Long-term compensation may be in sight for the healthy volunteers whose exposure last year to the experimental monoclonal antibody TGN1412 put them in intensive care.

The two UK law firms acting for the volunteers made a breakthrough this week when they met with lawyers representing the insurers of Parexel, the US-based contract research organisation that conducted the TGN1412 study on behalf of Germany’s TeGenero and has refused to accept liability for its disastrous outcome.

Leigh Day & Co, which represents four of the men who suffered extreme adverse reactions to TGN1412 in the Phase I trial at London’s Northwick Park Hospital, said it would now attempt to “hammer out a framework to enable our clients to obtain suitable compensation”. According to Gene Matthews, one of the lawyers handling the case, a framework agreement on compensation should hopefully be in place by the end of this month, after which discussions can move on to individual cases.

Irwin Mitchell, which is acting for the two men most seriously injured in the TGN1412 study, was also at Tuesday’s meeting with the lawyers for Parexel’s insurers and is working closely with Leigh Day & Co in the push for compensation, Matthews noted.

The case changed complexion after Leigh Day & Co was instructed to start legal proceedings against Parexel for negligence in its handling of the TGN1412 trial. As the law firm pointed out, a year had passed since the incident without the CRO offering any compensation to the volunteers. The four men represented by Leigh Day & Co had accepted interim payments of £10,000 each from TeGenero but the German company, which had taken out insurance cover of just £2 million for the first-in-man study, subsequently filed for bankruptcy.

Parexel has stood its ground since a report on the trial by the UK’s Medicines and Healthcare products Regulatory Agency (MHRA) last May criticised the company for some minor deviations from Good Clinical Practice (GCP) but concluded that the severe adverse reactions were not a result of “any error made in the manufacture of TGN1412, its formulation, dilution or administration to trial participants”. As the CRO noted, the full value of TeGenero’s £2 million cover was still available to settle compensation claims. However, the stakes have risen with fears that the volunteers could go on to develop life-threatening conditions such as autoimmune diseases or cancer.

The magnitude of this risk is what the UK lawyers are now trying to pin down. If the risk is strong, Matthews explained, the hope is that an agreement can be reached on damages over and above the £2 million available, with the possibility of the volunteers coming back for further compensation if their condition deteriorates. The settlement could stretch to millions of pounds, or “hundreds of thousands” even without taking any long-term health consequences into account, he said.

According to Matthews, the crux of the negligence claim against Parexel was the way the company’s medical staff dealt with the adverse events. Despite indications in the trial dossier that the cytokine storm induced by TGN1412 was a “real possibility”, the volunteers did not receive high-dose steroids to counter the reaction until they were in the care of the NHS, he pointed out. Leigh Day & Co has also raised questions about the extent of Parexel’s involvement in the trial design, particularly the dosing of TGN1412 at 5-8 minute intervals when expert advice was to leave at least a few hours between doses.

These concerns were echoed in a new report on the Northwick Park incident by the Royal Statistical Society. A working party convened by the Society made 21 recommendations for improving the conduct of first-in-man studies, concluding that the design of the TGN1412 trial was “not well suited to its objectives of testing safety and tolerability of the drug”.