Is a breakthrough treatment for secondary progressive multiple sclerosis (SPMS) finally on the horizon?
It’s still too early to answer that question, but in a randomized, double-blind, placebo-controlled study, a new Novartis drug called siponimod (BAF132) was able to delay progression of the disease in people with SPMS, many of whom had already reached a stage of advanced disability.
The study, funded by Novartis, included 1,651 participants from 31 countries. The results were recently published in the peer-reviewed journal The Lancet.
After three months of use, siponimod was able to slow down the disease’s effects by 21 percent and reduced the risk of six-month disease progression by 26 percent.
Participants who took a daily oral dose of siponimod also lost less brain volume, had fewer brain lesions, and reduced their number of annual relapses by 55 percent. However, siponimod didn’t improve how well the participants could walk.
The results of this study show that siponimod “can delay disability progression in typical established SPMS patients, where other approaches tested so far have been unsuccessful,” Dr. Ludwig Kappos, a professor at University Hospital of Basel in Switzerland and the principal study investigator, said in a statement. “These data are all the more impressive when considering that the majority of patients already had advanced disability when starting treatment.”
Other experts are more cautiously optimistic, pointing out that siponimod was tested against a placebo and for a relatively short amount of time. “There’s an indication that siponimod could be useful in SPMS, but we need more studies,” said Dr. Jaime Imitola, director of the Progressive Multiple Sclerosis Multidisciplinary Clinic and Translational Research Program at The Ohio State University Wexner Medical Center.
SPMS is an advanced form of MS, an autoimmune disease that disrupts the normal flow of information in the brain as well as between the brain and body. Symptoms vary from person to person, but can include numbness and tingling, trouble walking, extreme fatigue, dizziness, pain, depression, and even paralysis.
The National Multiple Sclerosis Society estimates that more than 2.3 million people have MS worldwide. At least two to three times more women than men are affected.
The majority of people with MS initially receive a diagnosis of relapsing-remitting MS (RRMS). They experience occasional periods of time in which their symptoms improve or may even go away for a while.
But within a decade of initial diagnosis, 50 percent of people with RRMS progress to SPMS. With this form of MS, symptoms no longer wax or wane, but stick around — and get steadily worse.
While researchers are always looking for new treatments for SPMS, so far other potential drugs haven’t produced stellar results. Of the 15 medications approved by the U.S. Food and Drug Administration (FDA) for treatment of RRMS, only one is approved for SPMS.
Siponimod is what’s known as a “disease-modifying therapy.” This is a type of drug that works to keep a disease from getting worse. By binding to lymphocytes, a type of white blood cell, and blocking them from entering the central nervous system, siponimod is able to reduce the inflammation that’s responsible for so many SPMS symptoms.
“The challenge is going to be how to determine who is going to respond to this medicine and who will not,” said Bruce Bebo, PhD, executive vice president of research at the National Multiple Sclerosis Society. “It looks like the younger and closer to the conversion to SPMS you are might be factors that contribute to a response to therapy. But until [siponimod] is used more broadly, it will be hard to know for sure.”
Bebo expects the risks and side effects of siponimod to be similar to the immunosuppressive drug fingolimod (Gilenya), which has a similar mechanism of action. These include a slightly higher risk for infection, slowed heart rate, macular edema, and liver damage.
Novartis plans to file for approval of siponimod for SPMS with the FDA this year, which means it could be available in late 2019 or early 2020.
In the meantime, Imitola stresses that it’s important for patients with MS to get a prompt diagnosis and start treatment with a MS specialist as soon as possible.
“Why wait until a patient is declared to have SPMS, around 10–15 years after relapses, to reduce progression?” Imitola asked. “If you stop the disease in its tracks early on with potent medications, then a patient may never get to SPMS. That is the goal. It’s clear that the next generation of MS medications are changing the natural history of the disease. We need more medications that tackle the neurodegeneration in MS.”