Temelimab works. HERVs clearly implicated.
https://papers.ssrn.com/sol3/papers.cfm ... id=3388820
Background: The envelope protein encoded by pathogenic Human Endogenous Retrovirus type-W (pHERV W-env) has been involved in the pathophysiology of MS. In pre-clinical studies pHERV-W-env directly activated microglia and inhibited remyelination; both mechanisms contribute to MS-related CNS damage. Temelimab (GNbAC1) is a humanised, IgG4-kappa monoclonal antibody that targets pHERV-W-env, neutralising its effects in preclinical models. The aim of this Phase 2 study was to evaluate efficacy and safety of three doses of temelimab in participants with relapsing-remitting MS.
Methods: A 24-week randomised, double-blind, placebo-controlled Period 1 was followed by a 24 week randomised, dose-controlled Period 2 (NCT02782858). Placebo-treated subjects from Period 1 were re-randomised to one of the active treatment arms for Period 2. Six injections were repeated in both periods. Primary endpoint was the cumulative number of Gd-enhancing T1 lesions in monthly brain MRIs from week 12 to 24. Secondary and exploratory endpoints were: hypointense T1 lesion number/volume, T2 lesion number/volume, change in brain volume, change in magnetisation transfer ratio (MTR), clinical relapse, and disability at weeks 24 and 48.
Findings: 270 participants were randomised. The primary endpoint was not met at week 24 (comparison ratio 0.90 (95% CI=0.49-1.64) highest dose vs placebo). 247 participants (91.5% of original cohort) entered Period 2; 236 (87.4%) completed week 48 evaluations. A dose-related decrease of brain atrophy and positive effects on T1 hypointense lesion number and MTR in the 18 mg/kg group were observed at week 48. No safety issue emerged.
Interpretation: This is the first clinical efficacy study of temelimab, a specific anti-HERV-directed therapy. No benefit was seen on inflammatory measures at week 24; however, week 48 data suggests dose-dependent effects of temelimab on 3 neurodegeneration measures: brain atrophy, MTR and T1 hypointense lesions. Temelimab has further development potential as a neuroprotective treatment that specifically blocks deleterious CNS effects of pHERV-W-env in MS.