In another showcase of UK bioscience success, adapted from our Celebrate report which was launched in June, today’s blog tells the story of Lemtrada and its role in the treatment of Multiple Sclerosis (MS).
Lemtrada (alemtuzumab), previously known as CAMPATH, is a humanised monoclonal antibody whose target is CD52, a protein found on mature lymphocytes (a type of immune system cell). It was originally developed for use with bone marrow and solid organ transplantation and in leukaemia and is still used, under the CAMPATH name, for these conditions. However, it has a new role under the name Lemtrada, as a treatment for multiple sclerosis (MS), which was approved in May 2014 by the National Institute for Health and Care Excellence (NICE). Clinical trials, published in The Lancet in 2012, revealed that Lemtrada is making a real impact in the treatment of this difficult and disabling condition.
These publications, and ongoing research, are the culmination of many years of effort by scientists in the UK and elsewhere. Indeed, according to the co-discoverer of the CAMPATH family of antibodies, Geoff Hale, over 2,000 people (from researchers and clinicians to patent lawyers) have been involved in the development of this important treatment. He also acknowledges the invaluable contribution of the patients who took part in early clinical trials of what was, at the time, a very experimental drug.
From the lab to the clinic
The origins of CAMPATH-1 lay in the need for a treatment for graft-versus-host disease (GvHD), a complication of bone marrow transplantation. In 1979, Herman Waldman and Geoff Hale at the Department of Pathology at Cambridge University, funded by the MRC, isolated monoclonal antibodies from rats, which could eliminate donor T lymphocyte (“T”) cells from bone marrow prior to transplantation. It is the attack of these donor T cells on the recipient that causes GvHD. One of these antibodies, CAMPATH-1M, gave virtually complete elimination of the T cells and was selected for further development. The Cambridge lab then came up with another antibody, called CAMPATH-1G, which gave good results in two leukaemia patients and pointed the way to a new direction in this research – the need for a humanised version of the CAMPATH antibody.
As it happened, Michael Neuberger and Greg Winter at the MRC Laboratory of Molecular Biology (just over the road from the pathology labs in Cambridge) were working on producing fully humanised monoclonal antibodies as an important step up from the rat or mouse versions. The two teams worked together to develop humanised CAMPATH (CAMPATH-1H). In 1990, the Therapeutic Antibody Centre (TAC) was set up to take care of large scale production of the CAMPATH antibody.
Shortly after the TAC opened, Waldman and Hale were approached about a young woman with a rare autoimmune disease, with a view to trying CAMPATH-1H, as no other treatment had worked for her. After just a short course of the antibody, the patient responded with complete remission. This was the start of the development of CAMPATH-1H for other autoimmune diseases, including rheumatoid arthritis and, later, multiple sclerosis.
Lemtrada in Multiple Sclerosis
In 1991, Alastair Compston’s group at the Department of Neurology in Cambridge was contacted about CAMPATH-1H by a middle-aged patient with MS. She went, within a few months, from being confined to a wheelchair to being able to ski. Magnetic resonance imaging (MRI) scans showed a reduction in the inflammation that is one of the hallmarks of MS. The researchers began a pilot trial and, by 1998, 29 patients had been treated with CAMPATH-1H.
Further research followed, culminating in two Phase III trials and in 2014 NICE recommended Lemtrada as treatment for relapsing-remitting MS. The antibody is given by infusion once a year, for five days in the first year and three days in the second. For the patient, this compares favourably with other treatments, which involve oral tablets or weekly injections. Recently, Genzyme announced magnetic resonance imaging data that show that Lemtrada is associated with a slowing of brain atrophy (loss of neurons and connections) in MS.
30 years on from its beginnings in the lab, Lemtrada’s benefits for patients continue to grow.
Like to find out more? The full version of the Lemtrada story, along with five other case studies, can be found in our report, “Celebrating UK bioscience: unravelling the stories behind UK bioscience success”.