Temelimab (formerly GNbAC1)
Experimental Medications: Monoclonal Antibodies
Company: GeNeuro SA
- Intravenous (IV) medication in monthly 6-mg, 12-mg, or 18-mg/kg doses
- Being studied in RMS
Temelimab (GNbAC1) targets a human endogenous retrovirus (HERV) believed to play a role in the development of MS. This treatment approach, or mechanism of action, differs from those of currently approved medications. HERVs are genetic elements that are either hereditary, replicated from a host cell, or result from a germ. The viral envelope protein encoded by one HERV has been found in active MS lesions. Temelimab, a monoclonal antibody, is formulated to neutralize this protein and, thus, it is hoped, block harmful inflammation and facilitate restoration of the myelin sheath that coats nerve fibers and that is damaged in MS. The agent is also being studied in Type 1 diabetes and other autoimmune disease.61
In the Phase IIb CHANGE-MS trial, MRI findings were used to assess the impact of temelimab on MS lesions in the central nervous system. A total of 270 people with relapsing forms of MS were randomized in a near 1:1:1:1 ratio to receive monthly IV infusions of temelimab in doses of 6, 12, or 18 mg per kilogram of body weight or placebo for 24 weeks. After week 24, participants in the placebo group were randomized to receive one of the three temelimab doses for a second 24-week period. Individuals who had been receiving temelimab during the first 24-week period kept receiving their original doses for the second period.
After 48 weeks, temelimab use was associated with significant reductions in both central nervous system deterioration and development of T1-enhancing hyperintense lesions measuring at least 3 millimeters in diameter. These improvements were more substantial among those who had received temelimab for 48 weeks, compared with those who started with placebo, underscoring the potential effectiveness of temelimab as a long-term treatment. In most measures, benefits were dose-dependent: The higher the dose, the more substantial the benefit.62 Temelimab has also shown ongoing benefit over the longer term. The ANGEL-MS study was designed to examine the safety and efficacy of the medication over roughly two years of treatment. Individuals who had participated in the CHANGE-MS trial were offered the opportunity to continue receiving treatment in ANGEL-MS. Ninetyfour percent of eligible patients (219) opted to enter the trial; each received the same dose of temelimab that he or she had been receiving at the conclusion of CHANGE-MS. Although the study was ended early when one of the companies involved in developing temelimab ended its partnership with the other company involved, 154 patients received temelimab for at least 96 weeks.
Data from this study found that the medication had a positive effect of reducing brain atrophy, maintaining the integrity of myelin, and measures of impact on slowing MS progression, with the 18 mg/kg dose having the greatest benefit. GeNeuro, the Swiss company developing temelimab, notes that because the protein temelimab targets “has no known physiological function,” temelimab was anticipated to have a good safety profile, with no effect on the patient’s immune system, which has been shown in clinical trials conducted thus far.63