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Alemtuzumab (Campath) - factsheet

Date of issue: October 2008

Introduction

Alemtuzumab is an experimental new drug treatment for people with relapsing/remitting MS. Results from clinical trials to date have been promising so the MS Trust has devised a factsheet to summarise the information currently available. Alemtuzumab is already licensed for use in B-cell chronic lymphocytic leukaemia, a type of cancer.

What is alemtuzumab?

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 and which in MS mistakenly attack myelin and cause the inflammation seen on MRI scans. It is thought that the T-cells regenerated following treatment with alemtuzumab will not include those that destroy myelin

Alemtuzumab is not currently licensed for use in MS and clinical trials are ongoing.

Clinical trials to date

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] Consequently, they have looked at whether alemtuzumab works best if used early in relapsing/remitting forms of 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 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.

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. Beta interferon 1a is an under-the-skin injection that is self-administered three times a week. Everyone on the trial received intravenous steroids (methyprednisolone) for three days every twelve months.

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]

It is worth noting that many people receiving alemtuzumab only received two courses of the drug (at the start and at twelve months) due to safety concerns. Results from the full trial could be collated as enough patients had received their full dose of alemtuzumab by this time.

Safety concerns and side effects

Low blood platelet count was seen in 3% of the trial participants. Although potentially serious, this is treatable if caught early enough. The use of alemtuzumab in this clinical trial was voluntarily suspended in September 2004 following one fatal case of immune thrombocytopenic purpura (ITP), a blood clotting disorder. Following the fatality strategies were put in place to ensure that all future cases were recognised early. However, it remains a significant risk.

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

Flu-like symptoms after infusion were 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 this research discusses the issues of treating people at a very early stage 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]

Phase III trials

A Phase III trial (CAMMS 323) comparing the lower dose of alemtuzumab used in the Phase II study with beta interferon 1a over a two year period started in the UK and the USA in 2007. The UK trial centres are Bristol, Cambridge, Cardiff, Plymouth and the Royal London Hospital. The study is expected to report in 2011.[3]

Amongst other criteria, participants must:

  • have relapsing/remitting MS with at least two attacks in the last two years, and at least one relapse in the last twelve months
  • have experienced first MS symptoms (regardless of diagnosis) within the past five years
  • have an EDSS score of 3 or less
  • not have taken any disease modifying drug before starting on this clinical trial
  • be willing to avoid pregnancy or conception for the length of the trial

A second study will compare 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 will take place in Cambridge and at the Royal London Hospital. This study is expected to report in 2012.[4]

Amongst other criteria, participants must:

  • have relapsing/remitting MS with at least two attacks in the last two years, and at least one relapse in the last twelve months
  • have experienced first MS symptoms (regardless of diagnosis) within the past ten years
  • have an EDSS score 5 or less

References

  1. 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.
  2. Coles AJ, et al.
    Alemtuzumab ve interferon beta-1a in early multiple sclerosis.
    New England Journal of Medicine 2008;359:1786-1801.
  3. Current Controlled Trials website
  4. Current Controlled Trials website

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.