As of this week, Ocrevus® (Ocrelizumab) is available for prescription and in pharmacies for the treatment of relapsing-remitting (RMS) and primary progressive Multiple Sclerosis (PPMS). Given the good clinical efficacy data and acceptable safety profile, the drug will play a key role in the immunotherapy of Multiple Sclerosis in the future.
Ocrelizumab has been approved by authorities for the treatment of adult MS patients with relapsing multiple sclerosis with active disease (defined by clinical findings or imaging) – for patients who either show a very active course from the outset (with frequent relapses and many MR lesions) or cannot be adequately controlled with established MS drugs (i.e. continue to show relapses or MR activity). In clinical jargon, such patients are referred to as (highly) active.
This group has benefited in the past from the prescription of the antibody Natalizumab (Tysabri®). However, since Natalizumab is being prescribed more cautiously due to the PML risk, it is a welcome development that Ocrelizumab, an antibody, is available as an alternative for the treatment of (highly) active MS patients. Accordingly, I also assume that JCV-positive Natalizumab patients will be interested in switching to Ocrelizumab.
But also for those patients who are not optimally treated with their current MS drugs, the availability of another alternative for (highly) active patients is of interest. My optimism that Ocrelizumab will be significant in these patients is based mainly on the fact that we have been using the concept of the drug, namely the depletion (destruction) of B cells, for some time in MS therapy as an “experimental” alternative, and for this we use Rituximab. Rituximab is an antibody approved for the treatment of rheumatoid arthritis and also destroys B cells.
We have had very positive experiences with Rituximab in many centres in Germany. In addition, Rituximab has been prescribed very frequently in Sweden in recent years for the treatment of MS, and the now longer-lasting observations from Sweden show that the depletion of B cells represents a potent mechanism of action.
Of course, after approval, one always has to put a bit of a damper on the euphoria, as the special features of a drug often only come into play when it is used widely outside of clinical trials. Therefore, in the coming years, the effects and side effects must be observed critically and carefully. For example, it is not completely ruled out that long-term use of Ocrelizumab could result in a disruption of the production of the body’s own defence substances (antibodies). However, I believe that we will still have enough time in the coming years to investigate how the concept of B-cell depletion can be used most successfully in patients with relapsing MS and what dosages and intervals are necessary for this.
In addition, Ocrelizumab has approval for the treatment of primary chronic progressive MS (PPMS), as it was the first drug to achieve the primary study endpoint in a PPMS study. Therefore, Ocrelizumab has been approved for the treatment of early primary chronic progressive PPMS patients, characterised by disease duration and degree of disability, as well as imaging features typical of inflammatory activity. Translated, this means that preference would be given to treating patients with primary chronic progressive MS who have not been sick for long, can still walk and show signs of active inflammation on MRI.
This subgroup benefited far the most in the study program. Therefore, Ocrevus® is certainly no miracle cure – it will be able to help certain selected patients, but the majority of patients who have been ill for a longer time will not benefit to such an extent that it justifies the effort of immunotherapy.
However, it is very good news that there is now also an approved therapy for PPMS patients – and it is to be hoped that this is just the beginning of more effective therapies for progressive MS.
