Alemtuzumab (Campath, Lemtrada)
- Overview
- How does it work?
- How is it given?
- What are the results so far?
- Side effects
- What further studies are planned?
- References
Overview
| Drug in development |  |
|---|---|
| Alemtuzumab |  |
| Other names | Campath, Lemtrada |
| What is it for? | Relapsing remitting multiple sclerosis (MS) |
- Alemtuzumab is an experimental drug treatment for relapsing remitting multiple sclerosis. It is given as an intravenous (iv) infusion for 3-5 days annually.
- Alemtuzumab acts by killing T-cells, a type of lymphocyte involved in the MS immune response.
- In phase III studies, alemtuzumab reduced relapses by approximately 50% compared to beta interferon 1a (Rebif). Some studies have found that disability progression has been halted, and in some cases reversed.
- Two significant side effects have occured:
- idiopathic thrombocytopenic purpura (ITP), a disorder that prevents blood from clotting, was fatal in one case
- overactive thyroid gland (Graves disease) or abnormal thyroid function, affecting 1 in 5 people.
- The manufacturer has submitted alemtuzumab for licensing in Europe. A decision is expected in 2013. NICE has begun preliminary work on the appraisal with a decision expected in April 2014.
How does it work?
Alemtuzumab binds to an antigen called CD52 which is found on the surface of certain T-cells, a type of lymphocyte involved in the MS immune response, and kills the T-cell.
This monoclonal antibody was licensed to treat a type of leukaemia (under the brandname MabCampath).
How is it given?
Alemtuzumab is given by intravenous infusion. In clinical trials, alemtuzumab was given as an iv infusion for 5 days and again for 3 days one year later.
What are the results so far?
The early clinical trials of alemtuzumab were run in both relapsing and progressive types of MS.
In people with relapsing remitting MS, alemtuzumab reduced the numbers of relapses that people experienced and improved their disability levels immediately. Improvement in disability continued for up to three years after treatment.
However, more mixed results were seen in a study of 25 people with secondary progressive MS. MRI scans over seven years showed no new lesions forming in the brains and spinal cords of those participants who had been treated with alemtuzumab, but the people on this trial continued to accrue disability. This led researchers to the idea that something other than inflammation of myelin is at work in progressive MS. Subsequently, research has been directed at treating relapsing remitting MS.
- Results from a Phase II trial (CAMMS 223) were published in the New England Journal of Medicine in October 2008.
This study enrolled 334 people with active, early relapsing remitting MS, and compared two doses of alemtuzumab with a high dose of beta interferon 1a (Rebif).
The results showed that people receiving both doses of alemtuzumab performed significantly better comparing the number of relapses at the end of the trial. At three years, 77% of low-dose alemtuzumab and 84% of high-dose alemtuzumab receivers had experienced no relapses, compared with 52% of people receiving beta interferon 1a. The results also show that compared with beta interferon 1a, alemtuzumab reduced the risk of sustained disability by 71%. - Participants in the CAMS 223 trial have continued to be monitored and data from the Year 4 follow-up were presented at the 62nd annual meeting of the American Academy of Neurology April 2010. The data indicated that around 71% of people treated with alemtuzumab remained free of disease activity up to three years after their last course of treatment. Furthermore, around 91% of people receiving alemtuzumab showed no worsening of their disability compared to 68% of people taking Rebif [P04.213].
- Five-year follow up data from this study was presented at the 63rd Annual Meeting of the American Academy of Neurology April 2011. It showed that 65% of those receiving alemtuzumab remained free of clinically active disease (defined as both relapse-free and with no sustained increase in disability as measured by the Expanded Disability Status Scale) up to four years after their last course of treatment, compared to 27% of patients receiving beta interferon 1a3. However, people on either drug whose MS had worsened in the first few years were excluded from the follow-up studies [PD6.003].
Results of two larger phase III studies were published in 2012.
Comparison of alemtuzumab and Rebif efficacy in multiple sclerosis, study one (CARE-MS I) - CAMMS 323
This phase III trial compared alemtuzumab with interferon beta 1a (Rebif) in 581 people with relapsing remitting MS who had not previously taken a disease modifying treatment. Alemtuzumab reduced relapses by 55% compared to interferon beta 1a over the two years of the trial. 78% of the alemtuzumab group were relapse-free during the trial compared with 59% of the interferon group. The effect on disease progression was similar, with 8% of the alemtuzumab group and 11% of interferon beta group showing a worsening in EDSS measure of disability.Comparison of alemtuzumab and Rebif efficacy in multiple sclerosis, study two (CARE-MS II) - CAMMS 324
This second phase III trial compared alemtuzumab with interferon beta 1a (Rebif) in 657 people who had experienced at least one relapse whilst taking a disease modifying therapy. Over the course of the two year study, alemtuzumab reduced relapse rates by 49% compared to interferon beta 1a. 65% of the alemtuzumab group were relapse-free during the trial compared with 47% of the interferon group. 13% of the alemtuzumab group showed sustained accumulation of disability compared with 20% of the interferon group. For those taking alemtuzumab this was equivalent to a 42% reduction in risk of worsening disability measured by EDSS, compared to the interferon group.
Side effects
Two significant side effects have occurred during alemtuzumab treatment:
- idiopathic thrombocytopenic purpura (ITP), a disorder that prevents blood from clotting, was fatal in one case, has affected 1-3% of participants
- overactive thyroid gland (Graves disease) or abnormal thyroid function, affecting 15-20% of participants (approximately 1 in 5 participants)
Other common side effects seen in the clinical trials have been:
- infusion-related reactions such as headache, rash, fever, nausea and urticaria, affecting 90% of participants in the two large phase III studies
- infections such as coughs, colds, chest infections and herpes virus (mostly skin) affecting 67-77% of participants in the phase III studies
What further studies are planned?
Comparison of Campath and Rebif Treatment on Cognition in Multiple Sclerosis (MS)
A subset of the participants in CAMMS 324 will receive further testing designed to investigate how well alemtuzumab and Rebif work in treating MS-related cognitive problems (e.g., attention, memory, speed of thinking).
Estimated completion date late 2011.
Further details of this study.Extension studies
Three year extension studies of the phase II and III studies will examine long-term safety and efficacy of alemtuzumab and determine if and when further alemtuzumab treatment is needed, and the safety and efficacy of this "as needed" treatment.
Further details of this study.
References
Coles AJ, et al.
The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy.
Journal of Neurology 2006;253(1):98-108.
Read abstract
Coles AJ, et al.
Alemtuzumab vs interferon beta-1a in early multiple sclerosis.
New England Journal of Medicine 2008;359:1786-1801.
Read abstract
Khan O et al.
[P04.213] Alemtuzumab reduces disease progression in RRMS: long-term results of the CAMMS223 trial.
American Academy of Neurology 62nd Annual Meeting; 2010 April 10-17; Toronto, Canada.
Twyman C
[PD6.003] More Alemtuzumab Relapsing-Remitting Multiple Sclerosis Patients Are Free of Clinical Disease Activity at Five Years.
American Academy of Neurology 63rd Annual Meeting; 2011 April 9-16; Hawaii, USA.
Cohen JA, et al.
Alemtuzumab versus interferon beta 1a as first-line treatment for patients with relapsing-remitting multiple sclerosis: a randomised controlled phase 3 trial.
Lancet 2012 1 Nov [Epub ahead of print].
Read abstract
Cole AJ, et al.
Alemtuzumab for patients with relapsing multiple sclerosis after disease-modifying therapy: a randomised controlled phase 3 trial.
Lancet 2012 1 Nov [Epub ahead of print].
Read abstract