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The phase 1 trial assessed high doses of the therapy in 24 healthy volunteers, divvied up into 4 cohorts to receive doses, including 36 mg/kg, 60 mg/kg, 85 mg/kg, and 110 mg/kg. These data build upon the findings of the phase 2b CHANGE-MS trial.
Jesús Martin-Garcia, MBA
Early phase trial results have shown positive safety and tolerability indications for temelimab, and investigational therapy developed by GeNeuro, in the treatment of multiple sclerosis (MS) and other autoimmune diseases.1
The phase 1 trial assessed high doses of the therapy in 24 healthy volunteers, divvied up into 4 cohorts to receive doses, including 36 mg/kg, 60 mg/kg, 85 mg/kg, and 110 mg/kg. In this assessment, there were no adverse events related to the trial drug, and pharmacokinetic data were linear for all doses tested.
Temelimab, also known as GNbAC1, is an antibody against the envelope protein (Env) of the endogenous retrovirus pHERV-W with the goal of simultaneously blocking the pathological inflammation process and restore the remyelination process.
“The results from this high-dose study support and expand the large amount of positive clinical data we already have regarding temelimab’s safety, tolerability and efficacy,” Jesús Martin-Garcia, MBA, the chairman and CEO of GeNeuro, said in a statement. “Temelimab is the first treatment targeting an MS mechanism to have shown robust and consistent effects on key neuroprotection markers in clinical trials. The success of this Phase 1 study allows us to explore whether higher doses of temelimab provides additional benefit in MS patients as well as broadening the therapeutic areas for which this drug candidate could be used.”
These data build upon the findings of the phase 2b CHANGE-MS trial, which included 270 patients with relapsing MS. It showed that the highest dose tested of temelimab, 18 mg/kg, was effective in the treatment of patients with MS. It showed a slowed rate of brain atrophy compared to placebo in the thalamus (P = .014) and the cerebral cortex (P = .045). The rate of whole brain atrophy was -0.42% at week 48 with temelimab compared to -0.59% with placebo (P = .079). Ultimately, whole brain atrophy showed a 29% relative decrease over 12 months compared to control. 2
Additionally, the magnetization transfer ratio at 6 months for those on the pHERV-W Env antagonist remained stable, compared to the control group at 12 months, suggestive of a benefit in remyelination. The number of MRI T1 hypointense lesions and lesions with active inflammation was 63% lower at the study’s end in the 18 mg/kg group compared to placebo. As well, the safety and tolerability were consistent with what had been seen.
The clinical trials of the therapy are suggestive of a newer hypothesis about the root cause of MS, which represents early viral DNA incorporated into the human genome millions of years ago. Roughly 8% of the human genome today consists of these viral DNA incorporations.
“Efficacy of GNbAC1 in MS suggests that the initial viral trigger for MS is not simply an early childhood viral exposure that triggers MS in a genetically susceptible individual. These results suggest instead that the initial viral basis of MS is some of the ancient viral DNA in our genome lying dormant within us that is derepressed by environmental viruses (eg, Epstein-Barr virus),” Daniel Kantor, MD, wrote in a 2018 publication.2
GeNeuro previously disclosed that it is continuing discussions with potential partners to define next steps in developing temelimab for MS, while continuing to advance programs in type 1 diabetes and amyotrophic lateral sclerosis (ALS). GeNeuro reacquired the worldwide rights to commercialized and develop the temelimab from Servier in September 2018 after Servier declined to continue its development of the treatment due to strategic, research, and development reasons, among other priorities.3
1. GeNeuro Announces Positive Results from Temelimab (GNbAC1) Phase 1 High-dose Clinical Trial [press release]. Geneva, Switzerland: GeNeuro; Published January 21, 2019. businesswire.com/news/home/20190121005367/en/GeNeuro-Announces-Positive-Results-Temelimab-GNbAC1-Phase. Accessed February 4, 2019.
2. Kantor D. Update on the CHANGE-MS clinical trial results for GNbAC1. Pract Neurol. Published online June 2018. practicalneurology.com/pdfs/PN0618_MM_Change.pdf. Accessed February 4, 2019.
3. GeNeuro Regains Worldwide Rights ex US and Japan to GNbAC1 in Multiple Sclerosis from Servier [press release]. Paris, France, and Geneva, Switzerland: GeNeuro; Published September 18, 2018. geneuro.com/data/news/GeNeuro-PR-CollaborationServier-EN.pdf. Accessed February 4, 2019.