medwireNews: Amiselimod shows potential for the treatment of relapsing–remitting multiple sclerosis, without the cardiac side effects associated with other sphingosine 1-phosphate 1 (S1P1) receptor modulators, phase II study findings show.
Unlike fingolimod, for example, amiselimod did not cause a transient reduction in heart rate, which is “advantageous in the initiation phase of amiselimod treatment”, say the researchers, because it makes titration unnecessary.
At the higher two doses given – 0.2 mg/day and 0.4 mg/day – amiselimod reduced the rate of gadolinium-enhanced T1-weighted lesions between weeks 8 and 24 of treatment by an estimated 61% and 77%, respectively, compared with placebo.
The 103 patients in the placebo group had a median of 1.6 new or enlarged T1-weighted lesions on brain scans reviewed on a monthly basis between weeks 8 to 24, compared with 0.0 for both the 103 patients randomly assigned to amiselimod 0.2 mg/day and the 104 randomly assigned to amiselimod 0.4 mg/day. There was no significant difference between patients receiving placebo and the 105 patients given amiselimod 0.1 mg/day (median 2.0 lesions), however.
The average total number of T1-weighted lesions reduced in a dose-dependent fashion, from 8.3 for patients given placebo and 5.5 for those given amiselimod 0.1 mg to 2.3 and 1.7 for patients receiving 0.2 mg and 0.4 mg of the drug, respectively.
The 0.4 mg dose appeared to have a significant effect on T1-weighted lesions from week 8 that increased steadily until week 24, whereas the 0.2 mg dose had a significant effect from week 12 that peaked and plateaued at week 20.
The researchers note in The Lancet Neurology that amiselimod also had a significant and dose-dependent effect on the total number of new or enlarged T2-weighted lesions from weeks 4 to 24, further supporting the primary endpoint analysis.
And although the MOMENTUM (Safety and efficacy of amiselimod in relapsing multiple sclerosis) trial was not sufficiently powered to draw firm conclusions on amiselimod’s effect on relapse rates, it showed a significant and dose-dependent reduction in the time to first confirmed relapse and the proportion of patients experiencing relapse with amiselimod.
“[T]he consistency of dose-dependent effects across several outcomes suggests that amiselimod is a potential treatment for patients with relapsing multiple sclerosis”, says the team led by Ludwig Kappos (University Hospital Basel, Switzerland).
Peripheral lymphocyte counts were reduced, which the researchers say is to be expected with an S1P1 receptor antagonist, and these were pronounced in most patients by week 4, reaching a nadir by week 8, by which time significant effects on lesions were apparent.
Two patients in the 0.4 mg group withdrew from treatment as a result of low lymphocyte counts, although neither was associated with clinical signs of infection. Otherwise, treatment-emergent adverse events, including infection and cardiac disorders, were similar between the treatment and placebo groups.
Headache and nasopharyngitis were the most common adverse effects among patients taking amiselimod, but no serious treatment-emergent adverse event was reported for more than one patient in each group.
By Lucy Piper
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