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SAN DIEGO – Early results of the novel human endogenous retrovirus-W antagonist GNbAC1 in a phase 2 trial of patients with relapsing-remitting multiple sclerosis demonstrated evidence of remyelination at week 24 among high-dose users, but it did not meet its primary endpoint of active lesions seen on MRI.
In an interview at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis, study author Robert Glanzman, MD, said that GNbAC1 is a monoclonal antibody that targets and blocks the envelope protein pHER-W ENV, a potent agonist of Toll-like receptor 4. It thereby inhibits TLR4-mediated pathogenicity, which includes activation of macrophages and microglia into proinflammatory phenotypes and direct inhibition of remyelination via TLR4.
In a study known as CHANGE-MS, 270 patients with relapsing-remitting MS were randomized to one of three doses of the GNbAC1 (6, 12, or 18 mg/kg), or placebo via monthly IV infusion over 6 months. The study was conducted at 70 centers in 13 European countries over the past 3 years. It had a 24-week, double-blind, placebo-controlled period, followed by a 24-week, dose-blind, active-only treatment period, with placebo patients randomized to the three different doses of GNbA1C. Brain MRI scans were performed at weeks 12, 16, 20, 24, and 48, to look for evidence of remyelination.
The mean age of patients was 38 years and 65% were female. The researchers observed no safety concerns and no significant effect on inflammatory measures over weeks 12-24, even though the absolute number of lesions was reduced by about 50%. Although the primary endpoint of the cumulative number of gadolinium-enhancing lesions seen on brain MRI scans every 4 weeks during weeks 12-24 was not met, post hoc analyses suggest a decrease in neuroinflammation in the 18 mg/kg GNbA1C group at week 24, compared with placebo (P = .008). “A consistent increase in MT [magnetization transfer] ratio signal was observed in normal-appearing white matter and cerebral cortex at the highest dose, suggesting remyelination,” Dr. Glanzman added. “We gained about a quarter or half of percent in normal-appearing white matter at the cerebral cortex at the high dose. Normally, MS patients lose white matter over time, both in the cortex and in gray matter. We’re actually showing evidence of remyelination, which is really exciting. If these data are replicated and confirmed at week 48, we think we really have an exciting compound.”
GeNeuro sponsored the study.
Full 48-week analyses from CHANGE-MS are expected to be unveiled at the 2018 annual meeting American Academy of Neurology.
SOURCE: Glanzman R et al. Abstract P034.
SAN DIEGO – Early results of the novel human endogenous retrovirus-W antagonist GNbAC1 in a phase 2 trial of patients with relapsing-remitting multiple sclerosis demonstrated evidence of remyelination at week 24 among high-dose users, but it did not meet its primary endpoint of active lesions seen on MRI.
In an interview at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis, study author Robert Glanzman, MD, said that GNbAC1 is a monoclonal antibody that targets and blocks the envelope protein pHER-W ENV, a potent agonist of Toll-like receptor 4. It thereby inhibits TLR4-mediated pathogenicity, which includes activation of macrophages and microglia into proinflammatory phenotypes and direct inhibition of remyelination via TLR4.
In a study known as CHANGE-MS, 270 patients with relapsing-remitting MS were randomized to one of three doses of the GNbAC1 (6, 12, or 18 mg/kg), or placebo via monthly IV infusion over 6 months. The study was conducted at 70 centers in 13 European countries over the past 3 years. It had a 24-week, double-blind, placebo-controlled period, followed by a 24-week, dose-blind, active-only treatment period, with placebo patients randomized to the three different doses of GNbA1C. Brain MRI scans were performed at weeks 12, 16, 20, 24, and 48, to look for evidence of remyelination.
The mean age of patients was 38 years and 65% were female. The researchers observed no safety concerns and no significant effect on inflammatory measures over weeks 12-24, even though the absolute number of lesions was reduced by about 50%. Although the primary endpoint of the cumulative number of gadolinium-enhancing lesions seen on brain MRI scans every 4 weeks during weeks 12-24 was not met, post hoc analyses suggest a decrease in neuroinflammation in the 18 mg/kg GNbA1C group at week 24, compared with placebo (P = .008). “A consistent increase in MT [magnetization transfer] ratio signal was observed in normal-appearing white matter and cerebral cortex at the highest dose, suggesting remyelination,” Dr. Glanzman added. “We gained about a quarter or half of percent in normal-appearing white matter at the cerebral cortex at the high dose. Normally, MS patients lose white matter over time, both in the cortex and in gray matter. We’re actually showing evidence of remyelination, which is really exciting. If these data are replicated and confirmed at week 48, we think we really have an exciting compound.”
GeNeuro sponsored the study.
Full 48-week analyses from CHANGE-MS are expected to be unveiled at the 2018 annual meeting American Academy of Neurology.
SOURCE: Glanzman R et al. Abstract P034.
SAN DIEGO – Early results of the novel human endogenous retrovirus-W antagonist GNbAC1 in a phase 2 trial of patients with relapsing-remitting multiple sclerosis demonstrated evidence of remyelination at week 24 among high-dose users, but it did not meet its primary endpoint of active lesions seen on MRI.
In an interview at ACTRIMS Forum 2018, held by the Americas Committee for Treatment and Research in Multiple Sclerosis, study author Robert Glanzman, MD, said that GNbAC1 is a monoclonal antibody that targets and blocks the envelope protein pHER-W ENV, a potent agonist of Toll-like receptor 4. It thereby inhibits TLR4-mediated pathogenicity, which includes activation of macrophages and microglia into proinflammatory phenotypes and direct inhibition of remyelination via TLR4.
In a study known as CHANGE-MS, 270 patients with relapsing-remitting MS were randomized to one of three doses of the GNbAC1 (6, 12, or 18 mg/kg), or placebo via monthly IV infusion over 6 months. The study was conducted at 70 centers in 13 European countries over the past 3 years. It had a 24-week, double-blind, placebo-controlled period, followed by a 24-week, dose-blind, active-only treatment period, with placebo patients randomized to the three different doses of GNbA1C. Brain MRI scans were performed at weeks 12, 16, 20, 24, and 48, to look for evidence of remyelination.
The mean age of patients was 38 years and 65% were female. The researchers observed no safety concerns and no significant effect on inflammatory measures over weeks 12-24, even though the absolute number of lesions was reduced by about 50%. Although the primary endpoint of the cumulative number of gadolinium-enhancing lesions seen on brain MRI scans every 4 weeks during weeks 12-24 was not met, post hoc analyses suggest a decrease in neuroinflammation in the 18 mg/kg GNbA1C group at week 24, compared with placebo (P = .008). “A consistent increase in MT [magnetization transfer] ratio signal was observed in normal-appearing white matter and cerebral cortex at the highest dose, suggesting remyelination,” Dr. Glanzman added. “We gained about a quarter or half of percent in normal-appearing white matter at the cerebral cortex at the high dose. Normally, MS patients lose white matter over time, both in the cortex and in gray matter. We’re actually showing evidence of remyelination, which is really exciting. If these data are replicated and confirmed at week 48, we think we really have an exciting compound.”
GeNeuro sponsored the study.
Full 48-week analyses from CHANGE-MS are expected to be unveiled at the 2018 annual meeting American Academy of Neurology.
SOURCE: Glanzman R et al. Abstract P034.
REPORTING FROM ACTRIMS FORUM 2018
Key clinical point:
Major finding: Although the primary endpoint was not met, post hoc analyses suggest a decrease in neuroinflammation in the 18 mg/kg GNbA1C group at week 24, compared with placebo (P = .008).
Study details: A phase 2 study of 270 patients with relapsing-remitting MS who were randomized to one of three doses of GNbAC1.
Disclosures: Dr. Glanzman is chief medical officer for GeNeuro, which sponsored the study.
Source: Glanzman R et al. Abstract P034.