Ocrelizumab (OCREVUS™), an anti-B cell therapy has been approved by the FDA as of March 28th 2017, for the treatment of Relapsing-remitting multiple sclerosis (RRMS) and primary progressive multiple sclerosis (PPMS). This treatment is highly effective for RRMS, based on the data from the Phase III clinical studies. It is also the first drug approved for use in PPMS. At IMSMP/TISCH we have used Rituximab, a similar anti-B cell treatment, for the past 16 years with great success. It is because of the effectiveness of this therapy (Rituximab) we were able to persuade Medicare to cover the costs of this therapy in New York.
Rituximab, however, is NOT approved by the FDA for use in MS. At our center we use it as an off-label drug. This unfortunately can require several weeks to obtain approval from insurance carriers and often approval may be denied.
Therefore, the approval by the FDA of Ocrelizumab, which should have almost identical anti-B cell activity to Rituximab, appears to be good news for MS patients. However, there are some serious concerns with Ocrelizumab that patients need to be made aware before they consider this therapy. First, in the RRMS trial, there were 9 patients who developed various malignancies within three years of taking Ocrelizumab (4 patients within the first 2 years and 5 patients in the following year). This is alarmingly high considering that these patients were mostly in their third decade of life and had no previous history of cancer. In the trial for PPMS patients, 13 patients developed cancer within the three years of taking Ocrelizumab (11 in the first two years and 2 additional cases in the following year). This means that more than 1 in 50 patients developed cancer within three years of taking Ocrelizumab among the PPMS patients. These risks of malignancy associated with Ocrelizumab are not seen with Rituximab (more than a thousand patients just at our center since 2001 and several hundred thousand worldwide). This risk of cancer with Ocrelizumab is not explained at present and the magnitude of the problem cannot be defined, as the medication has not been given for a period longer than 3 years.
There are also additional concerns with Ocrelizumab, such as the risk of life threatening infections which caused the trials in patients with Rheumatoid arthritis and SLE to be halted in 2010.
Although, it is indeed progress that the first medication for PPMS has been approved, the patients should be fully informed of its’ potential risks. For patients who can obtain Rituximab, it would be safer to continue with this therapy, until with time, we are better able to advise patients about the risks associated with Ocrelizumab.