Siponimod Provides Large-Scale Evidence for the Ability to Treat SPMS

Robert J. Fox, MD, a neurologist at Cleveland Clinic Mellen Center for MS

Robert J. Fox, MD

Siponimod, marketed as Mayzent, recently achieved approval from the FDA for the treatment of secondary progressive multiple sclerosis (SPMS), making the selective sphingosine 1-phosphate (S1P) receptor modulator as the first approval in the secondary progressive space in more than a decade.¹

It also adds another member to the already double-digit number of the disease-modifying therapies in MS, providing physicians with another tool for their clinical practice. To find out more about the therapy’s potential impact on clinical practice, Robert J. Fox, MD, a neurologist at Cleveland Clinic’s Mellen Center for MS treatment, provided his insight to NeurologyLive^®. Fox has done consultation work with a number of pharmaceutical developers of MS therapies, including Novartis, the manufacturer of siponimod.

Fox was part of the investigational team in the phase 3 clinical trial, EXPAND. In that assessment, the therapy displayed excellent promise, showed a 21% reduction in 3-month confirmed disability progression (P = .013). The trial also showed a 33% reduction in confirmed disability progression compared to placebo in patients with relapse activity in the previous 2 years (P = .0100), and a 26% reduced risk of 6-month confirmed disability progression (P = .0058). The annualized relapse rate was reduced by 55% with siponimod.²

Furthermore, favorable outcomes were observed in measurements of disease activity—cognition, magnetic resonance imaging (MRI) lesions, and brain volume loss—for siponimod-treated patients. Ultimately, the increase in T2 lesion volume was limited by 80% compared to placebo, and more patients were free from gadolinium-enhancing lesions (89%) and from new or enlarging T2 lesions (57%).

NeurologyLive^®: How does this approval change the landscape of SPMS treatment? Are there concerns regarding accessibility?

Robert J. Fox, MD: It’s great to finally have an approved therapy for progressive MS that has a large trial population to support its use in SPMS. Before now, we haven’t had a large trial showing efficacy in SPMS, and we haven’t had regulatory approval for SPMS except for a chemotherapy that we don’t use anymore because of its risks and poor efficacy.

At this point, it’s hard to know what the insurance companies will do with the cost, so I don’t know how widely accessible it will be to patients.

What makes the therapy unique, and does it add to our knowledge of how to approach SPMS and therapeutic development for it?

What makes it stand out to me is the large, broad-based trial of SPMS in which it was evaluated. This is a very large and compelling dataset from which to draw our understanding regarding the drug’s efficacy. Yes, it shows us that SPMS can be treated, particularly when there is evidence for active inflammation.

Is there a specific patient subgroup for which this is most useful?

As we saw when the trial results were first presented, it is more effective in those with active inflammation, which includes those with a recent relapse or new or active lesions on MRI.

What's the next therapy with the most potential to make its way to the clinic?

As this study showed and we also saw in the ocrelizumab primary progressive MS trial, we still don’t have a drug with demonstrated efficacy in the later stages of progressive MS—either secondary progressive MS or primary progressive MS. That remains a very large unmet need in my clinical practice.

REFERENCES

1. Novartis receives FDA approval for Mayzent® (siponimod), the first oral drug to treat secondary progressive MS with active disease [press release]. Basel, Switzerland: Novartis; Published March 26, 2019. novartis.gcs-web.com/Novartis-receives-FDA-approval-for-Mayzent-siponimod-the-first-oral-drug-to-treat-secondary-progressive-MS-with-active-disease. Accessed March 26, 2019.

2. Kappos L, Cree B, Fox R, et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomized, phase 3 study. Lancet. Published online March 22, 2018. doi: 10.1016/S0140-6736(18)30475-6.