BOSTON—Siponimod reduces the risk of three- month and six-month confirmed disability progression in patients with secondary progressive multiple
sclerosis (MS), according to research described at the
69th Annual Meeting of the American Academy of Neurology. The treatment also appears to reduce relapse rate
and the number of new lesions. The study is “the largest
controlled double-blind study in secondary progressive
MS,” according to Ludwig Kappos, MD, Chair of Neurology at University Hospital Basel in Switzerland.
Siponimod is a selective sphingosine 1-phosphate
receptor- 1 and - 5 modulator with effects on the CNS
and the peripheral nervous system. The treatment
may have effects related to remyelination and neuroprotection, according to Dr. Kappos. He and his
colleagues conducted a randomized, double-blind,
placebo-controlled, phase III study to compare the
effects of siponimod and placebo in patients with secondary progressive MS. The investigators randomized
patients 2: 1 to once-daily siponimod ( 2 mg) or placebo. Patients were treated for as long as three years in
the double-blind phase of the study. In a subsequent
extension study, participants were treated for as long
as seven years.
The event- and exposure-driven study’s primary
end point was time to three-month confirmed dis-
ability progression, as assessed by the Expanded
Disability Status Scale (EDSS). Key secondary end
points included time to confirmed worsening of 20%
or more from baseline in the Timed 25-Foot Walk test
(T25FW) and T2 lesion volume change from baseline.
Other secondary end points included six-month con-
firmed disability progression, annualized relapse rate,
12-item MS Walking Scale (MSWS- 12), number of T1
gadolinium-enhancing and T2 lesions, and percent
brain volume change.
The investigators randomized 1,651 patients. The
population’s mean age was 50, and mean EDSS score
was 5. 5. The sample was typical of the population of
patients with secondary progressive MS.
Siponimod reduced the risk of three-month con-
firmed disability progression by 21% versus placebo.
Dr. Kappos and colleagues consistently observed point
estimates in favor of siponimod across predefined sub-
groups, including patients with no relapses in the two
years before study initiation and patients without gad-
olinium-enhancing lesions at baseline.
The risk reduction observed for the T25FW was
6.2%, but was not statistically significant. Siponimod
reduced the risk of six-month confirmed disability
progression by 26%. In addition, siponimod reduced
the annualized relapse rate by 55.5%, the number of
T1 gadolinium-enhancing lesions by 86.6%, and the
number of new T2 lesions by 81%. The relative differences in change from baseline in T2 lesion volume,
MSWS- 12, and percent brain volume change were
79.1%, 39.7%, and 23.4%, respectively, versus placebo. Siponimod’s effects were more pronounced in
patients with relapses at baseline, compared with those
without, said Dr. Kappos. NR
Siponimod Reduces Risk of
Confirmed Disability Progression
in Secondary Progressive MS
The treatment also may reduce annualized relapse rate and the number of new lesions.
The treatment may have effects related
to remyelination and neuroprotection.