Temelimab (GNbAC1) is a selective monoclonal antibody that GeNeuro is developing for the treatment of multiple sclerosis (MS). Studies have suggested that Temelimab may reduce the body’s inflammatory response.

How does temelimab work?

The symptoms of MS occur as a result of damage to the myelin sheath that forms around nerves, which leads to nerve cells not being able to pass messages effectively. This results from the immune system mistakenly attacking the myelin sheath and can lead to permanent nerve damage.

One potential cause of such attacks is the activation of MS-associated retrovirus or MSRV, a virus that is commonly present, but inactive, in the genomeWhen active, MSRV produces a protein called MSRV-envelope protein, or MSRV-Env, which triggers an immune response. The presence of MSRV-Env in MS has been confirmed in MS brain lesions

Temelimab is an antibody that researchers designed to specifically target MSRV-Env, preventing it from inducing an immune response.

In vitro — in the lab — and in vivo, or in-the-body studies have shown that temelimab neutralizes MSRV-Env, reducing the inflammatory response. 

Temelimab in clinical trials

Phase 1 studies confirmed the safety and tolerability of temelimab in healthy participants (NCT01699555 and NCT02452996).  

Then researchers confirmed the tolerability of the treatment over a 12-month period in 10 patients with MS in a randomized, double-blind, placebo-controlled Phase 2a trial followed by an open-label extension (NCT01639300).

A Phase 2b study, CHANGE-MS (NCT02782858), then assessed the effect of three dosage levels of temelimab (6, 12, and 18 mg/kg body weight) in reducing the number of active brain lesions. The results showed that patients taking temelimab had a smaller amount of brain atrophy compared with a placebo group; the treatment also was found to be well-tolerated.

Then, a long-term extension study called ANGEL-MS (NCT03239860) assessed the effect of the treatment over a two-year period. The results showed a reduction in brain atrophy. Patients in the 18 mg/kg highest dose group had 42% less atrophy in the brain’s cortex compared with the placebo group. They also had 43% less atrophy in the thalamus of the brain compared with those receiving the placebo. In addition, the treatment group showed continued integrity of the myelin sheath. 

A Phase 1 trial (NCT03574428) investigated the effects of high doses of temelimab in 24 healthy men. The researchers randomly assigned participants to one of four dosages of treatment (36, 60, 85, or 100 mg/kg) or a placebo. Those results showed that no adverse events related to safety occurred in the trial.

Ongoing clinical trials

A Phase 2a randomized, double-blind, placebo-controlled trial, ProTEct-MS (NCT04480307) is currently recruiting up to 40 patients with relapsing forms of MS in Sweden. Patients will have received at least 12 months of treatment with rituximab before beginning temelimab.

The participants will given either 18, 36, or 54 mg/kg of temelimab or a placebo monthly for 48 weeks. The study will investigate the safety and tolerability as well as the pharmacokinetics (movement in the body) and pharmacodynamics (effect on the body) of temelimab. The researchers expect to conclude the trial in September 2021.

GeNeuro also began a Phase 2 trial of temelimab in secondary progressive MS (SPMS) patients. The company had postponed the trial due to COVID-19 but recently announced that it enrolled its first participant. 

Other information

Temelimab is an injection. The side effects of temelimab in clinical trials were mostly mild, with the most frequent being cold-like symptoms.

 

Last updated: Oct. 5, 2020

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