Prescribing information

 

The efficacy profile of MAYZENT was characterised in the EXPAND study and exploratory post-hoc analyses.

MAYZENT demonstrated efficacy in a range of MS outcome measures1–5

Image showing the outcome measures evaluated in the EXPAND study: acute disease activity, T2 lesion load, cognitive processing speed, confirmed disability progression, and brain volume lossAcute disease activity  T2 lesion load  Cognitive processing speed  Confirmed disability progression  Brain volume loss 

 Icon for confirmed disability progression

MAYZENT impact on disability progression outcomes

MAYZENT was proven to slow progression in SPMS patients with active disease.5,6*

Charts showing time to 3-month confirmed disability progression over 42 months, and time to 6-month confirmed diasbility progression in patients with active disease

The EXPAND trial was a randomised, double-blind, placebo-controlled, phase III study of 1651 patients with SPMS over 24 months, followed by an optional open-label extension.1

*In a subgroup analysis in EXPAND, SPMS with active disease was defined as patients with relapse in the 2 years prior to the study and/or presence of Gd-enhancing T1 lesions at baseline.5
Time to 3-month CDP was defined as a ≥1-point increase from baseline in EDSS score (0.5-point increase for patients with a baseline EDSS score of ≥5.5), sustained for 3 months.1
Time to 6-month CDP was defined as a ≥1-point increase from baseline in EDSS score (0.5-point increase for patients with a baseline EDSS score of ≥5.5), sustained for 6 months.1

CDP, confirmed disability progression; CI, confidence interval; EDSS, Expanded Disability Status Scale; Gd, gadolinium; HR, hazard ratio; SPMS, secondary progressive multiple sclerosis.

 

MAYZENT demonstrated long-term efficacy on delaying 6-month CDP in SPMS patient with active disease*7

long-term-efficacy-in-delaying-6-month-cdp-in-spms-patients-with-active-disease

*Post hoc subgroup analysis (ITT population) of the core and extension parts of the Phase III EXPAND study, which included 779 patients with SPMS with active disease who had received ≥1 dose of randomised treatment during the core study and who were followed in the extension analysis: continuous MAYZENT (n=516) and placebo-MAYZENT (n=263) groups for 53.8 months (median).7
The EXPAND trial was a randomised, double-blind, placebo-controlled, Phase III study of 1651 patients with SPMS over 24 months, followed by an optional open-label extension.1
Average delay of 72% across the 25th to 40th percentile.7

CDP, confirmed disability progression; CI, confidence interval; HR, hazard ratio; ITT, intention to treat population; SPMS, secondary progressive multiple sclerosis.

 Infographic showing time to 3-month diasbiltiy progression, 6-month diasability progression and progression to wheelchair dependence in total study population.

Although the EXPAND study was in a broad SPMS population, MAYZENT is indicated for the treatment of adult patients with SPMS with active disease evidenced by relapses or imaging features of inflammatory activity.

*Time to 3-month CDP was defined as a ≥1-point increase from baseline in EDSS score (0.5-point increase for patients with a baseline EDSS score of ≥5.5), sustained for 3 months.1
Time to 6-month CDP was defined as a ≥1-point increase from baseline in EDSS score (0.5-point increase for patients with a baseline EDSS score of ≥5.5), sustained for 6 months.1

CDP, confirmed disability progression; CI, confidence interval; EDSS, Expanded Disability Status Scale; SPMS, secondary progressive multiple sclerosis.

 

MAYZENT demonstrated a benefit on 6-month CDP for up to 5 years in the total patient population9

*Although the EXPAND study was in a broad SPMS population, MAYZENT is indicated for the treatment of adult patients with secondary progressive multiple sclerosis (SPMS) with active disease evidenced by relapses or imaging features of inflammatory activity.1,6 The EXPAND trial was a randomised, double-blind, placebo-controlled, Phase III study of 1651 patients with SPMS over 24 months, followed by an optional open-label extension.1
The average time to reach 6-month CDP was 49.3% across the 25th and 40th percentiles as MAYZENT did not reach the median.9

CDP, confirmed disability progression; CI, confidence interval; HR, hazard ratio; ITT, intention to treat population.

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 Icon for brain volume loss

MAYZENT impact on grey matter atrophy

 

MAYZENT significantly reduced cortical grey matter and thalamic atrophy in SPMS patients with active disease10

*Post-hoc subgroup analysis (PPS population) of the Phase III EXPAND study, which included 521 patients with SPMS with active disease.10 The EXPAND trial was a randomised, double-blind, placebo-controlled, Phase III study of 1651 patients with SPMS over 24 months, followed by an optional open-label extension.1

cGM, cortical grey matter; PPS, per protocol set.

MAYZENT reduced grey matter in the total patient population*1,11

*Although the EXPAND study was in a broad SPMS population, MAYZENT is indicated for the treatment of adult patients with secondary progressive multiple sclerosis (SPMS) with active disease evidenced by relapses or imaging features of inflammatory activity.1,6 The EXPAND trial was a randomised, double-blind, placebo-controlled, Phase III study of 1651 patients with SPMS over 24 months, followed by an optional open-label extension.1

PPS, per protocol set.

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Icon for cognitive processing speed

MAYZENT impact on cognitive decline

MAYZENT sustained a benefit in CPS for up to 5 years in SPMS patients with active disease*5,7

MAYZENT sustained a benefit in CPS for up to 5 years in SPMS patients with active disease*5,7

*Post hoc subgroup analysis (ITT population) of the core and extension parts of the Phase III EXPAND study, which included 779 patients with SPMS with active disease who had received ≥1 dose of randomised treatment during the core study and who were followed in the extension analysis: continuous MAYZENT (n=516) and placebo-MAYZENT (n=263) groups for 53.8 months (median).7 The EXPAND trial was a randomised, double-blind, placebo-controlled, Phase III study of 1651 patients with SPMS over 24 months, followed by an optional open-label extension.1
Data presented as published. Absolute numbers unavailable.
Decline in CPS was assessed by a 4-point worsening on the SDMT.7
§Time to 6-month confirmed cognitive worsening (6-month CPS; CCW) was based on a clinically, meaningful worsening in CPS defined as a ≥4-point decline in the SDMT score.7
||The average time to reach 6-month confirmed worsening of CPS was 73% across the 25th and 30th percentile as MAYZENT did not reach the median.7

CI, confidence interval; CPS, cognitive processing speed; HR, hazard ratio; ITT, intention to treat; SDMT, Symbol Digit Modalities Test; SPMS, secondary progressive multiple sclerosis.

MAYZENT sustained a benefit in CPS for up to 5 years in the total population*6,9

Infographic showing MAYZENT sustained a benefit in CPS for up to 5 years in the total population*6,9

*Although the EXPAND study was in a broad SPMS population, MAYZENT is indicated for the treatment of adult patients with secondary progressive multiple sclerosis (SPMS) with active disease evidenced by relapses or imaging features of inflammatory activity.1,6 The EXPAND trial was a randomised, double-blind, placebo-controlled, Phase III study of 1651 patients with SPMS over 24 months, followed by an optional open-label extension.1
Decline in CPS was assessed by a 4-point worsening on the SDMT.9
Data presented as published. Absolute numbers unavailable.
Time to 6-month confirmed cognitive worsening was based on a clinically, meaningful worsening in CPS defined as a ≥4-point decline in the SDMT score.9
§The average time to reach 6-month confirmed worsening of CPS was 55% across the 25th and 30th percentiles as MAYZENT did not reach the median.9

CI, confidence interval; CPS, cognitive processing speed; HR, hazard ratio; SDMT, Symbol Digit Modalities Test; SPMS, secondary progressive multiple sclerosis.

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 Icon for acute disease activity

MAYZENT impact on disease activity

MAYZENT demonstrated up to 5 years of consistent reductions in ARR in SPMS patients with active disease*6,7

*Post hoc subgroup analysis (ITT population) of the core and extension parts of the Phase III EXPAND study, which included 779 patients with SPMS with active disease who had received ≥1 dose of randomised treatment during the core study and who were followed in the extension analysis: continuous MAYZENT (n=516) and placebo-MAYZENT (n=263) groups for 53.8 months (median).7 The EXPAND trial was a randomised, double-blind, placebo-controlled, Phase III study with a broad SPMS patient population of 1651 over 24 months, followed by an optional open-label extension.1
Data presented as published. Absolute numbers unavailable.
Negative binomial regression model adjusted for the core treatment group.7
§Within-group comparison between placebo (core) and placebo-MAYZENT (extension). The rate ratios were 0.15 (95% CI: 0.11, 0.21) and 0.04 (95% CI: 0.03, 0.07), respectively.7 
||Within-group comparison between the continuous MAYZENT (extension) and MAYZENT (core). The rate ratios were 0.06 (95% CI: 0.04, 0.08) and 0.11 (95% CI: 0.08, 0.14), respectively.7

ARR, annualised relapse rate; CI, confidence interval; SPMS, secondary progressive multiple sclerosis.

MAYZENT demonstrated up to 5 years of consistent reductions in ARR in the total patient population*9

Graph detailing MAYZENT demonstrated up to 5 years of consistent reductions in ARR in the total patient population*9

*Although the EXPAND study was in a broad SPMS population, MAYZENT is indicated for the treatment of adult patients with secondary progressive multiple sclerosis (SPMS) with active disease evidenced by relapses or imaging features of inflammatory activity.1,6 The EXPAND trial was a randomised, double-blind, placebo-controlled, Phase III study of 1651 patients with SPMS over 24 months, followed by an optional open-label extension.1
The rate ratio was 0.48 (95% CI: 0.37, 0.62).9
Negative binomial regression model adjusted for the core treatment group.9
§Within-group comparison between placebo (core) and placebo-MAYZENT (extension). The rate ratio was 0.37 (95% CI: 0.24, 0.58).9
||Within-group comparison between the continuous MAYZENT (extension) and MAYZENT (core). The rate ratio was 0.58 (95% CI: 0.44, 0.77).9
Early/earlier treatment refers to patients who were on MAYZENT in the core study; later treatment refers to the placebo-switch group in the extension study.

ARR, annualised relapse rate; CI, confidence interval; ITT, intention to treat.

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 Icon for T2 lesion load.

MAYZENT impact on T2 lesion loads

MAYZENT had a significant effect on T2 lesion loads in SPMS patients with active disease*

 Infographic showing reduction in new or enlarging T2 lesions in patients with active disease

*In a subgroup analysis in EXPAND, SPMS with active disease was defined as patients with relapse in the 2 years prior to the study and/or presence of Gd-enhancing T1 lesions at baseline.1

CI, confidence interval; SPMS, secondary progressive multiple sclerosis.

MAYZENT had a significant effect on T2 lesion loads in the total patient population

 Infographic showing reductions T2 lesion volume, and in new or enlarging T2 lesions in the total patient population

Although the EXPAND study was in a broad SPMS population, MAYZENT is indicated for the treatment of adult patients with SPMS with active disease evidenced by relapses or imaging features of inflammatory activity.

Adjusted mean over months 12 and 24, with 184 mm2 for MAYZENT compared with 879 mm2 for placebo (P<0.0001).1
0.7 (mean for MAYZENT) compared with 3.6 (mean for placebo) (P<0.0001).1

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Indication: MAYZENT is indicated for the treatment of adult patients with SPMS with active disease evidenced by relapses or imaging features of inflammatory activity.6

SPMS, secondary progressive multiple sclerosis.

References

  1. Kappos L et al. Lancet. 2018;391(10127):1263‒1273 and supplementary material.
  2. Ziemssen T et al. J Neurol. 2016;263(6):1053–1065.
  3. Benedict RHB et al. Impact of siponimod on cognition in patients with secondary progressive multiple sclerosis: results from the phase 3 EXPAND study. Poster presented at: AAN Meeting; 26 April 2018; Los Angeles, CA, USA
  4. Galboiz Y et al. Curr Opin Neurol. 2002;15(3):233–237.
  5. Gold R et al. Efficacy of siponimod in secondary progressive multiple sclerosis patients with active disease: the EXPAND study subgroup analysis. Poster P750 presented at: the 35th ECTRIMS Congress; 11–13 September 2019; Stockholm, Sweden.
  6. MAYZENT (siponimod) Summary of Product Characteristics.
  7. Giovannoni G et al. Sustained reduction of disability and cognitive decline with long-term siponimod treatment in patients with active SPMS: EXPAND data up to 5 years. Poster presented at: the joint 8th ACTRIMS/ECTRIMS Congress; 11–13 September 2020; Virtual. 
  8. Vermersch P et al. Siponimod delays the time to wheelchair in patients with SPMS: results from the EXPAND study. Presented at: the 35th ECTRIMS Congress; 11–13 September 2019; Stockholm, Sweden.
  9. Kappos L, et al. Long-term efficacy and safety of Siponimod in patients with SPMS: EXPAND extension analysis up to 5 years. Poster presented at 72nd Congress of the American Academy of Neurology; April 25–May 1, 2020; Virtual.
  10. Fox RJ et al. Siponimod reduces grey matter atrophy in patients with secondary progressive multiple sclerosis: subgroup analyses from the EXPAND study. Poster presented at: 72nd Congress of the American Academy of Neurology; April 25–May 1, 2020; Virtual. 
  11. Arnold DL, et al. Effect of siponimod on cortical grey matter and thalamic volume in patients with secondary progressive multiple sclerosis - results of the EXPAND study. Poster P382 presented at: the 35th ECTRIMS Congress and 24th Annual Conference of Rehabilitation in MS; 11–13 September 2019; Stockholm, Sweden.
  12. Paz Soldan MM et al. Neurology. 2015;84(1):81–88.
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