B Cell Therapies in MS: Entering a New Age in MS Care

A novel approach to targeted immunotherapy, started nearly 2 decades ago, is now bearing fruit.  The role of antibodies in the pathology of the MS plaque has been a hot area of basic research.  Up until recently, MS was thought to be fundamentally a disease driven by the abnormal regulation of a type of immune cell called the T cell. 

An imbalance of subtypes of T cells was considered a core issue to MS plaque development, as shown in animal model of MS.  However, over time it was shown that T cells alone could not recreate an MS plaque experimentally.  As animal models of MS improved over time, it became clear that immune cells other than just T cells were playing a critical role in the development of the MS plaque.  From this research emerged a wealth of new information about the role of the B cell, producer of antibodies, in this process.

The B cell evolves from specific bone marrow stem cells, expressing different types of protein markers on their surfaces at different stages in their development.  In the final stage of maturation, some of the cells become “plasma” cells.  These cells normally play an important role in producing antibodies directed against invading bacteria or viruses.  However, in MS, it appears that some plasma cells have been programmed to target proteins within the myelin sheath coating nerve fibers in the central nervous system.  Thus, both T and B cells appear to work together to attack and degrade myelin.

 In late 2015, exciting results from advanced stage human trials of one such therapeutic, ocrelizumab, were reported.  In the OPERA I and OPERA II studies for relapsing remitting MS, ocrelizumab  was compared against interferon beta 1a (Rebif) in a head-to-head design, enrolling 1656 people with relapsing forms of MS (i.e. relapsing remitting MS and secondary-progressive MS with recent relapses).  In both studies, ocrelizumab significantly reduced the annualized relapse rate (ARR) – the primary endpoint of both studies – by nearly 50 percent compared with interferon beta-1a (Rebif) over the two-year period.  Additionally, ocrelizumab significantly delayed confirmed disability progression by approximately 40 percent compared with interferon beta-1a.  On MRI outcomes, Ocrelizumab  significantly reduced active/inflammatory MS plaque by  90 percent and enlarging MS plaque by around 80 percent compared with interferon beta-1a treated subjects.  Overall, ocrelizumab was well tolerated.

A third study large study evaluated ocrelizumab  for the treatment of primary progressive MS (ORATORIO study.)  This study showed that the drug reduced the progression of neurological disability by about 25% compared to placebo, reduced the total volume of MRI identified MS lesions by 3.4 percent over 120 weeks (whereas the placebo treated group actually increased their MRI lesion load volume by 7.4%), and reduced the rate of whole brain volume loss over 120 weeks by 17.5 percent compared to placebo (p=0.0206). Again, this study showed that ocrelizumab was well tolerated.

As a result of these findings, the FDA has granted “breakthrough therapy” status to ocrelizumab for treating primary progressive MS.  This will allow for a faster review and possible approval.  The maker of ocrelizumab, Genentech, will be submitting the results from all 3 studies to the FDA in the first half of 2016, making it the first B-cell depleter class medication to come to market, and thus broadening  the choice of therapeutics for relapsing forms of MS, and for the first time,  effective therapy for those with primary progressive MS.

While B cell treatments are not yet approved for use in MS, your physicians at the EvergreenHealth MS Center are available to discuss all current and future treatment options, as well as potential opportunities to participate in MS research.