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The University of Cambridge has made a video on the history of alemtuzumab.

See here.

See: The beginnings of alemtuzumab Early use in progressive MS Treating relapsing-remitting MS Licensing of alemtuzumab The future

The beginnings of Alemtuzumab

Campath-1H (now called alemtuzumab) was originally synthesized by Herman Waldmann at the Department of Pathology in Cambridge University (hence Cam- Path) and Geoff Hale, who has written about the early history of Campath here. A really good resource for the history of Campath is this website. Campath was licensed to Burroughs Wellcome via British Technology Group (BTG). The original intention was to use alemtuzumab to treat leukaemia. But in the 1980s, Martin Lockwood explored its efficacy in vasculitis and autoimmune disease. In 1990, Alastair Compston and Herman Waldmann began discussions over the use of alemtuzumab in multiple sclerosis. Burroughs Wellcome conducted discontinued development because of disappointing results in phase II rheumatoid arthritis trials.

Early use in progressive multiple sclerosis

In 1991 the first patient with multiple sclerosis (secondary progressive) was treated with one cycle of Campath-1H. Between 1992-1993, 6 more patients (5 with secondary progressive, 1 with primary progressive) were treated with one cycle of Campath-1H (Moreau 1994). Between 1994-1997, 29 patients with secondary progressive were treated with one cycle of Campath-1H combined with anti-CD4 or corticosteroids (Coles 1999). The main lesson from this experience was that, in order to maximise the benefit from alemtuzumab, we needed to treat early in the course of relapsing-remitting multiple sclerosis. In 1997 Leukosite licensed rights to Campath-1H from BTG and went into joint venture with ILEX Oncology. In 1999 Millennium purchased Leukosite and co- developed Campath-1H with ILEX Oncology. In 2001, Campath-1H licensed, as MabCampath, for the treatment of CLL

Treating relapsing-remitting multiple sclerosis

From 1999 to2002, 22 patients with relapsing-remitting multiple sclerosis treated using two cycles of Campath-1H (Coles 2006). Dec 2002-Sep 2007: the CAMMS223 trial. In 2004 Genzyme acquired ILEX from Millennium. In June 2005 the death of a patient on the CAMMS223 trial led to suspension of dosing of Campath-1H. From Aug 2005 to 2009, we treated 20 people with Campath-1H and a non- binding variant of Campath-1H called SM3.,designed to reduce immunogenicity. It proved effective (Somerfield 2010). Sep 2007-Apr 2011: the CARE-MS1 trial Oct 2007-Sep 2011: the CARE-MS2 trial In 2009 Genzyme and Bayer (previously Schering AG) agreed that Genzyme would take sole responsibility for further development of Campath-1H. In Feb 2011, Sanofi aquired Genzyme. 1999- March 2011 45 people treated at Cambridge with relapsing-remitting multiple sclerosis, outside of Genzyme-sponsored studies, NOT including 20 on SM3 trial and 22 reported in Coles J Neurol 2006. A summary on the long-term follow-up of these 87 patients is currently being written up.

Licensing of alemtuzumab

On 17 September 2013, alemtuzumab was licensed as a treatment of “adult patients with relapsing remitting multiple sclerosis with active disease defined by clinical or imaging feature” in Europe, including the UK. Licensing followed in Canada, Australia, Brazil and Mexico. On 5 April 2014 NICE, the UK body which determines cost-effectiveness of drugs, approved alemtuzumab for “active relapsing remitting multiple sclerosis” (see here). However, on 30 December 2013, the FDA announced that alemtuzumab should not be approved in the United States (see here), because of concerns around blinding in the phase 3 trials. Public details of the FDA meetings can be found here, (under the November 13th meeting). There was a public and professional protests from US and European neurologists. On 7 April 2014, after discussions with the FDA, Genzyme resubmited its application and dropped its appeal (see here).

The future

The efficacy of alemtuzumab is high, but so too are concerns over its safety profile. We aim to reduce the risks associated with alemtuzumab by identifying those in advance who would be at low risk of autoimmunity after alemtuzumab; and we are conducting a trial in which we test whether boosting the thymus gland reduces autoimmunity after alemtuzumab (see here).
YOUR HEADING TEXT Alasdair Coles, Joanne Jones and Alastair Compston Cambridge Neuroimmunology

History of alemtuzumab