The final report on the clinical trial of experimental drug, TGN1412, which left six men hospitalised in March, has concluded that aside from some ‘minor discrepancies’, the study was carried out in accordance with regulations.
The Medicines and Healthcare products Regulatory Agency (MHRA) reiterated its view that the side effects had been caused by ‘an unexpected biological effect’, and that none of the discrepancies noted contributed to the adverse reactions.
As soon as the report had been issued, however, lawyers representing the men dismissed the MHRA report as a ‘whitewash’. They are unhappy that the MHRA conducted the investigation, having been the agency that gave the trial the go-ahead in the first place, and want an independent enquiry into the case. They also claim that the MHRA has failed to fully investigate whether the side effects could have been predicted from animal studies.
A probe into the conduct of clinical trials is already underway, overseen by Gordon Duff, professor of molecular medicine at Sheffield University, bit this will look at the design and monitoring of studies, particularly those for biologics with novel mechanisms of action, and will not deliver any specific verdict on the TGN1412 trial.
Among the deviations from good clinical practice (GCP) noted by the MHRA were that the clinical research organisation conducting the study, Parexel, had no formal system to provide 24-hour medical cover and failed to keep appropriate medical records on one patient. It also said it was not satisfied that a doctor employed to screen the volunteers ‘had adequate training and experience for their role’.
Parexel also neglected to ensure that the company which developed the drug, TeGenero, had a robust insurance policy to protect volunteers in case of adverse reactions, according to the MHRA.
But despite the criticisms of Parexel, Professor Kent Woods, MHRA chief executive, emphasised that “the adverse incidents which occurred were not as a result of any errors made in the manufacture of TGN1412, its formulation, dilution or administration to trial participants.”
This view was echoed by BioIndustry Association chief executive Aisling Burnand, who said: “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.”
But Michael Day of Leigh Day & Co, the firm representing two of the volunteers, insisted yesterday that “there are a number of important questions that need answering about what happened with this trial and [the] report by the MHRA answers virtually none of them.”
Day said his clients wanted to know whether cynomolgous monkeys were an appropriate animal model to test TGN14122, whether TeGenero had tested the antibody on human blood, and receive an explanation as to why Parexel did not leave a longer gap between doses which could have limited the number of men exposed to the drug.
He also pointed to allegations that the appropriate treatment for the severe side effects experienced by the men in the study, corticosteroid therapy, was not given for several hours after the side effects emerged.