Disease-modifying therapies (DMTs) are the main group of medications used to treat MS. DMTs have varying mechanisms of action and routes of administration and include interferons, glatiramer acetate, teriflunomide, sphingosine 1-phosphate receptor modulators, fumarates, cladribine, and monoclonal antibodies.
In recent years, a number of novel DMTs have been approved, adding to the collection of DMTs now available for treating MS. Read on for an overview of the most recently approved therapies.
|
Brand |
Generic name |
Company |
Year of approval (EU) |
Type |
Indications |
|
Kesimpta® |
Ofatumumab |
Novartis |
2020 |
CD20-directed cytolytic monoclonal antibody |
RRMS, SPMS |
|
Mayzent® |
Siponimod (oral, once daily) |
Novartis |
2020 |
Sphingosine 1-phosphate receptor modulator |
Active SPMS |
|
Zeposia® |
Ozanimod (oral, once daily) |
BMS |
2020 |
Sphingosine 1-phosphate receptor modulator |
RRMS |
|
Ponvory® |
Ponesimod |
Janssen |
2021 |
Sphingosine 1-phosphate receptor modulator |
RRMS, SPMS |
Ofatumumab is a CD20-directed cytolytic antibody (immunotherapy) indicated for the treatment of adult patients with relapsing forms of MS, including clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease.i The approval was based on two phase III trials, ASCLEPIOS I and II, showing a 51% and 58% reduction in annualised relapse rate, respectively, compared with teriflunomide.ii
Siponimod is a sphingosine 1-phosphate receptor modulator indicated for the treatment of adults with MS, specifically active secondary progressive multiple sclerosis (SPMS).iii It was the first oral treatment specifically approved for active SPMS. The approval was based on the phase III trial EXPAND, showing a 21% reduced risk of 3 month confirmed disability progression compared with placebo.iv
Ozanimod is a sphingosine 1-phosphate (S1P) receptor modulator indicated for the treatment of adult patients with relapsing-remitting MS (RRMS) with active disease as defined by clinical or imaging features.v The approval was based on two phase III trials, SUNBEAM and RADIANCE, showing a 48% and 38% reduction in annualised relapse rate, respectively, compared with weekly IFN-b-1a.vi,vii It is the only approved S1P receptor modulator that does not require a genetic test or first-dose observation.
Ponesimod is a sphingosine 1-phosphate receptor modulator indicated for the treatment of adult patients with relapsing MS (which includes people with relapsing remitting and secondary progressive MS) with active disease as defined by clinical or imaging features.viii The approval was based on the OPTIMUM phase III trial showing a 30% reduction in annualised relapse rate compared to teriflunomide.ix
Amongst DMTs in clinical development, inhibitors of bruton’s tyrosine kinase represent an entirely new emerging drug class in MS, with three different drugs entering phase III trials:x
Evobrutinib has completed a phase II study in RRMS, demonstrating a superior effect on imaging, but not clinical outcomes compared with placebo and with phase III testing ongoing
Tolebrutinib recently completed a dose-finding study and will enter phase III testing soon
Fenebrutinib has been tested in other autoimmune conditions and will now directly enter phase III trials in RRMS and primary progressive MS (PPMS)
Ibudilast is an anti-inflammatory medication that works by reducing inflammation in the body and decreasing the action of a specific enzyme known as phosphodiesterase. A phase 3 clinical trial is currently being planned that will evaluate ibudilast in people with SPMS without relapses.
Masitinib is an experimental drug targeted at SPMS and PPMS. It is taken as a tablet, twice daily, and it blocks biochemical processes involved in inflammation and immune responses, targeting both mast cells and microglia. Positive Phase 2B/3 results with masitinib in progressive forms of MS have been reported; masitinib slowed down disease progression in patients, and also demonstrated a significant reduction in the risk of reaching a level of disability severe enough to require wheelchair mobility.
There have also been recent advancements in the use of stem cell therapy for MS, with autologous haematopoietic stem cell transplantation (AHSCT) emerging as a treatment option. It is yet to be determined whether the short-term benefits of AHSCT will outweigh risks, or whether the use of AHSCT may limit a patient’s potential use of other DMTs in the future.xi
Visit Course 4: Treating MS to learn more about the recently approved therapies mentioned in this article.
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