The repertoire of available multiple sclerosis (MS) disease modifying therapies (DMTs) is constantly growing. In recent years, there have been several new DMTs that have entered the market. In his talk ‘Multiple Sclerosis 2022 – How many more therapies do we need?’ at the MS State of the Art Symposium, Prof. Dr Andrew Chan from the University of Bern discussed DMTs that have recently been approved in Switzerland and recent developments in the field of MS.

Which new MS DMTs have been approved in Switzerland?

Some of the therapies to be recently approved for MS include diroximel fumarate (VUMERITY^®), ponesimod (PONVORY™) and ofatumumab (KESIMPTA^®).¹ Diroximel fumarate, while bioequivalent to dimethyl fumarate, is reported to cause less GI irritability since methanol is not one of its byproducts.^2–4 Ponesimod is a selective S1P1 receptor modulator, which decreases and sequesters lymphocytes. It also displays a noteworthy half-life. Ponesimod clinical studies were the first to address fatigue as one of the criteria, but further investigations are needed.^5,6 Ofatumumab is a fully humanised anti-CD20 antibody with a novel binding epitope compared to other drugs in the same class.^7,8 In addition to these new therapies, a change in method of administration for natalizumab (TYSABRI^®) was also discussed.⁹ The previously approved dosage of natalizumab was 300 mg every 4 weeks, for intravenous administration. The new approval allows for subcutaneous administration. Prof. Chan also briefly highlighted the results from the NOVA study, which was presented earlier last year, that addressed dosing every 6 weeks instead of every 4 weeks.¹⁰

Approach to treatment of MS

In recent years, there has been some debate regarding the best approach to treating MS, i.e., whether treatments should follow gradual dose escalation schemes, or if aggressive therapy should be considered from the outset. Prof Chan highlighted the results from the Nordic study, where Denmark had an escalation approach compared to Sweden, which tended to start with highly efficacious DMTs. Results indicated that escalation of treatment efficacy was inferior to using more efficacious DMT as initial treatment.¹¹ This also resulted in an ECTRIMS/EAN guidelines update in 2021.

The elephant in the room: COVID-19 and MS

Prof. Chan briefly alluded to ongoing data from anti-CD20 and S1P receptor modulator treated patients who had received 3 doses of the SARS-CoV2 mRNA vaccine. Preliminary results show a strong antibody response, however he highlighted a potential recruitment bias, as well as the fact that T-cell responses were not being considered.

Do we need more MS therapies?

MS shows different pathomechanisms depending on the stage of the disease which may not always be distinct. Prof. Chan also briefly discussed the phase 3 trials with Bruton’s tyrosine kinase inhibitors on slowly expanding lesions, which are an MRI surrogate of smoldering active demyelinating lesions, which may be driven by microglia.

Prof. Chan concluded that there was certainly a need for more therapies. High heterogeneity in the patient population and targeting variable patho-mechanisms and stages of MS can lead to individual treatment paths in the treatment of MS. He further highlighted that Switzerland has a higher degree of therapeutic freedom. Further information about newly approved therapies in Switzerland can be accessed here.

Read more MS State of the Art Symposium 2022 coverage by following this link.

References

1. Prof. Dr Andrew Chan, ‘Multiple Sclerosis 2022 – How many more therapies do we need?’ Presented at MS State of the Art Symposium, January 31, 2022.
2. Diroxymel fumarate (VUMERITY^®) SmPC, November 2021.
3. Wundes A, et al., Ther Adv Neurol Dis 2021;14: 1–14.
4. Wray S, et al. Poster presented at Joint ACTRIMS-ECTRIMS 2020; P0200.
5. Ponesimod (PONVORY^™) SmPC, last updated June 2021.
6. Kappos L, et al., JAMA Neurol 2021;78(5):558–567.
7. Ofatum (KESIMPTA^®) SmPC, last updated Oct 2021.
8. Hauser SL, et al., New Engl J Med. 2020 6;383(6):546–557.
9. Natalizumab (TYSABRI^®) SmPC, last updated Oct 2021.
10. Foley J, et al., Presented at ECTRIMS 2021; Virtual. P970.
11. Spelman T, et al., JAMA Neurology 2021; 78(10):1197–1204.
12. Montalban X. ECTRIMS/EAN Clinical Guidelines on MS treatment. Presented at ECTRIMS 2021.