PARIS — A monoclonal antibody directed against a human retroviral protein thought to play a role in the multiple sclerosis (MS) disease process did not show a significant effect on the primary endpoint of a new phase 2 study: the number of gadolinium-enhancing (Gd+) lesions seen on monthly brain MRI scans from weeks 12 to 24 vs placebo.
However, a post hoc analysis suggested the antibody, known as GnbAC1, in development by GeNeuro and Servier, may have an anti-inflammatory effect in active patients at the highest (18 mg/kg) of the three doses tested at week 24. In addition, at the same dose, a “promising” effect on remyelination was observed.
The CHANGE-MS study was presented here at last week’s 7th Joint European Committee for Treatment and Research in Multiple Sclerosis-Americas Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS-ACTRIMS) 2017 meeting.
“This is a completely novel therapeutic approach to multiple sclerosis directly targeting a potential cause of the disease, which appears to promote remyelination without directly affecting normal immunity,” said lead investigator, Hans-Peter Hartung, MD, University Hospital Düsseldorf, Germany.
“While we failed to show a significant effect on the primary outcome of this study — the number of Gd+ lesions at 6 months — there did appear to be a trend suggesting an effect later in the course,” he commented to Medscape Medical News.
“And a particularly interesting observation was that the agent did seem to be associated with remyelination as documented by increased magnetization transfer ratio (MTR) values on MRI. This effect was very robust and encourages us to pursue this approach further.”
He added: “We are continuing to follow patients, and it will be interesting to see what will happen at week 48. Based on the pharmacokinetic data it looks as if maximum concentrations are only reached after 4 months. We may have just missed an effect on Gd+ lesions at 24 weeks. We are also considering a study in secondary progressive MS where the remyelinating properties of this agent could be more obvious.”
Commenting on the study for Medscape Medical News, Jeremy Chataway, MA, PhD, FRCP, consultant neurologist, National Hospital for Neurology and Neurosurgery, University College London, United Kingdom, said, “This is suggestive early work but the higher dose looked encouraging. We need to wait for more data but there has been much interest in the idea of embedded viral genomes as possible causes of MS. This is an interesting and novel therapeutic approach.”