Trial drug had affected monkey glands
Monday March 20, 2006
The drug that left six men seriously ill after its first tests on humans had caused the glands of two monkeys to swell in previous experiments, the company behind it said today. However, TeGenero said the monkeys' symptoms were completely different to those suffered by the men being treated at Northwick Park hospital, in north-west London.
The company said two of the 20 monkeys used in pre-clinical tests of the TGN1412 drug - designed to treat rheumatoid arthritis, leukaemia and multiple sclerosis - had experienced a "transient increase in size of lymph nodes".
In a statement, it said information that there was a small chance of temporary swelling as the drug worked on the immune system had been included in details submitted to UK regulators. The information was also on the consent form signed by the volunteers before the trial began.
"We are encouraged by the progress being made by the volunteers, but remain deeply concerned for all of them as they continue their treatment," Thomas Hanke, the TeGenero chief scientific officer, said.
"Once again we would like to thank the excellent work by the doctors at Northwick Park hospital. We are continuing to do all we can to ensure that the investigations into what went wrong proceed as quickly as possible."
The condition of four of the men is continuing to improve after almost a week in intensive care, their doctors said yesterday. Three of the four had now been removed from organ support, Ganesh Suntharalingam, the clinical director of intensive care at the hospital, added. However, he said two other patients remained in a critical condition and said it was still too early to comment on their prognosis despite some early signs of improvement.
The six patients who became ill after being injected with the drug last Monday were continuing to receive specialist anti-inflammatory treatment.
They "went down like dominoes", when given the drug, vomiting and screaming in pain, according to a witness who was given a placebo in the tests. The partner of one volunteer said his face had swollen up "like the Elephant Man".
Parexel, the medical research company responsible for the drug trial, insisted it had followed the correct procedures. TeGenero said TGN1412 was a monoclonal antibody stimulating the production of more white blood cells, known as T-lymphocytes.
While immunologists throughout the world know drugs targeting molecules on T-cells should be developed with care, pre-clinical evidence suggested TGN1412 was a safe and important development in this area, the company added.
The trial drug, a biological rather than chemical product, is a genetically engineered "humanised" protein that is part mouse but mostly human. Unlike old chemical entities, monoclonal antibodies are designed to be accepted by the human body, which experts say makes it difficult to determine through animal testing what dose would be toxic to humans.
Almost all monoclonal antibody drugs aim to suppress an immune system reaction, but TGN1412 does the opposite. "It is designed to turn on white blood cells, particularly a sub-set called regulatory cells," Roberto Solari, the chief executive of Medical Research Council Technology, said last week.
Inflammatory reactions in rheumatoid arthritis are caused by too many cells in the immune system being turned on, and the drug is an attempt to turn on other cells with the power to switch off troublemakers.
Dr Solari said it was possible that "instead of switching on the regulators, we have switched on the activators and super-induced the immune system".