Parenteral drugs for MS: What's ahead
EXPERT ANALYSIS FROM THE CMSC/ACTRIMS ANNUAL MEETING
"The data with ocrelizumab looks great. I think, personally, it could potentially replace natalizumab, depending upon the safety," Dr. Coyle said.
Development of ocrelizumab as a treatment for rheumatoid arthritis and lupus was discontinued because of concerns about an increase in opportunistic infections.
"We’ve not really seen that in the MS cohort so far. It’s a slight background concern. So far, ocrelizumab seems pretty safe," according to the neurologist.
Daclizumab (Zenapax): This subcutaneously administered agent is a humanized IgG1 monoclonal antibody against CD25 and is already on the market for the prevention of organ transplant rejection. It is in the ongoing DECIDE study, a phase III MS clinical trial with intramuscular interferon beta-1a as the comparator. Earlier studies raised some concerns regarding safety and tolerability.
A particularly interesting feature of daclizumab is that it appears to have a biomarker predictive of efficacy: an increase in CD56 bright natural killer cells. Biomarkers of efficacy are desperately needed for MS therapies.
Miscellaneous parenterals: These include other anti-CD20 monoclonal antibodies, among them ofatumumab (Arzerra), already marketed for treatment of refractory chronic lymphocytic leukemia; secukinumab, an anti-interleukin-17 monoclonal antibody that showed efficacy in terms of MRI lesions in a small study; an anti-LINGO-1 monoclonal antibody aimed at stimulating myelin repair; and stem cell therapies that are early in development.
Dr. Coyle predicted more efficacy biomarkers are coming, and noted that neuroprotection and CNS restoration are areas wide open for drug development. Her final prediction regarding parenteral therapies for MS: "A high-efficacy monoclonal antibody, if it’s safe and convenient, could seize the market. The safety will be the critical issue."
She reported having received honoraria from Acorda, Accordant, Bayer, Biogen Idec, EMD Serono, Genzyme/Sanofi Aventis, Novartis, Roche, and Tera.
