Temelimab, GeNeuro’s investigative treatment for multiple sclerosis (MS), showed a favorable safety profile when given alongside rituximab, according to preclinical safety experiments performed in preparation for the company’s new Phase 2 trial involving patients with relapsing MS.
Data from the preclinical experiments, along with details of the new trial design, will be presented at the MSVirtual2020 meeting, being held online Sept. 11-13. The findings will be presented in a poster, titled “Temelimab for prevention of neurodegeneration: preclinical safety profile and design of the ProTEct-MS (temelimab following rituximab in RMS) study.”
Previously known as GNbAC1, Temelimab is a monoclonal antibody — a protein produced by the body’s immune system — that’s designed to neutralize pHERV-W. pHERV-W is a viral protein that is known to contribute to the inflammation and myelin destruction that characterize MS. Of note, myelin is the fatty sheath that wraps around and protects nerve endings, and is gradually destroyed over the course of MS.
Rituximab — a cancer therapy used off-label in MS — is a monoclonal antibody that lowers the levels of immune B-cells that are known drivers of inflammation in MS.
Here, the researchers hypothesized that a combination of temelimab and rituximab could represent a new therapeutic approach for treating MS. The underlying idea is that temelimab treatment can address disability progression in MS patients whose disease is controlled by the anti-inflammatory therapy rituximab, but whose disability is increasing without relapses. The two therapies together may therefore keep to a minimum inflammation and neurodegeneration in the central nervous system (CNS), composed of the brain and spinal cord.
To test this combination, GeNeuro earlier this year launched a Phase 2 trial called ProTEct-MS. It will assess the safety and effectiveness of temelimab when given to patients with relapsing forms of MS who had previously been treated with rituximab for one year.
The study, which enrolled its first patient back in June, is expected to recruit up to 40 people with relapsing MS whose disability progressed in the absence of relapses.
Participants in the study, which will take place at the Karolinska Institutet’s Academic Specialist Center (ASC) in Stockholm, will be randomly assigned to receive one of three monthly doses of intravenous (into-the-vein) temelimab (18, 36 or 54 mg/kg), or a placebo, for 48 weeks.
The trial’s main goal is to assess the safety and tolerability of temelimab. Additional goals include assessing the effects of the treatment on brain atrophy (shrinkage) and lesion volume, both assessed by MRI scans.
Before proceeding with the study, GeNeuro carried out a series of preclinical safety experiments using lab-cultured peripheral blood mononuclear cells (PBMCs) — different types of immune cells circulating in the blood — and an ex-vivo (outside-the-body) system containing fresh human blood collected from five donors to test if temelimab could safely be given alongside rituximab.
Experiments performed in lab-cultured PBMCs and on the ex-vivo blood loop system revealed that, when given together, temelimab and rituximab did not have any negative effect on the different blood parameters tested, including cytokine levels. Cytokines are molecules that mediate immune and inflammatory reactions in the body.
Additionally, the experiments revealed that neither medication interfered with the activity of the other, suggesting that both can safely be given together, or sequentially within a short period of time.
“Preclinical safety experiments of the drug combination showed no evidence against the use of TML [temelimab] following RTX [rituximab] in humans,” the investigators wrote in the abstract.
According to GeNeuro, around a fourth of the patients expected to participate in ProTEct-MS should already be assigned to their treatment regimens by the end of September. The results of the study are expected in 2021.
ProTEct-MS builds upon positive data from a previous Phase 2 trial, called CHANGE-MS (NCT02782858), and its extension, the Phase 2b ANGEL-MS (NCT03239860) study. Those studies showed that temelimab helped maintain myelin integrity, reduced brain atrophy, and slowed disease progression in patients with relapsing-remitting multiple sclerosis (RRMS).
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