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Siponimod

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  1. Summary
  2. Licensing and appraisal
  3. How does siponimod work?
  4. How is siponimod taken?
  5. Siponimod research
  6. Side effects

Other names: BAF312, Mayzent

Summary

Siponimod has been approved as a treatment for active secondary progressive multiple sclerosis (MS). It is taken as a tablet once daily.

Siponimod for secondary progressive MS: Appraisal

  • Siponimod causes lymphocytes to be retained in lymph glands.
  • In secondary progressive MS, siponimod reduced risk of disability progression, compared to placebo.
  • In clinical trials, low white blood cell count, increased liver enzyme levels, slower heart rate when starting treatment, macular oedema (swelling in the back of the eye affecting vision), high blood pressure, shingles, and convulsions occurred more frequently with siponimod than with placebo.

What is Siponimod (Mayzent)

Siponimod is a new drug treatment under investigation for secondary progressive multiple sclerosis (MS). In this video we explore how it works.

Licensing and appraisal

Licensing

The European Commission has granted marketing authorization for siponimod (Mayzent) for the treatment of active secondary progressive MS. This follows a recommendation from the European Medicines Agency that a licence should be granted. Active secondary progressive MS is defined as people experiencing relapses or showing signs of inflammation on MRI scans.

Appraisal

NICE carried out an appraisal of siponimod for secondary progressive MS to decide whether it should be prescribed by the NHS in England and Wales.

In October 2020, NICE approved siponimod for people with secondary progressive MS who continue having relapses or show signs of MS activity on MRI scans.

This announcement reverses NICE's decision earlier this year to reject siponimod. NICE requested more detailed evidence and analysis of the data and is now satisfied that siponimod is cost-effective and can be prescribed by the NHS in England And Wales.

The Scottish Medicines Consortium has approved siponimonid (Mayzent) for people with secondary progressive MS who continue having relapses or show signs of MS activity on MRI scans. The MS Trust also contributed to this appraisal.

In Northern Ireland, the Department of Health reviews NICE guidance for NHS use.

How does siponimod work?

Siponimod belongs to the same class of drugs as Gilenya.

It acts on certain types of white blood cells (lymphocytes) which are involved in the immune attack on myelin seen in MS. It binds to special locations (or receptors) on the surface of the lymphocytes, called sphingosine-1-phosphate receptors (S1P-R). This causes lymphocytes to be retained in the lymph glands. As a result, the number of lymphocytes circulating in the blood and reaching the brain is decreased, resulting in reduced immune attack on nerve cells in the brain and spinal cord.

How is siponimod taken?

Siponimod is taken as a tablet, once daily.

Siponimod research

What are the results so far?

  • BOLD - siponimod compared to placebo in relapsing remitting MS

In a phase II study (BOLD), designed to assess the best dose for reducing MS activity as seen on MRI scans, 188 people with relapsing remitting MS took siponimod for 3 to 6 months. Siponimod reduced the number of brain lesions seen in MRI by up to 80% and reduced relapse rates compared to placebo (0.58 on placebo to 0.2 on 2 mg siponimod).

Results of an extension study in relapsing remitting MS have also been published; MRI-assessed MS activity and relapse rates remained low, particularly in the 1.25, 2 and 10mg treatment groups, with no new safety concerns.

  • EXPAND - siponimod compared to placebo in secondary progressive MS

The phase III EXPAND trial recruited 1651 people with secondary progressive MS. On average, participants had been diagnosed with MS for approximately 17 years, and had had SPMS for about 4 years. Just over half needed walking assistance. Participants took either siponimod (1105) or placebo (546) daily for up to 3 years.

Disability level (EDSS score) was assessed every three months. Disability progression was confirmed if an increase in EDSS was maintained for 3 months.  

Siponimod reduced the risk of 3 month confirmed increase in disability progression by 21% compared to placebo and reduced the risk of 6 month confirmed increase in disability by 26%. 

Further analysis of the study focussed on a subset of participants with "active" SPMS, defined as those who had relapsed in the two years prior to starting the trial or showed MRI evidence of MS activity.

For the active subgroup, siponimod reduced the risk of 3 month confirmed increase in disability progression by 31% compared to placebo and reduced the risk of 6 month confirmed increase in disability by 37%.

Siponimod was also more effective than placebo on other measures used in the study:

  • reduced loss of brain volume
  • reduced MRI-detected brain lesion volume

There was no significant difference between the two groups in the time taken to walk 25 feet.

Side effects

In the phase III EXPAND study, low white blood cell count, increased liver enzyme levels, slower heart rate when starting treatment, macular oedema (swelling in the back of the eye affecting vision), high blood pressure, shingles, and convulsions occurred more frequently with siponimod than with placebo. 

A full list of side effects is included in the manufacturer's Patient Information Leaflet.

Find out more

References

  • Selmaj K, et al. Siponimod for patients with relapsing-remitting multiple sclerosis (BOLD): an adaptive, dose-ranging, randomised, phase 2 study. Lancet Neurology 2013;12(8):756-67. Summary
  • Stuve O, et al. Phase 2 BOLD extension study efficacy results for siponimod (BAF312) in patients with relapsing-remitting multiple sclerosis. Multiple Sclerosis and Related Disorders 2014;3(6):754-5. Summary
  • Kappos L, et al. Safety and Efficacy of Siponimod (BAF312) in Patients With Relapsing-Remitting Multiple Sclerosis: Dose-Blinded, Randomized Extension of the Phase 2 BOLD Study. JAMA Neurology 2016;73(9):1089-1098 Summary
  • Kappos L, et al. Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study Lancet. 2018 Mar 31;391(10127):1263-1273. Summary
  • Gold R, et al. Efficacy of siponimod in secondary progressive multiple sclerosis patients with active disease: the EXPAND study subgroup analysis Mult. Scler. 2019, 25:2_suppl, 357-580, P750. Conference poster

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