Immunomodulatory agents in early stages of development for treatment of MS

Several promising immunomodulatory drugs are in the early stages of development for the treatment of MS. These drugs use a variety of strategies to inhibit the ability of immune cells to cross the blood-brain barrier and enter the CNS and mount an immune attack.

ATL1102 (sponsor: Isis Pharmaceuticals / Antisense Therapeutics) is an antisense inhibitor (antisense refers to a strand of DNA) that targets a receptor on lymphocytes to keep them from passing into the CNS. ATL1102 has been evaluated for the treatment of MS in a Phase 2a study, in which it significantly decreased the number of brain lesions detected by magnetic resonance imaging (MRI) compared with placebo.

Several new medications share a similar strategy for preventing immune cells from entering the CNS. These drugs are called selective modulators of the sphingosine-1 phosphate (S1P) receptor that work to prevent lymphocytes from migrating to the site of inflammation in the CNS.  The S1P receptor modulator BAF312 (Siponimod) (sponsor: Novartis) has been evaluated for use in MS in a Phase 2b study. The results of this study have not yet been published. However, a Phase 3 study of the medication is currently being planned.

Another S1P receptor modulator ponesimod (R-3477) (sponsor: Actelion) has been evaluated for use in MS in a Phase 2b study. The 24-week randomized, placebo-controlled study compared three doses of ponesimod (10 mg, 20 mg, and 40 mg) with placebo in 464 people with relapsing-remitting MS (RRMS). Different doses of ponesimod resulted in significant decreases in the cumulative number of new active brain lesions detected by MRI compared with placebo. No differences were found between ponesimod and placebo in terms of annual rate of relapse.

Another S1P receptor modulator ONO-464 (sponsor: Merck / Ono Pharmaceuticals) has been tested in a randomized, placebo-controlled Phase 2 study. ONO-464 resulted in a significant (77% to 92%) decrease in the number of brain lesions detected by MRI compared with placebo.

In contrast to the agents described above, another new drug Pleneva (BGC-20-0134) (sponsor: BTG) modulates immune system function by restoring balance between pro-inflammatory cytokines (a type of protein that recruits and directs immune cells to the site of inflammation) and anti-inflammatory cytokines. The drug works on the theory that the autoimmune response, such as that seen in MS, results from a loss of balance within the immune system. Pleneva is currently being tested for use in MS in a Phase 2 study.

Written by: Jonathan Simmons | Last reviewed: May 2015.
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