Temelimab is a new treatment under investigation for relapsing remitting and progressive multiple sclerosis (MS). It is taken as an intravenous infusion (drip).
Temelimab for relapsing remitting and progressive MS: Phase II
- Temelimab blocks the effect of a protein found in MS brain lesions which has been shown to cause inflammation and reduce remyelination.
- Clinical trial results suggest that temelimab may promote remyelination. It does not appear to have an effect on relapse rates or new active lesions seen on MRI scans.
- No significant side effects have been reported.
Human endogenous retroviruses (HERV) are sometimes called fossil viruses because they are pieces of ancient viral infections which were incorporated into our DNA millions of years ago. One of these HERVs produces a protein (HERV-W Env) which is found in MS lesions. The protein has been shown to reduce the brain's ability to remyelinate cells by preventing the development of oligodendrocytes, cells which maintain the myelin coating of nerve cells; the protein also activates microglia, immune cells that cause inflammation in the brain.
Temelimab blocks the action of this protein and laboratory studies have indicated that it could promote remyelination, thereby slowing down or stopping MS progression.
Temelimab is taken as an intravenous infusion, once a month.
What are the results so far?
The results of phase II studies have suggested that temelimab may have neuroprotective effects.
CHANGE-MS (also known as GNC-003)
This study recruited 270 participants with relapsing remitting MS. Participants took one of three doses of temelimab or placebo for 24 weeks. After 24 weeks, those in the placebo group were randomized to receive one of the three temelimab doses for a second 24-week period. Individuals who had been receiving temelimab during the first 24-week period continued with their original doses for the second period.
Further details of this study.
ANGEL-MS (also known as GNC-004)
This study was an extension of CHANGE-MS. 220 participants from CHANGE-MS continued to take temelimab for a further 48 weeks.
Further details of this study.
The main measure of the study was the number of active lesions visible on MRI scans at week 24; other measures including presence of other types of lesions, brain tissue loss (atrophy), improvement in MRI markers of remyelination (magnetization transfer ratio) were also taken during the course of the two phases of study.
Results of these two studies have been published.
At 24 weeks, there was no difference in the number of active lesions between the three doses of temelimab and placebo. People who had taken the highest dose of temelimab throughout the study had fewer T1-hypointense lesions. This type of lesion, also known as a black hole, is associated with MS disability and progression. There was also a reduction in brain tissue loss and improvement in MRI markers of remyelination.
These two studies have not shown an effect on relapse rate or active MRI lesions, indicating that temelimab has little effect on the inflammatory MS activity which is responsible for relapses. However, its effect on MRI markers suggest that it may promote remyelination and prevent loss of nerves.
What further research is planned?
The researchers consider that the doses of temelimab used in CHANGE-MS and ANGEL-MS were too low and that some effects of temelimab may have been masked by inflammatory MS activity. The manufacturer has set up a study to evaluate higher doses of temelimab in people with relapsing remitting MS which is progressing in the absence of relapses.
ProTEct-MS (also known as GNC-401)
The study has recruited 41 participants with relapsing remitting MS whose disability has increased despite taking a highly effective disease modifying drug (rituximab) for at least 12 months. The increase in disability in the absence of relapses is known as progression independent of relapses, or PIRA. Participants are taking higher doses of temelimab or placebo for 48 weeks. The main aim of the study is to check that higher doses are safe and well-tolerated. MRI markers of progression are also being captured.
Estimated completion date January 2022.
Further details of this study.
Preliminary results from this study have been released by the manufacturer and presented at a scientific meeting in 2022. After one year of treatment, the higher doses of temelimab were well tolerated with no treatment-related discontinuations of treatment.
The results also showed some benefit to aspects of neurodegeneration measured by MRI. The combination of temelimab and rituximab protected against loss of brain volume (cortical thickness) by more than 50% compared to rituximab alone. Cortical tissue integrity was improved with temelimab, which may demonstrate evidence of remyelination.
In clinical trials, there was no significant difference in side effects reported between people taking temelimab or placebo. Amongst those taking temelimab, one person was diagnosed with breast cancer 20 months after treatment and one person developed drug-induced liver damage which initially improved, then came back again.
