Alemtuzumab (Campath, Lemtrada)
Other names Campath, Lemtrada
What is it for? Relapsing remitting multiple sclerosis (MS)
What stage is it at? Phase III
How does it work?
This monoclonal antibody is currently licensed to treat a type of leukaemia (under the brandname MabCampath). 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.
How is it given?
Alemtuzumab is given by iv infusion. In recent clinical trials, alemtuzumab was given by a course of infusions once a year; for five consecutive days at start of treatment, once every day for three days after one year of treatment, and for some people, once every day for three days after two years of treatment.
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 improving 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 1. 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 2.
- 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] 3.
- 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] 4.
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, which is one of the currently licensed treatments for this type of MS. People were randomised to receive either high-dose alemtuzumab, or low-dose alemtuzumab, or 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% 2.
What studies are underway or planned?
Comparison of alemtuzumab and Rebif efficacy in multiple sclerosis, study one (CARE-MS I) - CAMMS 323
Comparison of alemtuzumab and Rebif efficacy in multiple sclerosis, study two (CARE-MS II) - CAMMS 324
Comparison of Campath and Rebif Treatment on Cognition in Multiple Sclerosis (MS)
Extension studies
This phase III trial comparing the lower dose of alemtuzumab used in the phase II study with beta interferon 1a (Rebif) in 581 people over a two year period started in the UK and the USA in 2007.
Results expected Q3 2011.
Further details of this study.
This second phase III trial is comparing two doses of alemtuzumab with beta interferon 1a (Rebif) for two years in 840 people who have continued to have relapses whilst on one of the licensed disease modifying therapies.
Results expected Q4 2011.
Further details of this study.
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.
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.
Side effects and contraindications
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
- overactive thyroid gland (Graves disease) or abnormal thyroid function
Additional safety measures are being taken to allow early diagnosis and treatment of these side effects.
Latest update on licensing status
In June 2010, alemtuzumab was granted Fast Track status by US Food and Drug Administration (FDA) 5. The FDA's Fast Track program is designed to expedite the review of new drugs that are intended to treat serious or life-threatening conditions and demonstrate the potential to address unmet medical needs. Under Fast Track designation, alemtuzumab for MS is eligible for Priority Review and the FDA may consider for review portions of the marketing application before the submission of a New Drug Application (NDA) is completed.The FDA decision will not affect the drug's European licensing.
References
- Coles AJ, Cox A, LePage E et al.
The window of therapeutic opportunity in multiple sclerosis: evidence from monoclonal antibody therapy.
Journal of Neurology 2006; 253(1): 98-108. - Coles AJ, et al.
Alemtuzumab vs interferon beta-1a in early multiple sclerosis.
New England Journal of Medicine 2008;359:1786-1801. - 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. - Genzyme press release.
Genzyme's alemtuzumab for treatment of multiple sclerosis granted fast track status by FDA
Date: 14 June 2010 [cited 2010: June 24]
Available from Genzyme website