While sudden onset of a condition is terrifying for patients and their loved ones, gradual onset, too, brings fear by way of worsening symptoms and slow loss of the individual they were before defined by disease. Such is the devastating case for those diagnosed with primary-progressive multiple sclerosis (PPMS) – a disabling disease of the central nervous system.
In individuals with multiple sclerosis (MS), the immune system attacks the fatty protective myelin sheath that covers their nerve fibers – causing communication problems between the brain and the rest of the body. The disease can result in permanent damage or deterioration of the nerves and eventual death. Most people with MS are diagnosed between the ages of 20 and 50, with at least two to three times more women than men coming down with the disease. It isn't completely clear why MS develops in some people and not others. A combination of genetics and environmental factors appears to be responsible.
Most people, nearly 85% of those with MS, have a relapsing-remitting disease course. They experience periods of new symptoms or relapses that develop over days or weeks and usually improve partially or entirely. These relapses are followed by quiet periods of disease remission that can last months or even years. At least 50% of those with relapsing-remitting MS eventually develop a steady progression of symptoms, with or without periods of remission, within 10 to 20 years from disease onset. This is known as secondary-progressive MS. Approximately 15% of people with MS experience a gradual onset and steady progression of signs and symptoms without any relapses – the subset of MS known as primary-progressive.
There are more than a dozen disease-modifying therapies approved by the FDA to treat MS, but these compounds are only indicated for the most common relapsing-remitting course. Historically, there's been very little doctors could do for their patients with PPMS other than provide medications and other therapies to treat noticeable symptoms – nothing slowed the progression of the disease itself. But a novel therapeutic monoclonal antibody approved in March 2017 represents a different scientific approach to treating PPMS. The drug targets a type of immune cell called CD20-positive B cell that plays a key role in the disease. Given once every six months by an intravenous (IV) infusion, ocrelizumab is the first and only MS treatment to target these specialized cells and treat the primary-progressive population.
Positive results from a Phase III study of the drug showed significantly slower disability progression over a median treatment duration of three years when compared to placebo – patients were 24% less likely to have disability progression for 3 months. Separate analysis of the same study showed greater patient satisfaction after one year with the treatment. More than 120,000 people have been treated with ocrelizumab globally, and data continue to show a consistent and favorable benefit-risk profile in clinical trial and real-world settings.
Other novel work in the MS space includes the recent FDA approval of a drug with a similar method of action. Also targeting the CD20 protein found on the surface of B-cells, ofatumumab became the first MS therapy approved for at-home administration. The FDA ruled on ofatumumab in August 2020. But ocrelizumab remains the only FDA-approved medication for the struggling subset of MS patients with the primary-progressive condition. As a novel treatment made available to a population for which none existed, ocrelizumab is a Top 10 Medical Innovation for 2021.