GNbAC1, a Humanized Monoclonal Antibody Against The Multiple Sclerosis Associated Retrovirus Envelope Protein, Is Well Tolerated In Patients With Multiple Sclerosis. (P2.217)

Abstract

OBJECTIVES: To assess the safety, pharmacokinetics and pharmacodynamics over 1 year of GNbAC1, a monoclonal antibody agonist of the Multiple Sclerosis associated Retrovirus (MSRV) Env protein in multiple sclerosis (MS) patients. BACKGROUND: Human endogenous retrovirus (HERV) genes represent 8% of the human genome. Among HERV genes, the Multiple Sclerosis associated Retrovirus (MSRV) DNA contains copies expressing a protein called Env, which can activate a pro-inflammatory and autoimmune cascade via Toll-Like receptor 4. MSRV-Env expressed in multiple sclerosis (MS) plaques has an inhibitory effect on oligodendrocyte precursor cell differentiation and affects remyelination. GNbAC1, a humanised monoclonal antibody, binds MSRV-Env. Blocking MSRV-Env by GNbAC1 is expected to have a neuroprotective effect in MS. DESIGN: We report the results of Phase II single ascending dose study followed by a 12-month open-label extension to evaluate the safety, pharmacokinetics and pharmacodynamics of GNbAC1 in 10 MS patients. First, in Cohort 1, 5 patients were randomized to receive a single intravenous infusion of 2 mg/kg of GNbAC1 or placebo; in Cohort 2, 5 patients were randomized to receive an intravenous infusion of 6 mg/kg of GNbAC1 or placebo. Then, all patients of Cohorts 1 and 2 pursued treatment with 11 GNbAC1 infusions at 2 mg/kg and 6 mg/kg dose respectively at 4-week intervals. RESULTS: Over the long term, GNbAC1 was well tolerated at both doses. No safety or immunogenicity signals were detected. Pharmacokinetic data confirm a dose linear pharmacokinetics with an elimination half-life of 15-17 days compatible with monthly infusions. Pharmacodynamic and MSRV biomarkers are presented. CONCLUSIONS: The 12-month results confirm the favorable long-term GNbAC1 safety profile in MS patients and the pharmacokinetics allows monthly administration scheme. These results support the launch of a larger Phase II study testing the efficacy and safety of the first monoclonal antibody targeting the MSRV-Env protein.

Disclosure: Dr. Derfuss has nothing to disclose. Dr. Curtin has received personal compensation for activities with GeNeuro. Dr. Lang has received personal compensation for activities with GeNeuro as an employee. Dr. Perron has received personal compensation for activities with Geneuro as an employee. Dr. Kappos has received personal compensation for activities with the University Hospital Basel. Dr. Kappos has received research support from the Swiss MS Society, Swiss National Research Foundation, the European Union, Gianni Rubatto Foundation, Novartis, and Roche Diagnostics Corp. Dr. LaLive has received personal compensation for activities with Biogen Idec, Merck Serono, Novartis, Sanofi-Aventis Pharmaceuticals Inc., Teva Neuroscience, Geneuro, and Genzyme Corp. Dr. LaLive has received research support from Biogen Idec, Merck Serono, and Novartis.