New results for two novel therapies
Promising new results have now been published for two monoclonal antibody (MAb) drugs in development that may provide additional options over the next few years. MAbs are biological agents that target highly specific targets. MAbs currently used in MS are Tysabri (natalizumab) and Lemtrada (alemtuzumab).
Ofatumumab (Arzerra) was originally developed to treat a form of leukemia (see Novel multiple sclerosis treatment reports first results. MSology, January 30, 2014). It selectively targets one type of immune cells called B cells, which contribute to MS inflammation in the brain and spinal cord. (Another drug, ocrelizumab, works in a similar way and is also in development for MS.)
Like other MAbs, ofatumumab is administered by a slow drip (infusion) into the vein. In the phase II study, 38 people received two drug infusions two weeks apart or placebo infusions (Sorensen et al. Neurology 2014;82:573-581). Among those completing the six-month study, inflammatory lesions seen on MRI were reduced by over 99%. Infusion reactions were common at first but were less frequent with the second dose. Thus far, there have been concerns about the possibility that treatment may reactivate viral infections (such as hepatitis). Some cases of progressive multifocal leukoencephalopathy (PML) have also occurred when higher doses of ofatumumab were used to treat leukemia, so this may become an issue in MS as well. Additional studies will need to determine the effectiveness and safety of the drug over a longer time period.
The second study was a follow-up of the phase II SELECT study of daclizumab. This MAb blocks the activation of immune cells and was originally developed (as Zenapax) to prevent tissue rejection in people receiving an organ transplant. In the original SELECT trial, monthly subcutaneous injections of daclizumab (either 150 mg or 300 mg) resulted in a 50% reduction in relapses compared to a placebo after one year of treatment (Gold et al. Lancet 2013;381:2167-2175). About 80% of people had no relapses, compared to 64% on the placebo.
For the extension phase of the study, those in the daclizumab groups continued on therapy for another year and people in the placebo group were switched over to active treatment (Giovannoni et al. Lancet Neurol 2014;13:472-481). The main objective was to evaluate safety. About 6-8% of people developed serious side effects. These serious effects were slightly more common in people on treatment for the full two years. There were two deaths: one due to abscess in the first year of treatment, and one due to autoimmune hepatitis in the second year. So the safety profile of the drug will need to be evaluated carefully in larger phase III studies.
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