A phase two clinical trial has demonstrated that an anti-inflammatory drug currently used to treat asthma and stroke patients can slow the neurological damage of progressive multiple sclerosis (MS) by nearly 50 percent.
As of now, there are very few medications that are effective at slowing this form of the disease, which is characterized by continual nervous system decline. For unknown reasons, individuals with multiple sclerosis experience a physiological phenomenon, called demyelination, wherein nerve cells throughout the brain and spinal cord (central nervous system) and body (peripheral nervous system) become damaged or destroyed after the fatty coating around their axons is stripped away.
Demyelination is thought to arise from either an autoimmune response or a failure of myelin-producing cells. Though much about the disease remains mysterious, it is clear that inflammation plays a key role. In primary and secondary progressive MS, the inflammatory nerve damage is persistent, leading to worsening disability over time. The other main type, relapsing-remitting MS, manifests as periods of remission interspersed with periods of active inflammation.
The trial included 255 primary or secondary MS patients, aged 21 to 65, from across the US. Of them, 129 were randomly assigned to take the drug, ibudilast, and 126 were assigned a placebo. After two years, patients in both groups showed brain neuron loss, as measured by total brain shrinkage, yet those who took the daily oral medication showed 48 percent less brain tissue loss than those who took the placebo. The complete results are reported in The New England Journal of Medicine.
"These findings are significant for patients with progressive MS,” principal investigator Dr Robert Fox said in a statement. "Our hope is that the benefit of ibudilast in slowing brain shrinkage will also translate to decreased progression of associated physical disabilities in a future phase 3 trial."
Overall, the drug appears to be safe; the rates of both mild to moderate and severe adverse events were similar between groups. Events that were more common in ibudilast patients, and therefore may be side effects, include gastrointestinal upset, depression, and headaches.
Ibudilast has been marketed in Japan and Korea since 1989 but is not yet approved for use in the US. However, the FDA has granted MediciNova, the pharmaceutical company that sponsored the MS trial, "fast track" and orphan drug status for ibudilast as a progressive MS treatment. The former designation means that the agency will expedite their review of the company's new drug application, when filed, based on an urgent need from patients. The latter bestows MediciNova exclusive marketing rights (no generics can be sold) for seven years if it is approved for that indication.
MediciNova is also investigating ibudilast as a potential treatment of amyotrophic lateral sclerosis (ALS), also known as motor neurone disease.