Tested on monkeys and lab animals
No reaction noted
Side effects in human volunteers: Life threatening complications, immune system, lungs, kidneys begin to fail, cytokine release syndrome results in near death
Unpredicted reaction to drug by human body to blame

The violent adverse reactions on six healthy volunteers who took the new monoclonal antibody TGN1412 in a clinical trial conducted by TeGenero, recently, occurred due to an unpredicted biological action of the drug, according to an interim report from the UK Medicines and Healthcare Products Regulatory Agency (MHRA).

TeGenero's TGN1412 was designed to treat autoimmune disease like rheumatoid arthritis and multiple sclerosis and a form of blood cancer.

Experts said the latest report may fuel the growing controversy that biologics are different from chemical-based classic pharmaceuticals. And that it’s time to think about a suitable way to evaluate biologics, to avoid similar horrendous side effects in the future.

"If these findings were to be confirmed, it would indicate that this product showed a pharmacological effect in man which was not seen in pre-clinical tests in animals at much higher doses,'' MHRA’s chief executive professor Kent Woods said about the TeGenero mishap.

TeGenero mishap: Manufacturing, dosing or protocol not to blame

The report thus pre-empted the possibility to put blame on the manufacturing process, problems in dosing or study protocol.

Six healthy volunteers participated in the phase I trial of TGN1412 experienced life-threatening side effects grouped under the title 'Cytokine Release Syndrome,' on March 13. All the volunteers had received TGN1412 drug; two volunteers given placebo did not experience similar side effects.

Following this, the MHRA suspended the TGN1412 trial, and set in place a programme of investigations that probed whether problems in dosage, formulation, contamination, or other aspects of protocol or manufacturing had taken place. The report found no evidence of any such occurrence.

Five of the six volunteers who particpated in the TeGenero TGN1412 clinical trial have since been released from the hospital.

TeGenero, the company that sponsored the drug TGN1412, said that pre-clinical animal tests did not show any deaths related to the drug, and only one animal had to be euthanized after an unrelated bacterial infection. Parexel International ran the trial.

However, the BioIndustry Association (BIA), the UK biotechnology trade association, said the MHRA decision to investigate trials of monoclonal antibodies in general may be 'broader than it needs to be.' The problem with the TGN1412 trial was not the monoclonal antibody, Best argued, but its target, CD28, a regulator of the immune system. Even if the drug had been a classic pharmaceutical, the result would likely have been the same.

TeGenero AG, responding to the report of the MHRA’s findings said in a statement that the preliminary findings of the TGN1412 investigation underline that Tegenero observed the highest standards in developing this drug and that these symptoms were both unexpected and unforeseeable. The information released shows that there was no sign of risk from the pre-clinical tests of TGN1412.

The animal study results of TeGenero's TGN1412 show that there were no drug related deaths in the tests with just one animal sadly having to be put down during the trial after suffering severe diarrhoea caused by an unrelated bacterial infection.

TeGenero mishap; Northwick Park Hospital confirms discharge of two volunteers

Meanwhile, Northwick Park Hospital confirmed that two of the volunteers in the trial of TGN1412 have been discharged from hospital having responded well to treatment. They will continue to visit the hospital for check ups.

Three other volunteers have left Critical Care and are making a good recovery, although they continue to receive specialist care and observation. One volunteer in the drug trial remains in a critical condition but is continuing to respond to treatment. TeGenero remains in close contact with the doctors treating the volunteers to provide all possible assistance to them.

The tested substance TGN1412 is a new treatment for the devastating illnesses of leukaemia, rheumatoid arthritis and multiple sclerosis.

TeGenero said about the TGN1412 trial, "We are shocked about the symptoms we have seen in the volunteers. Extensive pre-clinical tests showed no sign of any risk. We observed strict standards for this clinical test and we obtained all required approvals both in Germany and Great Britain. TGN1412 drug was tested extensively in laboratories and has been tested on rabbits and monkeys. We saw no drug related adverse events and there were no drug related deaths."

Parexel was conducting the first human testing of TGN1412 for TeGenero AG. The trial was approved by the MHRA and the local ethics committee. There is no further human testing of TGN1412 being pursued.

TeGenero AG

Located in Würzburg, Germany, TeGenero AG is a privately held biopharmaceutical company dedicated to the development of innovative therapeutic drugs for the treatment of severe immunological disorders.