legs were purple."

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Yuk!

[muriel_volestrangler]

13. Times: "Drug trial ignored guideline on safety"

Professor Sheila Bird, from the Medical Research Council’s Biostatistics Unit at Cambridge, said: “It is very unusual to have a tragedy in one volunteer in a trial like this, far less to have all six involved. Not just one has suffered a catastrophe, but all of them.”

That could have been avoided, she said, if at the start only one of the volunteers had been given the drug.

All were healthy young men who had volunteered for the first human trials of a new arthritus drug, developed in Germany. It works by targeting the immune system and inducing changes that, it was hoped, would reduce arthritic symptoms and might later be used to treat cancer. Professor Bird, citing the recommendations made in The Textbook of Pharmaceutical Medicine, a standard work on the subject. suggested that the trial would have been better to test two or three volunteers on day one, before the remaining volunteers were given their dose.

However, Chris Springall of Covance Clinical Research, a company based in Yorkshire that carries out drug trials, said that the practice by which the whole group was given a dose at the same time was normal in the industry. But it was not considered risky because side-effects were so extremely rare.

http://www.timesonline.co.uk/article/0,,2-2088290,00.html

So it's industry practice to cut a corner or two to save a day in the trial. Great.

[Taxloss]

14. "arthritus"?

The Times' sub-editors should be ashamed of themselves!

[fed-up]

15. Kicking this as my sis has MS and was given a trial drug that was later

pulled due to a few deaths...

Found this doing a google:
http://www.in-pharmatechnologist.com/news/ng.asp?id=26995-bi-wins-antibody

BI wins antibody contract

17/11/2003 - A small German start-up company has turned to Boehringer Ingelheim to develop a process for the production of a new monoclonal antibody-based drug for immunological disorders
...

TeGenero's antibody is also known as TGN1412 and is currently in preclinical development. It stimulates the activity of T lymphocytes and could be used, for example, to upgrade a patient's immunological response to cancer. It may also be used in a regulatory way, for instance by switching off T cells involved in autoimmune diseases such as rheumatoid arthritis.

and this
http://www.wuerzburg.de/biomed/english/news/717,5982.html
TeGenero AG receives EU-orphan drug designation for Humanized Agonistic Anti-CD28 Monoclonal Antibody TGN1412 for the treatment of B-CLL - March 10, 2005


TeGenero AG announced today that its Humanized Agonistic Anti-CD28 Monoclonal Antibody TGN1412, which is currently in late-stage preclinical development, has received designation as orphan medicinal product from the European Medicines Agency (EMEA) for the treatment of B-cell Chronic Lymphocytic Leukaemia, B-CLL.

“The designation reflects a high medical need for safe and efficacious new treatment options in B-CLL”, says Dr. Thomas Hanke, Chief Scientific Officer of TeGenero. “Due to its novel mode-of-action, TGN1412 has the potential to provide a significant benefit to patients suffering from B-CLL, as demonstrated in recent pre-clinical studies.”

The EMEA orphan drug designation entitles TeGenero AG to exclusive marketing rights in the EU on TGN1412 for ten years following marketing approval and to protocol assistance by EMEA in order to optimize TeGenero´s drug development strategy in compliance with regulatory requirements.

About designation as orphan medicinal product

“Orphan drugs“ are medicinal products used for rare, life-threatening diseases or chronically debilitating conditions where no other or no sufficient effective treatment exists. Benefits of designation as orphan medicinal product by the EMEA include reduced fees for centralized activities as well as advice on the conduct of clinical trials. An orphan designation is not a marketing authorization, which can only be granted after the quality, safety and efficacy of the product have been demonstrated.

[jbnow]

16. You know the MS drug

has been recommended to be put back on the market.

It cost just $24,000 a year, let's all get some.