Alemtuzumab (Campath) - factsheet

Date of issue: March 2010

1. Introduction

Alemtuzumab is an experimental new drug treatment that is currently being tested in clinical trials for people with relapsing remitting MS. Although alemtuzumab is not currently licensed for use in MS, it is licensed for use in B-cell chronic lymphocytic leukaemia, a type of cancer.

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2. How alemtuzumab works

Alemtuzumab (Campath) is a humanised monoclonal antibody. Antibodies are proteins produced by the immune system to fight foreign substances, such as infections. Monoclonal antibodies can be produced in large quantities in cell culture in a laboratory. They can be designed to bind to proteins on the body's normal cells, altering the immune response.

Alemtuzumab acts by killing T-cells which form part of the immune system; in MS they mistakenly attack myelin and cause the inflammation seen on MRI scans. It is thought that the T-cells that regenerate following treatment with alemtuzumab will not include those that destroy myelin.

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3. Current research

The first clinical trials of alemtuzumab tested the treatment in both relapsing remitting and secondary progressive MS. In people with relapsing remitting MS, alemtuzumab was shown to reduce the numbers of relapses experienced and improved disability levels immediately. Improvement in disability continued to be seen for up to three years after treatment. However, more mixed results were seen in the 25 people with secondary progressive MS. Although MRI scans over a seven year period showed no new lesions had formed in the brain and spinal cords of those participants who were treated with alemtuzumab, they still continued to accrue disability. This led researchers to hypothesise that something other than the effect of inflammation on myelin is at work in progressive MS[1]. Subsequent trials have looked at whether alemtuzumab works best if used in the early stages of relapsing remitting MS.

Results from a phase II trial^ were published in the New England Journal of Medicine in October 2008[2]. This study enrolled 334 people with active, early relapsing remitting MS, and compared two different doses of alemtuzumab to a high dose of beta interferon 1a (one of the currently licensed treatments for relapsing remitting MS). Participants were randomised to receive either: high-dose alemtuzumab, low-dose alemtuzumab, or beta interferon 1a.

Alemtuzumab was administered via a course of yearly infusions: at the first treatment it was given daily for five consecutive days, then 12 months later it was given once every day for three days. A third course of three infusions were planned after a further 12 months, but not all participants received a third course due to safety concerns (see below). Beta interferon 1a was self-administered three times a week by sub-cutaneous (under the skin) injection. Everyone on the trial received intravenous steroids (methylprednisolone) for three days every twelve months.

The results showed that people receiving either dose of alemtuzumab performed significantly better when comparing the number of relapses experienced over the course of the trial. At three years, 77% of low-dose alemtuzumab and 84% of high-dose alemtuzumab recipients had experienced no relapses compared with 52% of people receiving beta interferon 1a[2].

The results also showed that compared with beta interferon 1a, alemtuzumab reduced the risk of sustained disability by 71%. Although some people on the trial only received two courses of the drug rather than the three planned at the start of the trial, results from the full trial could still be collated as enough patients had received the full three courses of alemtuzumab.

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4. Side effects and contraindications

A low blood platelet count was seen in 3% of the trial participants. Although potentially serious, this is treatable if caught early enough. However, the use of alemtuzumab in the phase II trial was voluntarily suspended in September 2004 following a fatal case of immune thrombocytopenic purpura (ITP) in one of the participants. ITP is a blood clotting disorder caused by low numbers of platelets in the blood, symptoms include purple bruises on the skin and in the mouth, but it can also cause internal bleeding. Following the fatality, strategies were put in place to ensure that all future cases of ITP were recognised early. However, ITP remains a significant risk.

22.6% of the trial participants developed thyroid-related side effects, some more serious than others. These are treatable but can mean lifelong thyroid medication is required.

Flu-like symptoms after infusion were also reported. As alemtuzumab works by suppressing the immune system, anyone on treatment will be more vulnerable to infections such as colds and viruses for some time after the infusion.

The published results of the phase II research discussed the issues associated with treating people in the early stages of MS, "Although our study suggests that alemtuzumab is more effective than interferon beta 1a when given at the earliest stages of relapsing remitting multiple sclerosis, our findings raise the difficult issue of exposing young adults who have little disability to a drug having potentially serious adverse effects. Our trial was not powered to assess the long-term safety of alemtuzumab, nor was it powered to detect uncommon adverse events."[2]

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5. Further information

A phase III trial (CARE-MS1) comparing the lower dose of alemtuzumab used in the phase II study with beta interferon 1a over a two year period was initiated in the UK and the USA in 2007. Trial centres in the UK are: Cambridge, Cardiff, Sheffield, and the Royal London Hospital. This trial is fully recruited and is expected to report in 2011[3].

A second study (CARE-MS2) is comparing alemtuzumab with beta interferon 1a in people who have continued to experience relapses whilst on one of the licensed disease modifying therapies (Avonex, Betaferon, Copaxone or Rebif). In the UK the trial centres are in Bristol, Cambridge, Salford, Sheffield, and the Royal London Hospital. This trial is also fully recruited and is expected to report in 2012[4].

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6. 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.
abstract
Coles AJ, et al.
Alemtuzumab v interferon beta-1a in early multiple sclerosis.
New England Journal of Medicine 2008;359:1786-1801.
abstract
CARE-MS1 ClinicalTrials.gov website: http://clinicaltrials.gov/show/NCT00530348
CARE-MS2 ClinicalTrials.gov website: http://clinicaltrials.gov/show/NCT00548405

^ Note - Drug trials

Phase I studies primarily assess the safety of a drug or procedure. They usually involve a small number of healthy volunteers (10-100) all of whom are given the same treatment.

Once a medical intervention has been proven safe, phase II trials test its effectiveness and whether it has the potential to be of benefit. These trials are larger, typically involving 100-300 people with the condition for which the intervention has been developed - in this case MS.

If the phase II study shows the treatment to be beneficial, phase III studies are conducted to gain a definitive understanding of the effectiveness, benefits and potential side effects in a large group of people (300-3,000) with the condition to be treated. Interventions have to successfully complete a phase III trial before they can be considered for a licence by regulatory authorities.