In a clinical trial, published on March 29, 2021, in JAMA Neurology, ponesimod (marketed under the brand name Ponvory) was found to reduce fatigue significantly better than teriflunomide (Aubagio), another commonly used drug in the treatment of RMS. In addition, the drug was found to surpass teriflunomide in lowering the MS relapse rate in study participants and in reducing the risk of new or enlarging lesions seen on magnetic resonance imaging (MRI) scans. Ponesimod was approved by the U.S. Food and Drug Administration (FDA) in March 2021 for use in adults with various types of RMS, including clinically isolated syndrome (CIS), relapsing-remitting MS (RRMS), and active secondary-progressive MS (SPMS). People with “active” secondary-progressive MS have experienced symptom progression and increased disability but still also experience relapses or have new lesions appear in their MRI scans. Ponvory, which comes in tablet form, is taken orally, once daily. Treatment is initiated with a 14-day starter pack of gradually increasing doses. The maintenance dose is 20 milligrams (mg) per day. Ponvory works similarly to Gilenya (fingolimod), Mayzent (siponimod), and Zeposia (ozanimod), three other MS disease-modifying therapies. All of these drugs are thought to act by retaining certain white blood cells (lymphocytes) in the body’s lymph nodes, keeping them out of circulation and preventing them from entering the central nervous system.
Head-to-Head Study Shows Superior MS Fatigue Reduction
“Fatigue is a common and troubling symptom of MS, meaning it has a significant impact on quality of life in people [with the condition] and, at present, we don’t have easy, quick ways to help them,” says Robert Fox, MD, a staff neurologist and vice chair for research at the Cleveland Clinic’s Mellen Center for MS in Ohio, and coauthor of the study. “What’s encouraging about our study is that we have shown that ponesimod is more effective at reducing fatigue in people with RMS than teriflunomide.” He adds, “This doesn’t mean that other therapies, including teriflunomide, don’t help with MS fatigue. We don’t really know that yet. It just means that compared with teriflunomide, ponesimod offers more and is better at reducing fatigue.” More than 75 percent of people with RMS report fatigue as a symptom, according to recent research, and Dr. Fox hopes that his research on ponesimod will spur additional head-to-head studies comparing currently available and new RMS treatments in terms of fatigue reduction.
Fatigue, Symptom, and Impact Questionnaire Allows Study Participants to Self-Assess
For this study, Fox and his colleagues enrolled more than 1,100 adults between the ages of 18 and 55 years, all of whom had confirmed RMS. About half of them received ponesimod at the 20-mg-per-day dose for more than two years, while the rest of the participants were given 14 mg per day of teriflunomide, which was approved by the FDA for the treatment of relapsing-remitting MS in 2012. In addition to standard MS treatment measures such as disability and relapse rate, participants in the study were evaluated using a specially developed scale called the fatigue, symptom, and impact questionnaire-RMS (FSIQ-RMS). The FSIQ-RMS, developed by Janssen, makers of ponesimod, is a 20-item questionnaire designed to allow people with RMS to self-assess fatigue symptoms, their severity, and their impact on physical activity and cognitive and emotional function, Fox notes. RELATED: New Study Suggests Measuring MS Disability Differently While average weekly FSIQ-RMS scores increased by an average of nearly four points on the 100-point scale among participants treated with teriflunomide, they actually declined slightly among those given ponesimod, Fox says. “Ponesimod has a known efficacy and safety profile in MS, so the fact that it works in terms of reducing relapse rate and disability in our study wasn’t a big surprise,” he explains. “However, the fact that it helps with fatigue was significant.” The most common adverse reactions to Ponvory reported in clinical trials were upper respiratory tract infection, elevation of certain liver enzymes, headache, and hair loss.
