FDA OKs Siponimod, First Oral Drug for Active Secondary Progressive MS

Novartis’ siponimod (Mayzent) is approved for adults with active secondary progressive multiple sclerosis, clinically isolated syndrome, and relapsing-remitting disease.

Officials with the FDA have approved Novartis’ siponimod (Mayzent) tablets, the first oral drug specifically for patients with active secondary progressive multiple sclerosis (SPMS), according to a press release.

In addition to treating SPMS, siponimod is also indicated for the treatment of adults with other relapsing forms of multiple sclerosis (MS), including clinically isolated syndrome and relapsing-remitting disease. Novartis said that it expects siponimod to be available in the United States in approximately 1 week, according to the release.

Siponimod is a sphingosine-1-phosphate receptor modulator that targets subtypes 1 and 5 in the treatment of SPMS. SPMS is often characterized by progressive and irreversible neurological disability and most patients gradually transition from relapsing-remitting MS to SPMS over time.

The approval was based on data from the EXPAND phase 3 clinical trial, which included 1651 individuals with varying levels of disability. The study, which is the largest controlled trial of patients with SPMS, compared the safety and efficacy of siponimod versus placebo. At the study’s initiation, patients had a mean age of 48 years, had been living with MS for approximately 16 years, and more than 50% had a median Expanded Disability Status Scale score of 6.0 and relied on a walking aid.

According to the results, siponimod significantly reduced the risk of 3-month confirmed disability progression (CDP) (primary endpoint; 21% reduction versus placebo, p=0.013; 33% reduction versus placebo in patients with relapse activity in the 2 years prior to screening, p=0.0100). The study showed that siponimod also meaningfully delayed the risk of 6-month CDP (26% versus placebo, p=0.0058) and reduced the annualized relapse rate by 55%.

Additionally, significant favorable outcomes were demonstrated in other relevant measures of MS disease activity, such as cognition, MRI disease activity, and brain volume loss. Participants with non-active SPMS did not show significant benefits.

The most common adverse reactions reported in the study were headache, hypertension, and transaminase increase.

“With the approval of Mayzent, we now have a much-needed therapeutic option to address SPMS with active,” EXPAND Steering Committee member Bruce Cree, MD, PhD, MAS, clinical research director and George A. Zimmerman Endowed Professor in multiple sclerosis at the University of California, San Francisco, School of Medicine, said in a statement. “Importantly, health care professionals now have even more reason to help patients identify changing symptoms and uncover early signs of progression.”

Siponimod is taken orally once daily. Patients will not require a first dose observation unless they have certain pre-existing cardiac conditions, according to Novartis.

References

Novartis receives FDA approval for Mayzent (siponimod), the first oral drug to treat secondary progressive MS with active disease [news release]. https://www.novartis.com/news/media-releases/novartis-receives-fda-approval-mayzent-siponimod-first-oral-drug-treat-secondary-progressive-ms-active-disease. Accessed March 27, 2019.