The history of alemtuzumab use in multiple sclerosis
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). 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, patient S.H. was the first person with multiple sclerosis (secondary progressive) to be treated with (a single 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. Between 1994-1997, 29 patients with secondary progressive were treated with one cycle of Campath-1H combined with anti-CD4 or corticosteroids. 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 to 2002, 22 patients with relapsing-remitting multiple sclerosis treated using two cycles of Campath-1H (Coles 2006). The data from this study was sufficiently exciting to promote investment in a phase 2 trial, “CAMMS223”, ran from Dec 2002 to Sep 2007. 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). We then embarked on two phase 3 trials: CAREMS1 from Sep 2007 to Apr 2011 and CARE MS2 from Oct 2007 to Sep 2011. In 2009 Genzyme and Bayer (previously Schering AG) agreed that Genzyme would take sole responsibility for further development of Campath-1H. Alasdair Coles and Alastair Compston led the phase 2 and phase 3 trials of alemtuzumab in multiple sclerosis and are the first and senior authors on the trial publications.
Licensing of alemtuzumab
In Feb 2011, Sanofi aquired Genzyme, and led the effort to license alemtuzumab. On September 17th 2013, alemtuzumab was licnesed 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. Controversially, the FDA initially rejected Sanofi’s application for licensing in the US in 2013, but by November 2014, alemtuzumab was also approved by the FDA. On 28 May 2014, NICE Chief Executive, Sir Andrew Dillon said: “We are very pleased to be able to recommend alemtuzumab for adults with relapsing-remitting multiple sclerosis. Evidence has shown that alemtuzumab is more effective and less expensive than current similar treatments for those with severe relapsing-remitting MS. The NICE Committee heard from clinical specialists and patients during the appraisal process who described alemtuzumab as a revolutionary treatment for some people, allowing them to live their lives as they had before their diagnosis.”