The MHRA’s interim report on the TGN1412 came out this week. In some places it was reported as a tightening up of clinical investigations, in other areas, rather predictably to my mind, it has been attacked as a whitewash. Here’s Paul Flynn MP:
Paul Flynn MP (Newport West) said the report on the dangerous reaction to the drug’s trial is a predictable whitewash. It was an act of lamentable lack of care to give a drug, never before ingested by human beings, to six people virtually simultaneously.
The MHRA is wholly funded by the pharmaceutical industry and its membership comprises many with pharmaceutical interest as employees and shareholders. We now know that the MHRA failed to consult on a similar “monoclonal antibody†which had caused severe toxic reactions in patients.
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We need a comprehensive, rigorous, genuinely independent inquiry. We cannot allow the regulators to investigate the regulators Paul Flynn said the Medicines and Healthcare Products Regulatory Agency (MHRA) has a poor record in failing to detect the severe adverse side effect of both Vioxx and Seroxat. The side effects of 144,000 heart attacks and strokes as result of taking Vioxx were detected in the United States. Our ramshackle MHRA system detected only a handful of adverse effects.
Paul Flynn’s criticisms fit in with his existing views on the pharmaceutical industry and the MHRA. His initial criticism of the TGN1412 trial was extremely ill-informed, accusing US companies of trying to muscle in with an unneccessary treatment for period pains and headaches – strange, given the two drug companies involved were German and the diseases they hoped the drug would be used in were leukaemia and rheumatoid arthritis.
Another accusation comes from a lawyer, Ann Alexander, who is representing the men harmed by the TGN1412 trial [See also the Telegraph]:
the solicitor representing the two most seriously affected victims of the Northwick Park drugs trial, today condemned the report of the regulatory body investigating the aborted clinical trial as “totally inadequate”. She called for an independent Inquiry into the conduct of the trial and said that she would be making her concerns about the MHRA known to the Secretary of state for Health. She said she would also be notifying the Parliamentary Select Committee on Health whose report published exactly a year today found “serious weaknesses” in the MHRA.
“The MHRA’s report gives no detailed information about the pre-clinical trials, about which there has been conflicting information since the trial was suspended”, says Ms Alexander. “How long did it last, what animals were involved, what were the effects, and had these trials been completed? My clients and the general public are entitled to answers to these questions”
“The MHRA has also failed to publish the trial protocol which provides detailed information on how the trial should have been conducted. The Lancet has already condemned the drugs companies for not releasing this information. This omission has now been compounded by a regulatory authority which is supposed to be acting in the public interest and has manifestly failed to do so” said Ms Alexander.”
Again, you will note the attempt to widen the discussion away from the decision to allow the TGN1412 trial into a more generalised concern about the MHRA’s performance. Note that Ann Alexander’s firm also represented families who believed their children were damaged by MMR vaccine. Their website says of MMR: “It has always seemed to us that the vital question that needed answering was whether or not MMR causes autism. That question remains unanswered.” Oh, dear.
Drugresearcher.com carries some comment from the MHRA about the accusation that a trial from last May, of another drug, should have forewarned them of potential problems with TGN1412:
Also provoking criticism are clinical trial results, available since last May, about another monoclonal antibody, for metastatic renal cancer, claiming to go through the same immune response pathway.
Toxicities from that drug, which included enteritis, hypophysitis and meningitis, were observed in 12 of 20 volunteers, of whom one patient underwent a colectomy for perforation.
TGN1412 binds to a molecule called CD28 that is present on the cell surface of T lymphocytes, cells which the renal cancer drug also targets, albeit at a different receptor – CTLA4.
“The trial referred to in the US involved the use of a different drug acting on a different receptor at a different stage in the drug’s development,” MHRA spokeswoman Sara Coakley told DrugResearcher.com.
“It is not clear why this trial would be predictive for outcomes with a first in-man trial with TGN 1412.”
In an article arguing for better communication and greater transparency in The Independent, Professor Ragnar Lofstedt is concerned about risk aversion by regulators:
there is a need for more involvement by independent experts in the regulatory process. If this does not happen, regulatory bodies will continue to lose public trust. And if this occurs, these same regulators, as we have seen in the past, will become more risk averse in order to regain credibility. Thereby they may deny patients life-saving treatments.
Both The Observer and The Independent also carry the news that the drug firm knew of the risk and that the MHRA was warned of the possible effect. Neither of these stories seems particularly damning, especially given that the warning was about a different drug, and the absence of an effect in animal testing. In fact, it would have been more damning if the reports stated that the drug company had not told the MHRA about the potential risk.
Professor Kent Woods, chief executive of the MHRA, denied that risks had been ignored. He said: “The possibility of a cytokine storm was specifically considered and tested for in a particular species of monkey which showed no toxic reaction. With a 500-fold dilution the protocol for the study was as precautionary as you could get.”
If people are trying to suggest the MHRA have learnt nothing from the TGN1412 trial, then I think they are wrong. The fact that all similar trials of biologicals will now require external expert review, is clear evidence that they have learnt something – and this is only an interim report. I personally think the term Whitewash is being thrown about for reasons only tangentially connected with the TGN1412 trial. The Expert Group set-up by the Secretary of State for Health also seems clear evidence of a willingness to learn from this incident, and to prevent future occurrences.
So do you think it was a whitewash? Comments, anonymous or not, are welcome below.