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Among patients with multiple sclerosis (MS), relapsing-remitting multiple sclerosis (RRMS) is the most common type.
Among them, up to 50% of RRMS patients develop secondary progressive multiple sclerosis (SPMS) after 10-15 years.
)
.
Compared with RRMS, SPMS is characterized by the continuous progression of the disease, the occurrence of progressive and irreversible neurological dysfunction, which eventually leads to the progressive deterioration of disability
.
Therefore, it is very important for MS patients to start treatment early to slow the progression of the disease.
However, there are not many drugs that can delay the progression of MS disease, and there are fewer drugs that can effectively delay the progression of SPMS disease
.
Sinimod is the first disease modification therapy (DMT) drug approved for patients with active SPMS.
Its phase 3 clinical study-EXPAND study has proven that the drug can effectively delay the progression of SPMS disease and will solve patients with active SPMS Significantly unmet medical needs in the group
.
However, as a new clinical drug, Sinimod is not known about its long-term efficacy and safety
.
Therefore, more studies are urgently needed to confirm the long-term efficacy and safety of Sinimod
.
In response to this, at the 37th European Committee for Multiple Sclerosis Treatment and Research (ECTRIMS 2021) held recently in 2021, the results of 3 extended studies based on the EXPAND study were announced
.
It describes the long-term efficacy of continuous use of Sinimod treatment, the efficacy and safety of treatment of SPMS patients of different ages and Hispanics, thus proving that Sinimod has long-term significant efficacy and has good effects on different SPMS patients.
Efficacy and safety
.
Next, let the editor take everyone to review it
.
Sinimod treatment can continue to delay the progression of disability in SPMS patients for up to 7 years.
The EXPAND study is a global multicenter, event-driven and exposure-driven, double-blind, randomized phase 3 clinical study evaluating the effectiveness and safety of Sinimod.
There is no direct comparison of the long-term efficacy of sinimod and placebo
.
One of the extended studies used the hierarchical structure retention time-to-failure model (RPSFT) to analyze the continuous use of sinimod treatment compared with the model simulated virtual placebo (LTVP) and placebo-to-sinimod treatment (LTPS) groups Patients in the (LTCS) group were based on the 6-month assessment of EDSS to confirm the differences in the risk of disability progression (6mCDP) and the time to progression, and subgroup analysis was performed based on disease activity
.
The purpose is to explore the long-term efficacy of Sinimod compared with a virtual placebo in the 7-year follow-up of the entire SPMS population and the active and inactive subgroups from the core and extended parts of the EXPAND study
.
The results of the study showed that compared with the LTVP group, the risk of 6mCDP in the LTCS group was reduced, and the median time to 6mCDP was delayed, regardless of whether it was in the overall population, active SPMS subgroup or inactive SPMS subgroup.
.
Overall population: Compared with the LTVP group, the 6mCDP risk of the LTCS group was reduced by 33% (p<0.
0001), and the median time of 6mCDP was delayed by 62% (Figure 1a)
.
Figure 1a In the overall population, compared with the LTVP and LTPS groups, the time for the LTCS group to reach 6mCDP Active SPMS population: Compared with the LTVP group, the 6mCDP risk of the LTCS group was reduced by 42% (p<0.
0001), and the median time for 6mCDP Delayed by 79% (Figure 1b)
.
Figure 1b In the active SPMS subgroup, compared with the LTVP and LTPS groups, the LTCS group reached 6mCDP time inactive SPMS population: Compared with the LTVP group, the 6mCDP risk of the LTCS group was reduced by 20% (p=0.
0534), 6mCDP The median time is delayed by 44% (Figure 1c)
.
Figure 1c In the inactive SPMS subgroup, compared with the LTVP and LTPS groups, the time to reach 6mCDP in the LTCS group* represents a statistically significant difference at the 0.
05 level (two-sided)
.
6mCDP: confirmation of disability progression within 6 months; CI: confidence interval; HR: hazard ratio; ITT: intention to treat; LTCS: long-term continuous sinimod treatment; LTPS: long-term placebo-sinimod treatment (ITT analysis-not Modeling); LTVP: long-term simulated virtual placebo treatment; RPSFT: hierarchical structure retention time-to-failure model; SPMS: secondary progressive multiple sclerosis , Continuous use of Sinimod treatment for up to 7 years, can continue to significantly reduce the risk of disability progression and delay the 6mCDP time
.
Among them, in the active SPMS subgroup, sinimod has a more obvious effect on the progression of disability and has a better curative effect
.
The above-mentioned studies provide strong evidence-based support for the long-term efficacy of sinimod treatment, so are its efficacy and safety for patients of different age groups and other ethnic groups consistent with the overall population? Sinimod has good efficacy and safety in treating patients with active SPMS of different ages.
At present, for patients with relapsing multiple sclerosis (RMS), although there are treatment options, the risk of converting to SPMS is still high
.
SPMS is characterized by progressive and irreversible neurological dysfunction
.
Increasing age may be related to the cumulative risk of disability, not to the duration of MS, and may have a negative impact on treatment outcomes
.
Another extended study analyzed data from subgroups of patients with a baseline age of <50 years and ≥50 years in the EXPAND study, aiming to evaluate the efficacy and safety of sinimod in the treatment of patients with active SPMS
.
The results of the study showed that compared with placebo, sinimod generally reduced CDP at 3 and 6 months in patients with active SPMS, whether in the overall population or in subgroups aged <50 or ≥50 years of age.
Risk
.
Sinimod has good safety in both age subgroups
.
And in the two subgroups of different ages, the incidence of serious adverse events (AE) in the sinimod group was slightly lower than that in the placebo group (Figure 2)
.
Figure 2 The incidence of AEs in the overall EXPAND population and the baseline age subgroup.
This study shows that Sinimod provides clinical benefits in reducing the risk of CDP in patients with active SPMS at different ages
.
And the safety of Sinimod in patients with active SPMS is generally good
.
These results are consistent with the overall active SPMS cohort in the EXPAND study
.
Sinimod also has good efficacy and safety in the treatment of Hispanic SPMS patients.
At present, due to the continuous under-representation of minority groups in clinical trials, the data needed for decision-making in minority groups are limited.
Therefore, more clinical evidence is urgently needed
.
The last extended study analyzed the efficacy and safety of a group of Hispanic patients with active SPMS from the EXPAND study on the efficacy and safety of 2 mg sinimod daily
.
The results of the study showed that compared with placebo, the 3-month CDP risk of patients treated with sinimod was reduced by 42%, and the 6-month CDP risk was reduced by 67% (Figure 3)
.
Figure 3 CDP time of 3 months and 6 months and the safety of Sinimod is generally good
.
The incidence of AEs, SAEs, and AEs that led to discontinuation was similar between the treatment groups (Table 1)
.
Table 1 The incidence of adverse events.
In summary, among the Hispanic active SPMS patients treated with Sinimod, the CDP risk was numerically reduced, and the safety profile was generally good, which is similar to the overall active SPMS cohort observed in EXPAND The results are consistent
.
Summary The long-term efficacy and safety of therapeutic drugs have always been issues of concern to clinicians.
The above-mentioned EXPAND extended studies have confirmed that continuous use of sinimod therapy can significantly reduce the risk of 6mCDP, significantly delay the progression time, and continue to have a longer effect.
Up to 7 years, and has good efficacy and safety for patients of all age groups and different ethnic groups
.
Sinimod, as the world's first and only oral DMT drug with large-scale clinical trials to prove its efficacy in SPMS patients, has brought clinicians a new weapon in the treatment of MS
.
The above research results also provide evidence-based evidence support for Sinimod to effectively treat MS and benefit patients in the long-term
.
It is believed that in the future, this new weapon will be better promoted and applied, thereby enhancing the treatment level of MS and improving the prognosis of MS patients
.
References: 1.
Bruce AC Cree, et al.
Estimating Long-Term Effect of Siponimod on Disability Progression versus Virtual Placebo in SPMS Using RPSFT Model: EXPAND Data Up to 7 Years.
ECTRIMS 2021.
2.
LH Hua, et al.
Analyses of the effect of baseline age on the efficacy and safety of siponimod in patients with active secondary progressive multiple sclerosis from the EXPAND study.
ECTRIMS 2021.
3.
S.
Cohan, et al.
Safety and efficacy of siponimod in patients with active secondary progressive multiple sclerosis identifying as Hispanic from the phase 3 EXPAND study.
ECTRIMS 2021.
Among them, up to 50% of RRMS patients develop secondary progressive multiple sclerosis (SPMS) after 10-15 years.
)
.
Compared with RRMS, SPMS is characterized by the continuous progression of the disease, the occurrence of progressive and irreversible neurological dysfunction, which eventually leads to the progressive deterioration of disability
.
Therefore, it is very important for MS patients to start treatment early to slow the progression of the disease.
However, there are not many drugs that can delay the progression of MS disease, and there are fewer drugs that can effectively delay the progression of SPMS disease
.
Sinimod is the first disease modification therapy (DMT) drug approved for patients with active SPMS.
Its phase 3 clinical study-EXPAND study has proven that the drug can effectively delay the progression of SPMS disease and will solve patients with active SPMS Significantly unmet medical needs in the group
.
However, as a new clinical drug, Sinimod is not known about its long-term efficacy and safety
.
Therefore, more studies are urgently needed to confirm the long-term efficacy and safety of Sinimod
.
In response to this, at the 37th European Committee for Multiple Sclerosis Treatment and Research (ECTRIMS 2021) held recently in 2021, the results of 3 extended studies based on the EXPAND study were announced
.
It describes the long-term efficacy of continuous use of Sinimod treatment, the efficacy and safety of treatment of SPMS patients of different ages and Hispanics, thus proving that Sinimod has long-term significant efficacy and has good effects on different SPMS patients.
Efficacy and safety
.
Next, let the editor take everyone to review it
.
Sinimod treatment can continue to delay the progression of disability in SPMS patients for up to 7 years.
The EXPAND study is a global multicenter, event-driven and exposure-driven, double-blind, randomized phase 3 clinical study evaluating the effectiveness and safety of Sinimod.
There is no direct comparison of the long-term efficacy of sinimod and placebo
.
One of the extended studies used the hierarchical structure retention time-to-failure model (RPSFT) to analyze the continuous use of sinimod treatment compared with the model simulated virtual placebo (LTVP) and placebo-to-sinimod treatment (LTPS) groups Patients in the (LTCS) group were based on the 6-month assessment of EDSS to confirm the differences in the risk of disability progression (6mCDP) and the time to progression, and subgroup analysis was performed based on disease activity
.
The purpose is to explore the long-term efficacy of Sinimod compared with a virtual placebo in the 7-year follow-up of the entire SPMS population and the active and inactive subgroups from the core and extended parts of the EXPAND study
.
The results of the study showed that compared with the LTVP group, the risk of 6mCDP in the LTCS group was reduced, and the median time to 6mCDP was delayed, regardless of whether it was in the overall population, active SPMS subgroup or inactive SPMS subgroup.
.
Overall population: Compared with the LTVP group, the 6mCDP risk of the LTCS group was reduced by 33% (p<0.
0001), and the median time of 6mCDP was delayed by 62% (Figure 1a)
.
Figure 1a In the overall population, compared with the LTVP and LTPS groups, the time for the LTCS group to reach 6mCDP Active SPMS population: Compared with the LTVP group, the 6mCDP risk of the LTCS group was reduced by 42% (p<0.
0001), and the median time for 6mCDP Delayed by 79% (Figure 1b)
.
Figure 1b In the active SPMS subgroup, compared with the LTVP and LTPS groups, the LTCS group reached 6mCDP time inactive SPMS population: Compared with the LTVP group, the 6mCDP risk of the LTCS group was reduced by 20% (p=0.
0534), 6mCDP The median time is delayed by 44% (Figure 1c)
.
Figure 1c In the inactive SPMS subgroup, compared with the LTVP and LTPS groups, the time to reach 6mCDP in the LTCS group* represents a statistically significant difference at the 0.
05 level (two-sided)
.
6mCDP: confirmation of disability progression within 6 months; CI: confidence interval; HR: hazard ratio; ITT: intention to treat; LTCS: long-term continuous sinimod treatment; LTPS: long-term placebo-sinimod treatment (ITT analysis-not Modeling); LTVP: long-term simulated virtual placebo treatment; RPSFT: hierarchical structure retention time-to-failure model; SPMS: secondary progressive multiple sclerosis , Continuous use of Sinimod treatment for up to 7 years, can continue to significantly reduce the risk of disability progression and delay the 6mCDP time
.
Among them, in the active SPMS subgroup, sinimod has a more obvious effect on the progression of disability and has a better curative effect
.
The above-mentioned studies provide strong evidence-based support for the long-term efficacy of sinimod treatment, so are its efficacy and safety for patients of different age groups and other ethnic groups consistent with the overall population? Sinimod has good efficacy and safety in treating patients with active SPMS of different ages.
At present, for patients with relapsing multiple sclerosis (RMS), although there are treatment options, the risk of converting to SPMS is still high
.
SPMS is characterized by progressive and irreversible neurological dysfunction
.
Increasing age may be related to the cumulative risk of disability, not to the duration of MS, and may have a negative impact on treatment outcomes
.
Another extended study analyzed data from subgroups of patients with a baseline age of <50 years and ≥50 years in the EXPAND study, aiming to evaluate the efficacy and safety of sinimod in the treatment of patients with active SPMS
.
The results of the study showed that compared with placebo, sinimod generally reduced CDP at 3 and 6 months in patients with active SPMS, whether in the overall population or in subgroups aged <50 or ≥50 years of age.
Risk
.
Sinimod has good safety in both age subgroups
.
And in the two subgroups of different ages, the incidence of serious adverse events (AE) in the sinimod group was slightly lower than that in the placebo group (Figure 2)
.
Figure 2 The incidence of AEs in the overall EXPAND population and the baseline age subgroup.
This study shows that Sinimod provides clinical benefits in reducing the risk of CDP in patients with active SPMS at different ages
.
And the safety of Sinimod in patients with active SPMS is generally good
.
These results are consistent with the overall active SPMS cohort in the EXPAND study
.
Sinimod also has good efficacy and safety in the treatment of Hispanic SPMS patients.
At present, due to the continuous under-representation of minority groups in clinical trials, the data needed for decision-making in minority groups are limited.
Therefore, more clinical evidence is urgently needed
.
The last extended study analyzed the efficacy and safety of a group of Hispanic patients with active SPMS from the EXPAND study on the efficacy and safety of 2 mg sinimod daily
.
The results of the study showed that compared with placebo, the 3-month CDP risk of patients treated with sinimod was reduced by 42%, and the 6-month CDP risk was reduced by 67% (Figure 3)
.
Figure 3 CDP time of 3 months and 6 months and the safety of Sinimod is generally good
.
The incidence of AEs, SAEs, and AEs that led to discontinuation was similar between the treatment groups (Table 1)
.
Table 1 The incidence of adverse events.
In summary, among the Hispanic active SPMS patients treated with Sinimod, the CDP risk was numerically reduced, and the safety profile was generally good, which is similar to the overall active SPMS cohort observed in EXPAND The results are consistent
.
Summary The long-term efficacy and safety of therapeutic drugs have always been issues of concern to clinicians.
The above-mentioned EXPAND extended studies have confirmed that continuous use of sinimod therapy can significantly reduce the risk of 6mCDP, significantly delay the progression time, and continue to have a longer effect.
Up to 7 years, and has good efficacy and safety for patients of all age groups and different ethnic groups
.
Sinimod, as the world's first and only oral DMT drug with large-scale clinical trials to prove its efficacy in SPMS patients, has brought clinicians a new weapon in the treatment of MS
.
The above research results also provide evidence-based evidence support for Sinimod to effectively treat MS and benefit patients in the long-term
.
It is believed that in the future, this new weapon will be better promoted and applied, thereby enhancing the treatment level of MS and improving the prognosis of MS patients
.
References: 1.
Bruce AC Cree, et al.
Estimating Long-Term Effect of Siponimod on Disability Progression versus Virtual Placebo in SPMS Using RPSFT Model: EXPAND Data Up to 7 Years.
ECTRIMS 2021.
2.
LH Hua, et al.
Analyses of the effect of baseline age on the efficacy and safety of siponimod in patients with active secondary progressive multiple sclerosis from the EXPAND study.
ECTRIMS 2021.
3.
S.
Cohan, et al.
Safety and efficacy of siponimod in patients with active secondary progressive multiple sclerosis identifying as Hispanic from the phase 3 EXPAND study.
ECTRIMS 2021.
