The U.S. Food and Drug Administration (FDA) has approved LemtradaTM (alemtuzumab) for the treatment of patients with relapsing forms of multiple sclerosis (MS), Sanofi and its subsidiary Genzyme announced today.
“Today’s approval is the culmination of more than a decade of work by Genzyme to develop Lemtrada,” said Genzyme President and CEO, David Meeker.
Lemtrada, began life as Campath-1H, a drug developed out of research by Professor Herman Waldmann and colleagues in the Department of Pathology at the University of Cambridge which began in 1979. However, the story of Campath stretches back to research by Dr César Milstein at Cambridge’s MRC Laboratory of Molecular Biology in 1975 to develop monoclonal antibodies – artificially-produced antibodies, a key component of the immune system which rids the body of invading organisms; this work was to win César Milstein and George Köhler the Nobel Prize for Physiology or Medicine in 1984. Cambridge Enterprise played a key stewardship role over the long commercial development of the MS drug.
Today’s approval is the culmination of more than a decade of work by Genzyme to develop Lemtrada.David Meeker
Campath-1H was originally developed as an immunosuppressant to prevent the rejection of bone marrow transplants. The original versions of the drug – Campath-1M and Campath-1G – were developed using mouse and rat antibodies; it would take the development of ‘humanised’ monoclonal antibodies – which replace regions of the animal antibody with human equivalents – for the drug to be successful in humans. This new drug, Campath-1H, was successful at treating two types of blood cancer, lymphocytic leukaemia and non-Hodgkin lymphoma.
Campath-1H was identified as a potential treatment for multiple sclerosis by Professor Alastair Compston, Professor of Neurology and Head of the Department of Clinical Neurosciences, in the late 1980s. Multiple sclerosis is an autoimmune disease in which the immune system begins to attack the body’s own healthy nerve cells, stripping away their protective myelin sheath and preventing electrical signals from passing smoothly and quickly between the brain and body. The drug 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 regards myelin and nerves as foreign.
The first MS patient was treated with the drug in 1991 and as evidence began to mount that the drug would be effective, if used to treat people before the disease process had progressed too far, Professor Compston and his colleague Dr Alasdair Coles, who joined the team a few years later, expanded the trials. Eventually, the results of phase III clinical studies, published in 2012, confirmed that the drug is effective both in MS patients who are previously untreated (‘first-line’ therapy) and those who have already failed another treatment.
The FDA approval of Lemtrada is based on two pivotal randomized Phase III open-label rater-blinded studies comparing treatment with Lemtrada to Rebif® (high-dose subcutaneous interferon beta-1a) in patients with relapsing remitting MS who were either new to treatment (CARE-MS I) or who had relapsed while on prior therapy (CARE-MS II).
In CARE-MS I, Lemtrada was significantly more effective than interferon beta-1a at reducing annualized relapse rates; the difference observed in slowing disability progression did not reach statistical significance. In CARE-MS II, Lemtrada was significantly more effective than interferon beta-1a at reducing annualized relapse rates, and accumulation of disability was significantly slowed in patients given Lemtrada vs. interferon beta-1a. The clinical development program for Lemtrada involved nearly 1,500 patients with more than 6,400 patient-years of safety follow-up.
“The unmet need in MS remains high,” said Edward Fox, M.D., Ph.D., Director of the Multiple Sclerosis Clinic of Central Texas. “It is a great day for people living with relapsing forms of MS in the United States, who will now have access to this new meaningful treatment.”
First approved in September 2013 in the European Union, Lemtrada is approved in more than 40 countries. Additional marketing applications for Lemtrada are under review by regulatory agencies around the world.
Multiple sclerosis is estimated to affect more than 2.3 million people globally.Tags: autoimmune, campath, david meeker, genzyme, herman waldmann, lemtrada, leukaemia, lymphoma, multiple sclerosis, pathology