A neuroimmunologic revolution
Historically, the field of neuroimmunology has included diseases such as neuromyelitis optica (NMOSD), which has recently experienced its own revolution. Positive results from phase 3 programs of 3 distinct immune system–targeted therapeutic modalities in development for NMOSD were featured at this year’s meeting. Eculizumab, a terminal complement inhibitor, satralizumab, a monoclonal antibody targeting IL-6, and inebilizumab, a B cell–depleting monoclonal antibody targeting CD19 were all associated with significant reductions in relapse rate; the study designs varied with regard to inclusion criteria (eg, aquaporin-4 [AQP-4] status, background immunomodulatory therapy). These breakthroughs have paved the way for the potential near-term introduction of 3 treatment options for a disease that currently has no available treatments.
In contrast, the already robust MS treatment landscape continues its evolution, with new immune-targeted pipeline agents in development. Two additional CD20-targeted monoclonal antibodies (to the already-approved ocrelizumab [Ocrevus®]) currently in phase 3 development, ofatumumab and ublituximab, were represented in the program. Also presented were positive 48-week data from a phase 2 study in relapsing MS of evobrutinib, a Bruton’s tyrosine kinase inhibitor, which also mediates B-cell receptor signaling. Notably, many of the more recent mechanisms being extended to the MS treatment landscape have their roots in oncology, which is undergoing an immunologic revolution of its own. As in oncology, adoptive cell therapy may not be too far off in the field of neuroimmunology. In fact, results of a phase 1b study of the effects of autologous tolerogenic dendritic cells loaded with myelin and AQP-4 peptides, showed successful elicitation of antigen-specific IL-10 production by T regulatory cells in patients with NMOSD or MS.
Recent discoveries have expanded the neuroimmunologic disease umbrella to include Alzheimer’s disease, PD, and ALS, which have been traditionally regarded as primarily neurodegenerative diseases. Recent research suggests that inappropriate immune responses contribute to PD pathogenesis, underpinning poster presentations at this year’s meeting that reported phase 2 study designs of the tyrosine kinase inhibitors, K0706 (PROSEEK) and nilotinib (Tasigna®; NILO-PD), the latter of which is approved in chronic myeloid leukemia. Researchers who undertook preclinical studies of imatinib (Gleevec®) in the G93A-SOD1 mouse, a model of ALS, which has also more recently received attention for its associated immune system alterations, said that the observed effects of delayed age of onset and slowed disease progression, coupled with the ability of the drug to cross the blood-brain barrier, suggest that further exploration of the therapeutic potential is warranted.
The advent of immune checkpoint inhibitors (ICIs) in the era of immuno-oncology had influence over the AAN meeting program. During the meeting, a review from the Mayo Clinic showed a 1.5% risk of neurologic autoimmune side effects with ICI use, potentially greater with combination therapy and retreatment. Overall, there were over 10 oral and poster presentations reporting on such adverse effects included in this year’s meeting program.