What constitutes a cure?
What else needs to be done going forward? Dr. Hauser called for the MS field to develop a definition of cure. “We should take the lead from cancer therapeutics, where they define what a cure means.” In B-cell leukemia, for example, patients are considered cured “if they remain completely disease-free in terms of clinical symptoms and biomarkers of clonal proliferation for 4 years. They have less than a 1% lifetime risk of relapse. They’re essentially cured. Our equivalent could also be developed for MS.”
He highlighted the IMPACT MS phase 4 trial, a small single-center study of ocrelizumab, which just finished enrollment and will examine the effect of the drug on treatment-naive patients at the moment of their first-ever attack. The primary endpoint is oligoclonal bands in 3 years. “I think more of these studies will probably follow,” Dr. Hauser said.
Is intervention possible at the presymptomatic stage? Targets could be members of families with multiple affected relatives who test positive for the predictive antibody signature and who have a high genetic score, he said. “We could do perhaps an Epstein-Barr virus intervention trial in this population. Then, if we have the courage and are more confident in our biomarkers, perhaps even a therapeutic trial, as has been done in these other diseases.”
As for next-generation therapies, “we’ll need to neutralize multiple cell types, especially in later disease,” he said. Bruton tyrosine kinase inhibitors “seem to be a class of drugs that was designed for the MS patient because they not only hit B cells, but also the plasmablasts that CD20s don’t hit and are the main component of the humoral pathology in chronic MS lesions.”
Dr. Hauser discloses scientific board (Accure, Alector, Annexon), board of directors (Neurona), consulting (BD, Moderna, NGM Bio), and travel reimbursement/writing support (Roche and Novartis).