April 5, 2006

scientists react to latest findings from MHRA on suspended clinical trial

The MHRA released its interim report into the adverse incidents which occurred at Northwick Park Hospital on 13 March 2006 during the clinical trials of TGN1412. The report said that the trial showed no obvious errors, nor could the adverse effects have been predicted.

Dr Sophie Petit-Zeman, Director of Public Dialogue, Association of Medical Research Charities (AMRC), said:

“The responsibilities of researchers and doctors running drug trials must be unambiguously to those who volunteer to be involved, whether they are healthy subjects or patients, and we hope the secretary of state’s expert working group will underline this. It is right to be thoroughly investigating this case, while keeping in mind the previously good track record of clinical trials as the essential bridge between rigorous animal studies and the use of new treatments.”

Aisling Burnand, Chief Executive of the BioIndustry Association (BIA), said:

“The BIA urges continued swift action by the MHRA to put the new measures in place and introduce any further appropriate measures. As a joint initiative, the BIA and the ABPI propose setting up an expert working group to provide industry input to this process. We have also offered to nominate industry experts to work in partnership with the MHRA to assist in their ongoing activities relating to this issue.”

David Webb, Professor of Clinical Pharmacology, University of Edinburgh, said:

“This report suggests, by elimination of other possibilities, that the serious adverse effects suffered by the healthy subjects in the TGN1412 study were an unpredicted effect of the drug at the dose given, and not a problem with dosing or manufacture. This does raise questions about the development of monoclonal antibodies and drugs targeting the immune system and there may need to be changes in the design of first in man studies in this area to minimise these risks. One obvious difference might be to dose subjects sequentially rather than at the same time, which at the very least would minimise the number of subjects put at risk.”

Dr David Ehrenstein, Reader in Rheumatology/Consultant Rheumatologist, Department of Medicine, UCL, said:

“This announcement means that the effects were not due to contamination but as a direct result of activating T cells through CD28 resulting perhaps in cytokine release (there is a faint possibility that CD28 might be on another cell type in humans but not in mice/primates). It is also likely that signalling through CD28 is different between human and mouse.”

Dr David Chiswell, founder and ex-CEO Cambridge Antibody Technology (CAT), said:

“This is an interim report that nothing untoward has happened in the mechanics of the trial or the manufacturing process of the drug. It remains to be seen whether a full understanding of the biological effects of the antibody in all of the species tested would help prevent this sort of terrible reaction happening again.”

Dr Simon Festing, Executive Director, Research Defense Society (RDS), said:

“Animal testing is like wearing a seat-belt. It can prevent many problems, but is no guarantee of safety. We are all concerned that these severe effects apparently did not show up either in human tissue tests or animal tests. Further research will be essential.”