Multiple Sclerosis patients have significant and sustained reduction in disability and risk of relapse on Alemtuzumab versus Rebif®.
Edinburgh; UK 23rd October 2008 – Results recently published in the 23rd October issue of the New England Journal of Medicine (N Engl J Med 2008;359:1786-1801) showed very promising results from a clinical trial with a drug called alemtuzumab (branded Campath), in patients with early-stage relapsing-remitting multiple sclerosis (RRMS). The results are from the final three-year analysis of a Phase II clinical study (CAMMS223) that involved 334 patients, not previously treated for the disease (treatment naïve patients).
The trial showed that when early-stage MS patients received alemtuzumab, their condition improved significantly more than those patients who received beta-interferon – the current standard of care. More specifically, patients with early RRMS taking once-yearly cycles of alemtuzumab reduced their risk of relapse by 74 percent and the risk of sustained accumulation of disability by 71 percent compared to patients treated with the active comparator Rebif® (high-dose interferon beta-1a). Notably, the mean disability of patients on alemtuzumab improved from baseline, whereas the mean disability of those on Rebif worsened, suggesting that alemtuzumab may be able to restore some lost function in many patients.
These results are clearly very exciting, however it is worth stressing that much more work is needed to confirm these findings and for the drug to be approved for use on the NHS. In that regard the manufacturer is currently running two larger phase III clinical trials - CARE MS-1 (Comparison of Alemtuzumab and Rebif Efficacy in Multiple Sclerosis) in 550 treatment-naïve patients and CARE MS-2 in 1200 patients who have relapsed on previous therapy. Should these findings be confirmed then the drug will be submitted to the relevant regulatory authorities for an ‘approval’ decision, which if favourable, should result in alemtuzumab being licensed for use on the NHS. Unfortunately for MS patients this is unlikely to happen before 2013.
It is also worth noting that this trial was performed in patients with early-stage disease who were treatment-naïve and therefore had not received prior therapy. This means that these particular findings are of limited relevance to patients who have already received treatment for MS or who have had MS for some time. Results from the CARE MS-2 trial mentioned above will study the drug’s effectiveness in these patients.
While the efficacy of the drug is unquestioned, some physicians remain concerned over the drugs propensity to cause serious side-effects – particularly an immunological side effect known as thrombocytopenic purpura (ITP). ITP is a disorder characterized by a low platelet count and corresponding increased risk of uncontrolled bleeding. In this phase II trial (CAMMS223) a total of six alemtuzumab-treated patients, and one Rebif-treated patient, developed ITP, one of which was fatal – the other patients were promptly diagnosed and responded well to medical treatment.
As a result of these adverse events a patient monitoring program was instituted in the trial, and there have been no new cases of ITP reported in CAMMS223 in approximately two years. Furthermore physicians have indicated that as the drug has been used widely for the treatment of leukaemia this side-effect is well understood and manageable with close observation and prompt medical therapy. Given the serve and often debilitating consequences of MS some patients may decide that the risk is worth the benefit.
More positively, alemtuzumab benefits from a relatively good dosing regimen. In this particular trial patients received one intravenous dose of the drug every day for five days for the first cycle, and one intravenous dose of drug every day for three days 12 months later for the second cycle of therapy. Some patients received a third cycle of alemtuzumab therapy at month 24. This contrasts favourably with the troublesome dosing regimens of the currently approved drugs such as Rebif (beta-interferon) injected three times a week, or Copaxone (glatiramer acetate) injected once a day.
In summary, this is exciting news. The drug appears to have a very strong effect on the disease and has a favourable once-yearly dosing regimen. It can however cause severe side-effects. The more extensive clinical trials required to confirm these findings are ongoing but approval for use on the NHS is unlikely before 2013.
Report by Mr Simon Smyth, Pharmaceutical Industry Analyst and advisor to Action MS