Oxford's part in a new multiple sclerosis drug | University of Oxford
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Oxford's part in a new multiple sclerosis drug

Jonathan Wood

A highly effective new treatment for multiple sclerosis was approved yesterday by the European Medicines Agency, the regulator for drugs in Europe.

The drug can offer people with early multiple sclerosis many more years free from worsening disability, and Oxford played an important role in the drug's development.

Professor Herman Waldmann was involved in the early discovery work with the antibody drug at Cambridge University and brought a significant proportion of the research to Oxford when he moved here in 1994.

Once in Oxford, his team worked on the manufacture of the drug, contributed important new understanding of how the drug worked, and investigated the drug's application in a number of disease areas.

Cambridge continued to lead the clinical trials of the new drug in multiple sclerosis, and it is these which have now seen the drug approved by the European regulator.

The newly approved drug is called alemtuzumab and is made by the drug firm Genzyme, which will market the drug under the brand name Lemtrada.

'We are very pleased and proud of this outcome,' said Professor Waldmann. 'In particular, we have great admiration for the neurology team in Cambridge, with whom we have worked on this project for so many years. Their commitment and focus has been exemplary, and this has been a good example of basic and clinical science collaboration at its best.'

Although now approved for use in the EU, it still remains to be determined whether this drug will become a common treatment option for NHS patients, as the drug has not yet been assessed by the National Institute for Health and Care Excellence (NICE) for multiple sclerosis.

Multiple sclerosis affects 2.5 million people worldwide and approximately 100,000 people between the ages of 20-40 years in the UK. The disease sees the patient's own immune system attack their nerve cells, resulting in symptoms including numbness, tingling, blindness and even paralysis. Although some recovery may occur, the majority of patients relapse and then see repeated relapsing and remitting stages. Current treatments require frequent administration and are only moderately effective, reducing the relapse rate by only approximately 30%.

Alemtuzumab has the potential to make a great difference to patients, in terms of a better quality of life and not having to take treatments continuously.

'It is the first drug for multiple sclerosis that only needs to be given for a short course to provide long-term benefit,' explained Professor Waldmann, though the drug does need to be given before the disease has progressed too much.

The drug offers people with multiple sclerosis an improvement in their ability to function in their daily lives, a significant slowdown of disease progression and fewer disease relapses, he says. 'It compares favourably in terms of efficacy to most of the current treatments.'

Alemtuzumab reboots the immune system by first depleting a key class of immune cells, called lymphocytes. The system then repopulates, leading to a modified immune response that no longer attacks myelin and nerves as foreign.

But in doing so, roughly one third of multiple sclerosis patients develop another autoimmune disease after alemtuzumab, mainly targeting the thyroid gland and more rarely other tissues especially blood platelets.

Dr Alasdair Coles of the University of Cambridge explains: 'Alemtuzumab offers people with early multiple sclerosis the likelihood of many years free from worsening disability, at the cost of infrequent treatment courses and regular monitoring for treatable side-effects.'

The Cambridge research team is currently investigating how to identify people who are susceptible to this side-effect and seeing whether this side-effect can be prevented.

It was soon after the Nobel laureates Cesar Milstein and George Kohler invented the technology for making large quantities of monoclonal antibodies at the Laboratory of Molecular Biology that Herman Waldmann and others in Cambridge produced the first monoclonal antibody for potential use as a medicine. This antibody, then called Campath-1H and now known as alemtuzumab, was subsequently licensed for the treatment of chronic lymphocytic leukaemia.

In the 1980s, the scientists also began to explore the drug's use in autoimmune diseases, which occur when the body's immune system mistakenly attacks healthy tissue.

'By applying the drug in leukaemia, vasculitis, bone marrow and organ transplantation, we learned lot about how to use it, and this was the background for the application in multiple sclerosis,' explained Professor Waldmann.

Through the 1990s, while Cambridge neurologists began to explore the use of alemtuzumab as a treatment for multiple sclerosis, the Therapeutic Antibody Centre at the University of Oxford led by Professor Waldmann – a unique facility at the time – permitted the development and manufacture of alemtuzumab for clinical trials.

And through this partnership between Oxford and Cambridge, it was determined how the drug worked and its advantages in multiple sclerosis became clear.

Professor Alastair Compston and Dr Coles of Cambridge University led the subsequent clinical research to develop alemtuzumab in partnership with Genzyme.

Professor Compston said: 'This announcement [by the European Medicines Agency] marks the culmination of more than 20 years' work, with many ups and downs in pursuing the idea that Campath-1H might help people with multiple sclerosis along the way. We have learned much about the disease and, through the courage of patients who agreed to participate in this research, now have a highly effective and durable treatment for people with active multiple sclerosis if treated early in the course.'