GNbAC1 is a selective monoclonal antibody, being developed by GeNeuro, for the treatment of relapsing-remitting multiple sclerosis (RRMS).

How GNbAC1 works

The symptoms of multiple sclerosis (MS) are caused when damage to the myelin sheath (a protective layer that surrounds nerve fibers) results in nerve cells not being able to pass messages effectively. This can be a result of the immune system mistakenly attacking the myelin sheath as foreign and can lead to permanent nerve damage.

One potential cause of this is the activation of MSRV (MS- associated retrovirus), a virus that is commonly present, but inactive in the genome. MSRV has been identified at high levels in the blood of MS patients compared to healthy individuals.

When active, MSRV produces a protein called MSRV-envelope protein, or MSRV-Env, which triggers the immune response. The presence of MSRV-Env in MS has been confirmed in brain lesions that occur due to MS. The MSRV-Env protein may induce chronic inflammation, making it difficult for glial cells (a special type of nerve cell that supports other nerve cells, but does not conduct messages) to become cells that produce new myelin. 

GNbAC1 is an antibody designed to specifically target and bind to MSRV-Env, preventing it from inducing an immune response.

In vitro and in vivo studies showed that GNbAC1 neutralizes MSRV-Env, reducing the inflammatory response and allowing the remyelination repair process to restart.

GNbAC1 in clinical trials

The safety and tolerability of GNbAC1 have been assessed in multiple Phase 1 studies of GNbAC1 in healthy participants (NCT01699555 and NCT02452996).

The results of the first Phase 1 trial (NCT01699555), published in the scientific journal Clinical Therapeutics, demonstrated that in 33 healthy male volunteers GNbAC1 was safe and well-tolerated.

Following this, a randomized, double-blind, placebo-controlled Phase 2a trial was carried out in 10 patients with MS, followed by an open-label extension (NCT01639300). The results of this study (published in the journal, Multiple Sclerosis) and the extension (published in the Journal of Neuroimmunology) were promising, as they confirmed that the therapy is well tolerated over a 12-month period and that a clinical response was observed.

Enrollment of 260 RRMS patients for the Phase 2b study, CHANGE-MS (NCT02782858), was completed in January 2017, at clinical sites throughout 13 European nations. The study, carried out in partnership with Servier, aims to examine if GNbAC1 can reduce the number of active brain lesions compared to a placebo, determined by magnetic resonance imaging (MRI), as well as other measures of nerve damage in the brain. The first results are expected early in the fourth quarter of 2017.

For patients completing the CHANGE-MS study, GeNeuro and Servier set up a long-term extension study called ANGEL-MS, to run for two years. This will assess the effect of GNbAC1 in patients over an extended period, to confirm the tolerance and safety as well as the long-term effect on the patient’s quality of life. The first patient was enrolled in April 2017.

GeNeuro also aims to begin clinical trials in the U.S. in 2017. A Phase 2 trial of GNbAC1 in secondary progressive MS (SPMS) patients is planned.

Other Information

GNbAC1 is administered as an injection. The side effects caused with GNbAC1 in the clinical trials are mostly mild, with the most frequent being the common cold.

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