The GeNeuro agent showed marked reductions in brain atrophy in the thalamus and cerebral cortex through a long-term extension period treating patients with multiple sclerosis.
Hans-Peter Hartung, MD, PhD, the chairman of the Department of Neurology of the University Hospital Dusseldorf
Hans-Peter Hartung, MD, PhD
Results of the ANGEL-MS study suggest that temelimab, also known as GNbAC1, sustained its efficacy through 96 weeks across a number of MRI-based outcomes of neurodegeneration in patients with multiple sclerosis.1
An extension of the phase 2b CHANGE-MS trial (NCT02782858), ANGEL-MS the GeNeuro featured 219 (94.8%) patients who had completed the first 48 weeks. All told, in the combined study periods, 18 mg/kg temelimab was associated with a 42% (P = .058) reduction in the atrophy rate of the cerebral cortex for those treated compared to the control group. Similarly, the reduction in the rate of atrophy of the thalamus was 43% (P = .038).
These data were presented by lead investigator Hans-Peter Hartung, MD, PhD, chairman, department of neurology, University Hospital Düsseldorf, at ECTRIMS 2019, September 11-13 in Stockholm, Sweden. Notably, the study was terminated early due to loss of funding.
“We are excited to see that the long-term data confirm the neuroprotective effect of temelimab in MS, and demonstrate its potential to make significant improvements in the lives of patients with MS against disease progression,” said Jesús Martin-Garcia, MBA, CEO, GeNeuro, in a statement.2 “These clinical results confirm the recent advances in the understanding HERV biology and warrant the continued clinical development of temelimab in multiple sclerosis.”
The treatment is a monoclonal antibody designed to neutralize pHERV-W Env, which plays a causal role in the development of MS. In the extension period, 75 patients, 68 patients and 77 patients enrolled to receive temelimab 6 mg/kg, 12 mg/kg and 18 mg/kg monthly IV infusions, respectively.
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.
Myelin integrity also appeared to be affected by temelimab, with magnetization transfer ratio values increasing >1.5% in the cortical (P <.03 in all bands) and normal-appearing white matter (P <.02 in all bands)—effects which were not driven by an anti-inflammatory effect, according to GenNeuro. 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.
“These data support the potential for temelimab to slow disability progression in MS patients. Higher doses and treatment as adjunctive therapy to immunomodulatory, disease-modifying therapies should be explored in future clinical trials,” Hartung and colleagues wrote.
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 = .014).3
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1. Hartung HP, Cree B, Derfuss T, et al. Neuroprotective effects of temelimab in relapsing-remitting MS patients extend to 96 weeks. Presented at: ECTRIMS 2019; September 11-13, 2019; Stockholm, Sweden. Abstract P1379.
2. GeNeuro’s Temelimab Shows Extended Neuroprotective Effects in Relapsing-Remitting MS [press release].Geneva, Switzerland: GeNeuro; Published September 16, 2019. businesswire.com/news/home/20190915005039/en/GeNeuro%E2%80%99s-Temelimab-Shows-Extended-Neuroprotective-Effects-Relapsing-Remitting. Accessed September 17, 2019.
3. 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.