- Route of administration: Oral
- Type: Statin
- Emerging treatment for: Progressive MS
- Status: Phase III trial planned
Simvastatin is a cholesterol-lowering drug used for treatment
of vascular disease. The use of simvastatin in treating MS is an
example of drug repurposing, a process in which a commercially
available drug is evaluated for the treatment of a different
How it Works
In addition to its cholesterol-lowering properties, Simvastatin
is thought to exhibit
anti-inflammatory effects and protect nerves from damage,
hence is a viable candidate for the potential treatment of
progressive MS. Specifically, simvastatin interferes with the
activation and entry of harmful
T cells into the
central nervous system.
Research and Results
MS-STAT, a double-blind, phase II clinical trial, examined the effect of high dose simvastatin in 140 progressive MS participants over two years. Participants were administered 80mg simvastatin/day or placebo (inactive version of the drug). Individuals administered with simvastatin showed a significant (43%) reduction in brain atrophy, slower changes in EDSS, and improved scores on the MSIS-29, a measure of the extent to which MS affects daily life compared to placebo. There was no difference between groups in the Multiple Sclerosis Functional Composite (MSFC) score, which measures mobility, dexterity and cognition. The study also showed no differences between groups in levels of inflammation-associated molecules. Overall, the results of this phase II demonstrate that simvastatin has a beneficial effect on brain atrophy and disability in people with secondary progressive MS. These results are encouraging and warrant phase III trials to determine the safety and efficacy of simvastatin on a larger group of people with MS as well as when taken over a longer term.
In a MS-STAT follow-up study, the effect of simvastatin treatment on cognition and quality of life was assessed. Participants took part in numerous tests measuring cognitive and neuropsychiatric issues, and filled in a survey on quality of life throughout the trial. The researchers discovered a positive correlation between simvastatin treatment and improved frontal lobe function and self-reported physical quality of life. There were no differences in placebo and simvastatin groups for other cognitive and neuropsychiatric measures.
A new phase III clinical trial called MS-STAT2 was launched to examine disability progression following treatment with simvastatin in 1180 people with secondary progressive MS. Participants will take either simvastatin (80mg/day) or placebo for three years. The primary outcome measure will be sustained change in disability for six months or more. The clinical trial will begin in Summer 2017 and is expected to continue for six years.
Adverse Effects Reported
The occurrence of serious adverse events was similar between
simvastatin and placebo groups, and simvastatin was well
tolerated with no safety concerns.
Chataway, J et al. Effect of high-dose simvastatin on brain atrophy and disability in secondary progressive multiple sclerosis (MS-STAT): a randomised, placebo-controlled, phase 2 trial. Lancet. 2014; 383(9936):2213-21.
Chan, D et al. Effect of high-dose simvastatin on cognitive, neuropsychiatric, and health-related quality-of-life measures in secondary progressive multiple sclerosis: secondary analyses from the MS-STAT randomised, placebo-controlled trial. Lancet Neurol .2017; 10.1016/S1474-4422(17)30113-8. [Epub ahead of print]