The 2-year safety and efficacy extension of the CHANGE-MS trial ultimately showed encouraging dose-dependent effects with the 18-mg/kg dose on confirmed 12-week EDSS and 25-foot timed walk scores.
Hans-Peter Hartung, MD, PhD
The findings from the ANGEL-MS study have shown that treatment with temelimab, previously known as GNbAC1, for a 2-year period had a continued, positive impact on measures of disease progression in multiple sclerosis (MS).1
The 2-year safety and efficacy extension of the CHANGE-MS trial ultimately showed encouraging dose-dependent effects with the 18-mg/kg dose of the humanized, monoclonal antibody designed to neutralize pHERV-W on confirmed 12-week Expanded Disability Status Scale (EDSS) scores and the 25-foot timed walk.
“These results are remarkable, and they are coherent with temelimab’s novel mode of action seeking to stop the activation of the brain’s innate immunity and restoring the myelin repair system,” said Hans-Peter Hartung, MD, PhD, the chairman of the Department of Neurology of the University Hospital Düsseldorf and lead investigator of the study. “It offers promise to treat progressive patients with low inflammatory activity and could have potential synergies with existing anti-inflammatory drugs in relapsing MS patients.”
The extension trial included the original groups from the CHANGE-MS trial—doses of 18 mg/kg, 12 mg/kg, and 6 mg/kg, as well as the control arm (originally administered placebo, switched to 1 of 3 treatment arms for the final 6 months). In total, 94% of the originally eligible patients continued forward to ANGEL-MS (n = 219) were included in the trial. According to GeNeuro, despite the early termination of the study due to Servier’s decision to end its partnership with GeNeuro, each patient was offered end-of-study visits. Across both trials, a total of 154 patients received temelimab treatment for 96 weeks or more. For those who did not complete 96 weeks, the end-of-study visit results were used in the analysis, with the last observation carried forward.
Data showed a relative reduction in brain atrophy with the highest dose compared to the control group of 42% and 43% in the cortex and thalamus, respectively (cortex, P
= .058; thalamus, P
= .038). The 18-mg/kg treatment arm also showed a lower probability for 12-week confirmed disability progression (Survival Wilcoxon test, P
These key measures from the magnetic resonance imaging (MRI) data from ANGEL-MS confirm the findings reported from week 48 in the CHANGE-MS phase 2b study, which showed neuroprotective benefit on brain atrophy. The CHANGE-MS data showed relative volume loss reductions of 31% and 72% in cortical and thalamic atrophy, respectively, between the 18-mg/kg dose and the control group (cortical, P
= .045; thalamic, P
Additionally, the ANGEL-MS trial found that that myelin integrity was maintained, as measured by magnetization transfer ratio (MTR) signal across cerebral cortical bands. It showed a consistent improvement of 1.5% to 2% MTR units (P
<.03) in all bands, and a 1.5% to 2.3% MTR units (P
<.02) across normal-appearing white matter bands.
In the 25-foot walk test, only 2.4% of patients the 18-mg/kg arm worsened ≥20% from baseline, compared to 10.2% in the control group. Meanwhile, 23.1% and 13.% of the 12-mg/kg and 6-mg/kg groups, respectively, worsened by ≥20% in the 25-foot walk test.
“We are extremely pleased with this data, which clearly confirm the robust and consistent effects of temelimab on key MRI markers of neuroprotection, and we are excited by the early signs of clinical benefit,” Jesús Martin-Garcia, MBA, the CEO of GeNeuro. “The results of ANGEL-MS confirm the potential of temelimab to act against disease progression, the largest unmet medical need in this indication. It further reinforces our determination to continue the development of temelimab in MS.”
By neutralizing pHERV-W Env, the pathogenic protein thought to be a causal factor in the development of MS, the treatment is theorized to simultaneously block a pathological, neurodegenerative process and help to restore myelin integrity in MS patients. Because pHERV-W Env protein has no known physiological function, temelimab has been expected to have a good safety profile with no effect on the immune system. This, according to GeNeuro, has been borne out by all clinical trials carried out to date.
1. GeNeuro’s ANGEL-MS Phase 2b Extension Study Confirms and Extends the Neuroprotective Effects of Temelimab in MS [press release]. Geneva, Switzerland: GeNeuro; Published March 11, 2019. businesswire.com/news/home/20190312005366/en/GeNeuro’s-ANGEL-MS-Phase-2b-Extension-Study-Confirms. Accessed March 11, 2019.
2. GeNeuro and Servier announce successful 12-month results in neuroprotection for Phase 2b CHANGE-MS Study with GNbAC1 in Multiple Sclerosis [press release]. Geneva, Switzerland, and Paris, France: GeNeuro and Servier; Published March 26, 2018. geneuro.com/data/news/geneuro-pr-positive-12m-results-change-ms-en.pdf. Accessed March 11, 2019.