A Phase 2b trial assessing the experimental retroviral-targeting treatment GNbAC1 in patients with relapsing-remitting multiple sclerosis (RRMS) failed to meet its primary goal of reducing brain lesions and other signs of brain inflammation within six months.
But researchers at GeNeuro and Servier — the two European companies that jointly developed the drug — remain optimistic. Since GNbAC1 is designed to fight MS in an entirely new way, it’s possible that its effects won’t be seen until later, they said. The trial, CHANGE-MS, will continue for another six months.
“A longer delay of action than seen with other drugs is possible,” Hans-Peter Hartung, chairman of the neurology department at Germany’s University Hospital Düsseldorf and the study’s principal investigator, said in a press release. “The six-month data showed a good safety profile. From a clinical perspective, it is important to wait for the full 12-month results.”
Unlike other MS drugs, GNbAC1 does not target inflammatory cells. Instead, the antibody aims to neutralize a protein made by a so-called retroviral gene. Human endogenous retroviruses (HERVs) are ancient viruses that incorporate their DNA into the human genome. Researchers believe that retroviral sequences comprise up to 8 percent of the human genome.
GNbAC1 targets a protein found on the viral surface. Studies suggest that this protein might help trigger MS as well as type 1 diabetes.
The CHANGE-MS trial (NCT02782858) enrolled 270 RRMS patients in 12 European countries who were randomly assigned to receive either GNbAC1 or placebo. Its primary goal was a reduction in inflammatory brain lesion load measured by magnetic resonance imaging (MRI) after six months.
But so far, analyses show no significant difference between treated and control patients. And although the entire group of 270 patients had halved their relapse rates compared to the year before the study, there was, again, no significant difference between the groups.
The companies did, however, not report any safety issues with GNbAC1, and the trial will continue as planned.
“In line with Servier’s commitment to bringing new safe and effective treatments to patients, we will continue working with GeNeuro to better understand the potential clinical benefits of this innovative drug, GNbAC1, and wait for the full results of the study at 12 months,” added Christian de Bodinat, director of the French company’s Neuropsychiatry Therapeutic Innovation Pole.
At 12 months, researchers plan to evaluate MRI measures of neurodegeneration, symptoms and disability levels, as well as biomarkers, including retroviral protein levels.
“GNbAC1 is a new way to treat MS patients, with a novel mode of action. Analysis of the data is ongoing to better understand potential therapeutic benefits,” said Jesús Martin-Garcia, CEO of Swiss-based GeNeuro. “We are fully committed to this technology and look forward to final results from this 12-month study, expected in the first quarter of 2018.”
Patients who complete the study will have the option to enroll in a long-term safety and efficacy study (ANGEL-MS, NCT03239860) of GNbAC1.