New Drug Shows Promise for Progressive Form of MS

In a phase 2 clinical trial, an investigational anti-inflammatory drug called ibudilast was found to be superior to placebo in slowing the progression of brain atrophy in patients with progressive multiple sclerosis. The study, conducted at 28 sites around the country, including Columbia University Irving Medical Center, was published Aug. 30 in the New England Journal of Medicine.

Why it Matters

About a dozen drugs have been approved for the treatment of relapsing-remitting MS, but few therapies are available for the progressive stage of the disease.

“We’re very encouraged by the results. This opens a new avenue of hope for patients with progressive MS, which has been very difficult to treat,” says study co-author Claire S. Riley, MD, assistant professor of neurology at Columbia University Vagelos College of Physicians and Surgeons and medical director of the Multiple Sclerosis Center at Columbia.


MS is characterized by a breakdown of myelin, a fatty substance that surrounds axons (part of the nerve cell that transmits signals between brain cells). When myelin degrades, communication between brain cells slows down, causing symptoms such as muscle weakness and problems with thinking and memory. In the most common form of the disease, relapsing-remitting MS, symptoms occur then disappear for weeks or months. Most people with relapsing-remitting disease eventually develop secondary progressive MS, in which symptoms worsen as the brain atrophies. About 15 percent of MS patients have primary progressive MS, in which the disease progresses with the onset of symptoms, without early relapses or remissions. MS is estimated to affect 400,000 people in the United States and 2 million people worldwide.

Ibudilast, which is made by MediciNova, has been marketed in South Korea and Japan since 1989 for the treatment of dizziness after stroke and bronchial asthma. In the United States, it is being studied as a treatment for ALS (another neurodegenerative disorder) and for drug addiction.

What’s New

In this trial, 255 patients with primary or secondary progressive MS were randomized to receive oral ibudilast or placebo for almost two years. The patients ranged in age from 18 to 65, with an average disease duration of 12 years. Using magnetic resonance imaging, the researchers found that patients taking ibudilast had 48 percent less brain atrophy compared with controls. The drug was well tolerated but was associated with higher rates of gastrointestinal side effects, headache, and depression than placebo.

What it Means

Ibudilast appears to be safe and effective for the treatment of patients with progressive MS, although phase 3 clinical trials must demonstrate the drug’s effectiveness in clinical outcomes before it can receive FDA approval. 

What’s Next 

MedicaNova is currently looking at opportunities to begin phase 3 trials of ibudilast in patients with progressive MS.


This study looked at brain volume, not symptoms. However, brain shrinkage in MS is usually associated with declines in physical and cognitive function. “We can detect brain volume changes more accurately than changes in physical or cognitive function, which is why the study used brain volume change as the primary outcome,” explains Riley. “This allowed us to obtain results over a shorter period of time with fewer patients. Further studies are needed to determine if ibudilast has any effect on symptoms or neurologic disability.”

The drug was tested only in patients with progressive MS, not those with relapsing-remitting disease. If phase 3 trials prove that ibudilast is effective for those with progressive MS, it may be considered for use in a broader swath of the MS population, says Riley.

More Info

The study, “Phase 2 Trial of Ibudilast in Progressive Multiple Sclerosis,” was published Aug. 30, 2018, in the New England Journal of Medicine.

Claire S. Riley is assistant professor of neurology and medical director of the Multiple Sclerosis Center at Columbia University Vagelos College of Physicians and Surgeons.

The other authors are listed in the paper.

The study was supported by grants from the National Institute of Neurological Disorders and Stroke (U01NS082329), the National Multiple Sclerosis Society, and MediciNova.