Secondary Progressive MS Treatment Trial Underway
Numerous trials are underway for people who have secondary progressive multiple sclerosis (MS). One of them is now recruiting and is a Phase III trial with study sites around the world, scores of which are in the United States and Canada.
The trial is enrolling 1,530 individuals who have secondary progressive MS, and the purpose is to evaluate the safety and effectiveness of siponimod (BAF312), an experimental oral drug, compared with placebo. A total of 1,020 patients will receive the experimental drug for 23 to 42 months (maximum, 60) while the remaining 510 will be given placebo.
Secondary progressive MS is a form of the disease that develops in about 80 percent of individuals who have had relapsing-remitting MS for about 15 or more years. The transition from relapsing-remitting MS to secondary progressive MS is usually gradual and can be difficult to recognize at first.
However, over time patients notice that their relapses do not go away completely and they experience a slow and more steady worsening of symptoms and lingering disabilities. The symptoms associated with secondary progressive MS can include bowel and bladder problems, stiffness in the legs, and an increase in fatigue, depression, weakness, incoordination, and cognitive abilities.
Siponimod is made by Novartis Pharmaceuticals AG and is in the same drug class as another MS drug called Gilenya (fingolimod), also made by Novartis. However, siponimod reportedly has been designed to be more selective than its sibling, which was approved in 2010 for relapsing-remitting MS.
Thus far, siponimod has shown itself to be safe and beneficial in patients who have relapsing-remitting MS. That evidence was seen in a Phase II trial that enrolled nearly 300 patients.
In that trial, five different doses of siponimod and placebo were tested, and patients who took the drug showed reductions in combined unique active lesions at 3 months when compared with placebo. In fact, response to siponimod was dose related and ranged from 35 percent reduction in the lowest dosage group (0.25 mg) to 82 percent in the 10-mg group.
Experts believe siponimod works by preventing certain white blood cells in lymph nodes from reaching the central nervous system. Siponimod also seems to have a direct impact on the central nervous system by fighting inflammation.
About the Phase III trial
The new siponimod clinical trial is open to both men and women ages 18 to 60 who have secondary progressive MS (defined as progressive increase in disability over at least 6 months) with a prior history of relapsing-remitting MS. Eligible candidates also must have an EDSS score of 3.0 to 6.5 and relapse of corticosteroid treatment within 3 months.
Other information about the study can be seen on the clinical trial website. Interested MSers should consult their healthcare provider about the trial.
The main objective of the trial is to evaluate the delay in confirmed disability progression based on the EDSS scale. Secondary outcomes include measures of disease activity that include relapse rates, adverse events, abnormal lab tests, mobility scores, and results of MRI scans.
Treatment of secondary progressive MS is a challenge, more so than relapsing-remitting MS. Currently the drug treatments include the available disease-modifying drugs, but for patients who do not experience relapses, these drugs usually do not offer much help. The rheumatoid arthritis drug methotrexate also is used to relieve symptoms.
The Food and Drug Administration has approved mitoxantrone (Novantrone) for treatment of secondary progressive MS, but this drug is associated with leukemia, heart problems, and other serious adverse effects. For that reason, mitoxantrone is usually reserved for selected patients whose disease is progressing rapidly.
New treatment options for secondary progressive MS are needed, and the Phase III trial of siponimod is just one of several studies is some stage of activity. Anyone with secondary progressive MS who would like to be considered for a clinical trial should stay current with the clinical trial website and talk to their doctor about their desire to participate.
Bionews 2014 Jan 27
Selmai K et al. Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomized, phase 2 study. Lancet Neurology 2013 Aug; 12(8): 756-67