Novel therapies in development: 4 reports


REPORT FROM ECTRIMS – BARCELONA, SPAIN – OCTOBER 7-10, 2015 – A number of novel therapies that target inflammation and/or neurodegeneration in MS are currently being investigated. Among them is MEDI-551, a B-cell directed monoclonal antibody that depletes CD19+ B cells. Unlike CD20+ (targeted by ocrelizumab and ofatumumab), CD19+ is expressed throughout B cell maturation, from pro-B cells to early plasma cell stages.

Phase I results for MEDI-551 in MS are now available (Agius et al. ECTRIMS 2015; abstract P528).  A total of 28 subjects were randomized to placebo or one of five doses of MEDI-551: 60 mg or 300 mg SC on day 1; or two doses (days 1 and 15) of 30, 100 or 600 mg IV. Higher doses were associated with more prolonged B cell depletion. The number of new/enlarging T2 lesions at day 169 was 0.4 with MEDI-551 versus 2.2 with placebo. The most common adverse events were fever, nasopharyngitis, oral herpes and increased blood pressure. Infusion/injection reactions occurred in 40% of patients receiving the IV formulation, and 33% receiving subcutaneous drug. Two patients administered MEDI-551 experienced serious adverse effects (fever, accidental opioid overdose, death). The death was not attributed to the study drug. A second trial in neuromyelitis optica (N-MOmentum) is currently recruiting.

The ACCLAIM phase II trial examined abatacept (Orencia), a T cell costimulation modulator used to treat rheumatoid arthritis (Khoury et al. ECTRIMS 2015; abstract P573). No significant differences were seen with abatacept versus placebo with respect to clinical or MRI endpoints.

Preclinical results are available for two novel remyelinating agents. ABT-555 is an antibody that targets Repulsive Guidance Molecule-a, which inhibits remyelination and axonal regeneration (Mueller et al. ECTRIMS 2015; abstract P582). ABT-555 was associated with increased remyelination and axonal regeneration in the spinal cord and optic nerve models of EAE. Further studies in healthy controls and in MS are ongoing.

Sobetirome (GC-1) is a thyromimetic agent that has been investigated as a lipid-lowering agent due to its effects on hepatic LDL receptors and bile acid production (Tancevski et al. Recent Pat Cardiovasc Drug Discov 2011;6:16-19). It also has potential application in MS since it mimics triiodothyronine (T3), which has been shown to promote oligodendrocyte differentiation from oligodendrocyte precursor cells in EAE (Franco et al. Exp Neurol 2008;212:458-467). A preliminary study in mice found that the volume of demyelination was significantly lower following daily injections of sobetirome or T3 (Bourdette et al. ECTRIMS 2015; abstract P583), suggesting that thyromimetics may merit further study in EAE and MS.

Reviewer: Dr. Daniel Selchen, Head of Neurology, St. Michael’s Hospital, Toronto, Canada

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