Fingolimod 0.5 mg an optimal therapy for relapsing-remitting MS

The 0.5-mg dose of fingolimod has a superior benefit-risk profile over the 0.25-mg dose, and was superior to glatiramer acetate (GA) – a widely used, effective drug for multiple sclerosis (MS), for treating adults with relapsing or remitting forms of MS (RRMS), the ASSESS study has shown.

“Fingolimod 0.5 mg therapy met the primary objective of significantly reducing the rate of relapse over 12 months compared with GA therapy,” said the researchers. This was accompanied by greater improvements in several MRI parameters, they added.

Fingolimod 0.5 mg is the first oral disease-modifying therapy approved for RRMS. Evidence shows that annualized relapse rates (ARRs) dropped up to 55 percent with fingolimod 5, 1.25, and 0.5 mg vs interferon or placebo. [N Engl J Med 2010;362:387-401; Lancet Neurol 2014;13:545-556] “[However,] a dose lower than 0.5 mg could be efficacious [and] might have fewer adverse effects than the 0.5-mg dose,” they pointed out.

The team sought to evaluate the efficacy and safety of fingolimod 0.25 mg for RRMS to address the post-approval commitment with the US FDA. A total of 1,064 participants (mean age 40 years, 74 percent women) were randomized 1:1:1 to receive fingolimod 0.5 or 0.25 mg orally QD, or GA 20 mg SC QD, for 12 months. The two fingolimod doses were assessed against GA hierarchically through a step-down* procedure. [JAMA Neurol 2020;doi:10.1001/jamaneurol.2020.2950]

A 41-percent relative reduction in aggregate ARR was seen with fingolimod 0.5 mg vs GA (ARR, 0.15 vs 0.26; p=0.01). With fingolimod 0.25 mg, there was only a 15-percent relative ARR reduction vs GA, which did not reach statistical significance (ARR, 0.22 vs 0.26; p=0.42).

Compared with GA, both fingolimod doses led to fewer new or newly enlarging T2 lesions (mean, 2.6 [0.5 mg] and 3.3 [0.25 mg] vs 5.7; p<0.001 for both) and gadolinium-enhancing (GE) T1 lesions (mean, 0.4 [both fingolimod doses] vs 0.9).

A substantially higher percentage of participants had no new or newly enlarging T2 lesions with both fingolimod doses vs GA (n=156 [0.5 mg] and 155 [0.25 mg] vs 96; p<0.001 for both). A significantly greater fraction of participants were also free from GE T1 lesions with fingolimod 0.5 mg vs GA (n=261 vs 202; p=0.004).

All treatments had no effect on brain volume, given the similar percent changes from baseline brain volume across the study arms (mean, –0.65, –0.64, and –0.56 for fingolimod 0.5 mg, fingolimod 0.25 mg, and GA, respectively). These results dispute those of other studies showing reductions in the rate of brain volume loss with fingolimod vs interferon and placebo, noted the researchers.

Adverse event (AE) rates were similar across study arms (90 percent [fingolimod 0.5 mg], 88 percent [fingolimod 0.25 mg], and 87 percent [GA]). AEs leading to study drug discontinuation were more frequent with GA (14 percent) vs the two fingolimod doses (9 percent [0.5 mg] and 7 percent [0.25 mg]). “[T]he safety profile observed with both [fingolimod] doses was consistent with the profiles observed in other clinical trials of fingolimod 0.5 mg,” said the researchers.

These findings support those of a previous study reflecting the superiority of fingolimod 0.5 mg to frequently used injectable therapies such as IM interferon beta-1a. [N Engl J Med 2010;362:402-415] The more significant effects with fingolimod 0.5 mg in the current study underscore its potential as the optimal efficacious dose of fingolimod in this patient setting, they added.