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The press release is available from the MHRA website: www.mhra.gov.uk
Professor Karol Sikora, Visiting Professor of Cancer Medicine and honorary Consultant Oncologist at Imperial College School of Medicine, Hammersmith Hospital, said:
“It’s good that the disaster was not caused by contamination of the active agent. It is perhaps surprising that the MHRA have not commented on the wisdom of giving six healthy volunteers a completely novel compound at the same time. If the administration had been staggered, then the scale of the disaster would have been minimised.”
Aisling Burnand, Chief Executive of the BioIndustry Association (BIA), said:
“It is welcome that the expert group chaired by Professor Gordon Duff is looking at the science surrounding monoclonal antibody treatment, and how trials involving these types of drugs need to be managed in the future.
“Clinical trials are tightly regulated in the UK and Phase I trials have a good safety record. It is important to recognise that the events in the TeGenero trial were exceptional.
“Since the first biologic drug, human insulin, was approved in 1982 for diabetes patients, more than 250 million patients worldwide have benefited from approved biotech medicines. Of these, 17 are monoclonal antibodies, helping patients across a variety of indications including cancer, rheumatoid arthritis and transplant rejections.”
Professor Geoff Hale, Professor of Therapeutic Immunology, University of Oxford, said:
“These events are yet another setback for non-commercial clinical trials. Since 2004, the ultimate responsibility for such trials passed from doctors to administrators. They will find it difficult to authorise trials of new agents.”
A spokesperson from the Association of the British Pharmaceutical Industry (ABPI), said:
“A joint taskforce has been set up by the BioIndustry Association (BIA) and the Association of the British Pharmaceutical Industry (ABPI) to provide industry input to the expert working group set up to learn from the TGN1412 clinical trial adverse events at Northwick Park.
“Safety is at the forefront of all that we do, and it is imperative to examine carefully every aspect of the clinical development of ground-breaking medicines that work in a novel way related to that at the centre of this incident.”
Professor Chris Higgins, Director, MRC Clinical Sciences Centre, said:
“It is reassuring that this report found no serious errors by Parexel and the MHRA. This does raise the issue, in retrospect, that when a completely new class of drug is being tested there should be additional burden of proof regarding safety before it is first put into man.”
Francis P Crawley, Director General, Good Clinical Practice Alliance – Europe, said:
“The MHRA Report does not explain why this clinical trial was accepted and performed in the United Kingdom while its earlier submission to the German authorities was still pending further information. This was a German scientific project performed in the United Kingdom. This project needs to be understood in relation to national and European Union laws and practices governing clinical trials.
“Competition between the United Kingdom and other European countries for the business interests of these kinds of (Phase I) clinical trials may have contributed to the research being too hastily performed in the United Kingdom. There seems to be some evidence of this in the MHRA Report where it is indicated that the trial took place before key contractual agreements were completed. It is not clear whose interest the MHRA Report serves.
“I do not believe it will satisfy the public’s well-founded interest to know why the lives of six people were endangered. The MHRA should, not only investigate this single clinical trial, but it should also review its policies and practices regarding the ethical review and government oversight of these kinds of (Phase I) clinical trials.”
Dr Sheena McCormack, Senior Clinical Scientist, MRC Clinical Trials Unit, said:
“The testing of new drugs in clinical trials is an essential part of assessing their benefits and risks with the goal of developing new treatments which can save or prolong life or improve the quality of life. However no clinical research is without some risk to those taking part, as the TeGenero trial clearly demonstrates.
“The MHRA has thoroughly investigated the facilities involved in this ‘first in man’ trial and some of the possible explanations for the devastating consequences can now be ruled out. The drug was given in correct dose and there is no evidence of manufacturing errors or to date of contamination.
“This trial raises new and complex scientific issues and the formation of an expert group to consider the implications for future clinical trials of similar novel products is welcomed. It may be that the guidance that has worked to protect the public thus far in the development of new therapies, needs strengthening for such circumstances.
“As an immediate precaution, MHRA has implemented an additional review of trials of similar products, and the research community is looking carefully at future protocols to ensure that there is a much more cautious approach to dosing in the first individuals to receive them.”
Dr David Glover, an independent consultant and industry expert on the development of antibody and other biological drugs, said:
“Today’s report is inadequate and completely misses the point. The report concluded the problem was due to an unexpected biological effect, but this is absolute nonsense. The trial volunteers’ response was predictable from preceding literature and data supplied by the company and should not have come as a surprise.
“The trial itself should not have been approved because there was no measure for the potency of the product and as a result there was no way to tell if one batch of drug was more potent than another.
“In the absence of a potency test this drug should not have gone into trials at this stage. However, even if you believe it should have gone into man, it should not have gone into healthy volunteers because the mechanism of action is not appropriate in those volunteers. The mechanism of action of the drug is to kick-start a component of the immune system. In healthy volunteers the immune system is working fine and does not need to be kick-started, therefore it would be more appropriate to test in volunteers with a suppressed immune system.
“Given that the drug was expected to be potent, it should have been given at a much lower dose and it shouldn’t have been given so rapidly – it should have been dripped in more slowly. And given that a reaction to the drug could have been predicted, sufficient time should have been left between individuals receiving the drug to allow possible reaction to occur.
“MHRA are not taking responsibility for this disaster and today’s report makes them look complacent and arrogant. There has been a failure of process at MHRA and today’s report shows that they have a box ticking mentality – much more thought should have applied to really fundamental aspects of the drug before approving this trial.
“I am concerned that there will be calls for more guidelines, more regulations, and more safeguards, but to do so will miss the point. It is not more data that is needed it is the right data – scientifically sound and clinically relevant. Assessors at the Regulatory Authority need to be trained in biological drug development and to know when to seek expert help from outside – if both these had been done we would not have had the disaster to deal with.”
Professor Geoff Hale, Chief Executive Office, BioAnaLab Limited, said:
“Improvements can be made to the approval and management of Phase I clinical trials. We already have laboratory tests which could predict the risk of cytokine storm. I doubt whether extending the expert advisory system will be so practical or helpful.”