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Ponesimod

Phase 3

Multiple Sclerosis | Small molecule | Immunology |Johnson & Johnson|Last Updated: Jun 22, 2025

Success Probability
Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
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Market & Valuation
rNPV $3.2B
Market Size $9.4B
Revenue Basis $1.6B
Competitors 6
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Trial Design
RandomizedDouble-BlindCONTROLLEDDMCBiomarker
Total Trials3
Total Enrollment2,363
FDA Designations
No designations recorded
Clinical Trials (3)
NCT IDTitlePhaseStatusEnrollmentVelocityDesignStartCompletionLast UpdatedSitesCountries
NCT03232073Long-term Extension to Study AC-058B301 to Investigate Safety, Tolerability and Disease Control of Ponesimod 20 mg in Patients With Relapsing Multiple SclerosisPHASE3 COMPLETED 877Jul 5, 2017Jan 16, 2024Jun 22, 2025148 United States, Belarus +26
NCT02425644Oral Ponesimod Versus Teriflunomide In Relapsing MUltiple SclerosisPHASE3 COMPLETED 1,133Jun 4, 2015May 16, 2019Mar 30, 2025162 United States, Belarus +26
NCT01093326Clinical Study to Investigate the Long-term Safety, Tolerability, and Efficacy of Ponesimod in Patients With Relapsing-remitting Multiple SclerosisPHASE2 COMPLETED 353May 12, 2010Sep 6, 2023Mar 30, 202571 United States, Austria +18
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Study Endpoints
Primary Endpoints
Annualized Confirmed Relapse Rate (ARR)
From randomization in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months

ARR: number of confirmed relapses per patient-year. Relapse: new, worsening, or recurrent neurological symptoms that occurred at least 30 days after the onset of a preceding relapse, and that lasted at least 24 hours, in the absence of fever or infection. A confirmed relapse is identified when a patient's symptoms worsen as indicated by an increase in their Expanded Disability Status Scale (EDSS) or Functional Systems (FS) scores, consistent with previous clinically stable assessments. Specific criteria for a confirmed relapse include: An increase of 0.5 points on EDSS; (unless EDSS=0, then requires an increase of 1.0-point); An increase of at least 1.0 point in at least two FS scores; or a 2.0-point increase in one FS score (excluding bladder/bowel and cerebral). Rating individual FS scores is used to rate EDSS along with observations and information concerning gait and use of assistance. EDSS is ordinal clinical rating scale ranging:0 (normal)-10 (death due to MS).

Time From Core Study Randomization to First Confirmed Relapse
From randomization in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months

Time to first confirmed relapse: date of first confirmed relapse (in either core or extension study) minus date of randomization in core study+1 day. Relapse: new, worsening, or recurrent neurological symptoms that occurred at least 30 days after the onset of a preceding relapse, and that lasted at least 24 hours in absence of fever or infection. A confirmed relapse: when patient's symptoms worsen as indicated by an increase in their EDSS/FS scores, consistent with previous clinically stable assessments. Specific criteria for confirmed relapse are: An increase of 0.5 points on EDSS; (unless EDSS=0, then requires an increase of 1.0-point); An increase of at least 1.0 point in at least two FS scores; or a 2.0-point increase in one FS score (excluding bladder/bowel and cerebral). Rating individual FS scores is used to rate EDSS along with observations and information concerning gait and use of assistance. EDSS is ordinal clinical rating scale ranging:0(normal)-10(death due to MS).

Time to First 12-week Confirmed Disability Accumulation (CDA)
From baseline in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months

Time to first 12-week CDA is defined as start date of the first 12-week CDA minus date of randomization in the core study + 1 day. A 12-week CDA is defined as a 12-week sustained increase from the core baseline EDSS score, which is confirmed at a scheduled visit after 12-weeks. CDA is defined as: (a) Sustained increase of at least 1.5 in EDSS for participants with a core baseline EDSS score of 0; (b) Sustained increase of at least 1.0 in EDSS for participants with a core baseline EDSS score of 1.0 to 5.0; (c) Sustained increase of at least 0.5 in EDSS for participants with a core baseline EDSS score \>=5.5, confirmed after 12 weeks. EDSS is an ordinal clinical rating scale ranging from 0 (normal neurological examination) to 10 (death due to MS). Core baseline for efficacy: last non-missing value recorded before or on randomization in the core study for each outcome measure and participant individually.

Time to First 24-week Confirmed Disability Accumulation (CDA)
From baseline in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months

Time to first 24-week CDA was defined as start date of the first 24-week CDA minus date of randomization in the core study + 1 day. A 24-week CDA was defined as a 24-week sustained increase from the core baseline EDSS score, which is confirmed at a scheduled visit after 24-weeks. CDA was defined as: (a) Sustained increase of at least 1.5 in EDSS for participants with a core baseline EDSS score of 0; (b) Sustained increase of at least 1.0 in EDSS for participants with a core baseline EDSS score of 1.0 to 5.0; (c) Sustained increase of at least 0.5 in EDSS for participants with a core baseline EDSS score \>=5.5, confirmed after 24 weeks. EDSS was an ordinal clinical rating scale ranging from 0 (normal neurological examination) to 10 (death due to MS). Core baseline for efficacy: last non-missing value recorded before or on randomization in the core study for each outcome measure and participant individually.

Percentage of Participants With Absence of Relapses
From baseline in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months

Relapse: new, worsening, or recurrent neurological symptoms that occurred at least 30 days after the onset of a preceding relapse, and that lasted at least 24 hours in absence of fever or infection. A confirmed relapse: when patient's symptoms worsen as indicated by an increase in their EDSS/FS scores, consistent with previous clinically stable assessments. Specific criteria for confirmed relapse: An increase of 0.5 points on EDSS; (unless EDSS=0, then requires an increase of 1.0-point); An increase of at least 1.0 point in at least two FS scores; or a 2.0-point increase in one FS score (excluding bladder/bowel and cerebral). Rating individual FS scores is used to rate EDSS along with observations and information concerning gait and use of assistance. EDSS is ordinal clinical rating scale ranging:0(normal)-10(death due to MS). Core baseline for efficacy: last non-missing value recorded before or on randomization in the core study for each outcome measure and participant individually.

Change From Baseline in Expanded Disability Status Scale (EDSS)
From baseline in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months

EDSS is ordinal clinical rating scale based on standard neurological examination for assessing neurological disability and impairment in MS. Seven FS scores were rated on a scale ranged from 0 to 5 or 6 to assess visual, brain, stem, pyramidal, cerebellar, sensory, bowel and bladder, and cerebral functions while ambulation was scored on scale ranged from 0 to 12 to assess walking distance and assistance. Individual FS scores were then used in conjugation with ambulation score to obtain EDSS score which ranged from 0 (normal) to 10 (death due to MS) in 0.5 unit increments that represented higher levels of disability. Core baseline for efficacy is defined as the last non-missing value recorded before or on randomization in the core study for each outcome measure and each participant individually.

Percentage of Participants With No Evidence of Disease Activity (NEDA) Status According to NEDA With Three Components (NEDA-3) at Extension End of Study
From baseline in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months

NEDA-3 up to extension EOS is defined by the absence of confirmed relapse, gadolinium-enhancing (Gd+ T1) lesions, new or enlarging T2 lesions, and 12-week CDA. If at least one of the criteria was not fulfilled or the participant discontinued treatment prematurely, the participant was not considered to have achieved NEDA-3. Confirmed relapse: when patient's symptoms worsen as indicated by an increase in their EDSS/FS scores, consistent with previous clinically stable assessments. Rating individual FS scores is used to rate EDSS along with observations and information concerning gait and use of assistance. EDSS is ordinal clinical rating scale ranging: 0 (normal)-10 (death due to MS). Core baseline for efficacy is defined as the last non-missing value recorded before or on randomization in the core study for each outcome measure and each participant individually.

Percentage of Participants With No Evidence of Disease Activity (NEDA) Status According to NEDA With Four Components (NEDA-4) at Extension End of Study
From baseline in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months

NEDA-4 up to EOS is defined by the absence of confirmed relapse, Gd+ T1 lesions, new or enlarging T2 lesions, 12-week CDA until EOS, and absence of annual brain volume decrease \>=0.4% from core baseline up to extension EOS. If at least one of the criteria was not fulfilled or the participant discontinued treatment prematurely, the participant was not considered to have achieved NEDA-4. Confirmed relapse: when patient's symptoms worsen by an increase in their EDSS/FS scores, consistent with previous clinically stable assessments. Rating individual FS scores is used to rate EDSS along with observations and information concerning gait and use of assistance. EDSS is ordinal clinical rating scale ranging: 0 (normal)-10 (death due to MS). Core baseline for efficacy is defined as the last non-missing value recorded before or on randomization in core study for each outcome measure and each participant individually.

Percent Change From Baseline in Brain Volume (PCBV) Measured by Magnetic Resonance Imaging (MRI)
From baseline in the core study up to the end of treatment (EOT) in the extension study. The actual time varied for each participant and could be up to 94.8 months

Percent change from baseline in brain volume (PCBV) measured by MRI were reported. Normalized Brain Volume at core baseline was measured in cubic centimeter (cm\^3). Core baseline for efficacy is defined as the last non-missing value recorded before or on randomization in the core study for each outcome measure and each participant individually. In this outcome measure, results were presented for extension end of treatment visit.

Cumulative Number of Combined Unique Active Lesions (CUAL) Measured by MRI
From baseline in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months

CUALs was calculated as sum of new T1 Gadolinium-enhanced (Gd+) lesions and new or enlarging T2 lesions (without double-counting of lesions) from baseline up to extension EOS based on the Magnetic resonance imaging (MRI). Average number of lesions per patient-year were reported. Results are based on a negative-binomial regression model. Core baseline for efficacy is defined as the last non-missing value recorded before or on randomization in the core study for each outcome measure and each participant individually.

Number of Gadolinium-enhancing (Gd+) T1 Lesions Measured by MRI
From baseline in the core study up to the end of treatment (EOT) in the extension study. The actual time varied for each participant and could be up to 94.8 months

Number of Gd+ T1 lesions measured by MRI were reported. Results are based on a negative-binomial regression model. Core baseline for efficacy is defined as the last non-missing value recorded before or on randomization in the core study for each outcome measure and each participant individually. For this outcome measure, results presented here are for the Extension end-of-treatment visit.

Cumulative Number of New or Enlarging T2 Lesions Measured by MRI
From baseline in the core study up to the end of study (EOS) in the extension study. The actual time varied for each participant and could be up to 98.5 months

Cumulative number of new or enlarging T2 lesions measured by MRI were reported. Average number of lesions per year were reported. Results are based on a negative-binomial regression model. Core baseline for efficacy is defined as the last non-missing value recorded before or on randomization in the core study for each outcome measure and each participant individually.

Change From Baseline in Volume of MRI Lesions (T2 Lesions and T1 Hypointense Lesions)
From baseline in the core study up to the end of treatment (EOT) in the extension study. The actual time varied for each participant and could be up to 94.8 months

Change from baseline in volume of MRI lesions (T2 lesions, T1 hypointense lesions) were reported. Core baseline for efficacy is defined as the last non-missing value recorded before or on randomization in the core study for each outcome measure and each participant individually. In this outcome measure, results were presented for extension end of treatment visit.

Number of Participants With Absence of MRI Lesions (Gd+ T1 Lesions, New or Enlarging T2 Lesions)
From baseline in the core study up to the end of treatment (EOT) in the extension study. The actual time varied for each participant and could be up to 94.8 months

Number of participants with absence of MRI lesions (Gd+ T1 lesions, new or enlarging T2 lesions) were reported. Core baseline for efficacy is defined as the last non-missing value recorded before or on randomization in the core study for each outcome measure and each participant individually. In this outcome measure, results were presented for extension end of treatment visit.

Percentage of Gd+ Lesions at Baseline Evolving to Persistent Black Holes (PBHs)
From baseline in the core study up to the end of treatment (EOT) in the extension study. The actual time varied for each participant and could be up to 94.8 months

Percentage of Gd+ lesions at baseline evolving to PBHs were reported. Core baseline for efficacy is defined as the last non-missing value recorded before or on randomization in the core study for each outcome measure and each participant individually. In this outcome measure, results were presented for extension end of treatment visit.

Number of Participants With Treatment-emergent Adverse Events (TEAEs)
From the start of study treatment in the extension study up to the end of study treatment + 15 days in the extension study. The actual time varied for each participant and could be up to 71.8 months + 15 days

Number of participants with TEAEs were reported. An AE is any untoward medical event that occurs in a participants being administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs are defined as AEs occurring from start of treatment up to treatment end date + 15 days.

Number of Participants With Treatment-emergent New Morphological Electrocardiogram (ECG) Abnormalities
From the start of study treatment in the extension study up to the end of study treatment + 15 days in the extension study. The actual time varied for each participant and could be up to 71.8 months + 15 days

Number of participants with treatment-emergent new morphological ECG abnormalities were reported. Treatment-emergent new morphological ECG abnormalities are defined as those ECG abnormalities occurring from start of treatment up to treatment end date + 15 days.

Actual Values of 12-lead ECG Measurements up to End of Study Treatment: Heart Rate
From the start of study treatment in the extension study up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months

Actual values of 12-lead ECG measurements up to end of study treatment: heart rate were reported. In this outcome measure, results were presented for extension end of treatment visit.

Actual Values of 12-lead ECG Measurements up to End of Study Treatment: PR, QRS, QT, QTcB, QTcF
From the start of study treatment in the extension study up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months

Actual values of 12-lead ECG measurements up to end of study treatment: PR, QRS, QT, QTcB, QTcF were reported. In this outcome measure, results were presented for extension end of treatment visit.

Change in Heart Rate (HR) From Baseline up to End of Study Treatment
From the start of study treatment in the extension study up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months

Change in heart rate (HR) from baseline up to end of study treatment were reported.

Change in PR, QRS, QT, QTcB, QTcF From Baseline up to End of Study Treatment
From the start of study treatment in the extension study up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months

Change in PR, QRS, QT, QTcB, QTcF from baseline up to end of study treatment were reported.

Absolute Values in Forced Expiratory Volume in 1 Second (FEV1) and Forced Vital Capacity (FVC) Values
From extension study baseline up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months

Absolute values in FEV1 and FVC values were reported. FEV1: the maximal volume of air exhaled from the lungs in 1 second of a forced expiration from a position of full inspiration as measured by spirometer. FVC: the volume of air (in liters) that can be forcibly blown out after full inspiration in the upright position. Extension baseline for safety is the last valid non-missing assessment that is taken on or after EOT visit in the core study, and prior to first study drug intake in the extension study. Results are presented for extension end of treatment visit.

Percent Change in (FEV1) and Forced Vital Capacity (FVC) From Baseline (%)
From extension study baseline up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months

Percent change in FEV1 and FVC from baseline (%) were reported. FEV1: the maximal volume of air exhaled from the lungs in 1 second of a forced expiration from a position of full inspiration as measured by spirometer. FVC: the volume of air (in liters) that can be forcibly blown out after full inspiration in the upright position. Extension baseline for safety is the last valid non-missing assessment that is taken on or after EOT visit in the core study, and prior to first study drug intake in the extension study. In this outcome measure, results were presented for extension end of treatment visit.

Number of Participants With Treatment-emergent Serious Adverse Events (SAEs)
From the start of study treatment in the extension study up to the end of study treatment + 15 days in the extension study. The actual time varied for each participant and could be up to 71.8 months + 15 days

Number of participants with treatment-emergent SAEs were reported. A SAE was defined as any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, leads to a congenital anomaly/birth defect in the offspring of a participant, or was an important medical event. Treatment-emergent SAEs are defined as SAEs occurring from start of treatment up to treatment end date + 15 days.

Number of Participants With Treatment-emergent Adverse Events of Special Interest (AESIs)
From the start of study treatment in the extension study up to the end of study treatment + 15 days in the extension study. The actual time varied for each participant and could be up to 71.8 months + 15 days

Number of participants with treatment-emergent AESIs were reported. AESIs included bradyarrhythmia occurred post-first dose, macular edema, bronchoconstriction, severe liver injury, serious opportunistic infections including progressive multifocal leukoencephalopathy (PML), skin cancer, non-skin malignancy, convulsions, unexpected neurological or psychiatric symptoms/signs (posterior reversible encephalopathy syndrome \[PRES\], acute disseminated encephalomyelitis \[ADEM\], and atypical MS relapses). Treatment-emergent AESIs are defined as AESIs occurring from start of treatment up to treatment end date + 15 days.

Number of Participants With AE Leading to Premature Discontinuation of Study Treatment
From the start of study treatment in the extension study up to the end of study treatment + 15 days in the extension study. The actual time varied for each participant and could be up to 71.8 months + 15 days

Number of participants with AE leading to premature discontinuation of study treatment were reported. An AE is any untoward medical event that occurs in a participant being administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product. TEAEs are defined as AEs occurring from start of treatment up to treatment end date + 15 days.

Number of Participants With Treatment-emergent Decrease From Baseline >20% and >30% in FEV1 or FVC
From the start of study treatment in the extension study up to the end of study treatment + 15 days in the extension study. The actual time varied for each participant and could be up to 71.8 months + 15 days

Number of participants with treatment-emergent decrease from baseline \>20% and \>30% in FEV1 or FVC were reported. Treatment-emergent is defined as events occurring from start of treatment up to treatment end date + 15 days (that is, findings not present at any assessment prior to first treatment in the extension study).

Number of Participants With Treatment-emergent Decrease of >20% Points in Percent Predicted FEV1 and FVC From Baseline
From the start of study treatment in the extension study up to the end of study treatment + 15 days in the extension study. The actual time varied for each participant and could be up to 71.8 months + 15 days

Number of participants with treatment-emergent decrease of \>20% points in percent predicted FEV1 and FVC from baseline were reported. Treatment-emergent is defined as events occurring from start of treatment up to treatment end date + 15 days (that is, findings not present at any assessment prior to first treatment in the extension study).

Number of Participants With a Decrease of >=200 mL or >=12% in FEV1 or FVC From Baseline to EOT
From extension study baseline up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months

Number of participants with a decrease of \>=200 mL or \>=12% in FEV1 or FVC from baseline to EOT were planned to be reported. Extension baseline for safety is the last valid non-missing assessment that is taken on or after EOT visit in the core study, and prior to first study drug intake in the extension study. This endpoint is not relevant as a substantial proportion of patients continued onto post-treatment disease-modifying therapy (DMT), hence it cannot provide an assessment of reversibility.

Change in FEV1 and FVC (% Predicted) From Baseline to End of Treatment (EOT)
From extension study baseline up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months

Change in FEV1 and FVC (% predicted) from baseline to EOT were predicted. Extension baseline for safety is the last valid non-missing assessment that is taken on or after EOT visit in the core study, and prior to first study drug intake in the extension study.

Change in FEV1 and FVC (% Predicted) From Baseline to End of Study (EOS)
From extension study baseline up to the end of study in the extension study. The actual time varied for each participant and could be up to 73.2 months

Change in FEV1 and FVC (% predicted) from baseline to EOS were predicted. Extension baseline for safety is the last valid non-missing assessment that is taken on or after EOT visit in the core study, and prior to first study drug intake in the extension study.

Absolute Change in Lung Diffusion Capacity as Assessed by Diffusing Capacity for the Lungs Measured Using Carbon Monoxide (DL[CO]) From Baseline
From extension study baseline up to the end of study in the extension study. The actual time varied for each participant and could be up to 73.2 months

Absolute change in lung diffusion capacity as assessed by DL\[CO\] from baseline were reported. Extension baseline for safety is the last valid non-missing assessment that is taken on or after EOT visit in the core study, and prior to first study drug intake in the extension study.

Change in DL[CO] (% Predicted) From Baseline to EOT
From extension study baseline up to the end of study treatment in the extension study. The actual time varied for each participant and could be up to 71.8 months

Change in DL\[CO\] (% predicted) from baseline to EOT were predicted. Extension baseline for safety is the last valid non-missing assessment that is taken on or after EOT visit in the core study, and prior to first study drug intake in the extension study.

Change in DL[CO] (% Predicted) From Baseline to EOS
From extension study baseline up to the end of study in the extension study. The actual time varied for each participant and could be up to 73.2 months

Change in DL\[CO\] (% predicted) from baseline to EOS were predicted. Extension baseline for safety is the last valid non-missing assessment that is taken on or after EOT visit in the core study, and prior to first study drug intake in the extension study.

Annualized Confirmed Relapse Rate
From randomization to end of study (Week 108)

Relapse: occurrence of acute episode of one or more new symptoms or worsened symptoms of Multiple sclerosis (MS), not associated with fever/infection and lasting 24 hours after stable 30 days period. Confirmed relapse: increase from baseline at least 0.5 point Expanded Disability Status Scale (EDSS) score or increase of one point in one, two or three Functional Systems (FS), excluding bowel/bladder and cerebral/mental FS. EDSS and FS scores are based on neurological examination for assessing its impairment in MS. Among eight FS, seven are ordinal clinical rating scales ranging from 0-5 or 6 with higher scale indicates overall functional impairment assessing Visual,Brain Stem,Pyramidal,Cerebellar,Sensory, Bowel/Bladder and Cerebral functions. Rating individual FS scores is used to rate EDSS in conjunction with observations and information concerning gait and use of assistance. EDSS is ordinal clinical rating scale ranging from 0 (normal neurological examination) to 10(death due to MS).

Annualized Relapse Rate (ARR) of Confirmed Relapses
From ponesimod start date up to the end of Analysis Period (AP) 3. The actual time varied for each participant and could be up to 13.3 years

ARR is defined as the number of confirmed relapses per year. A relapse is defined as the occurrence of an acute episode of one or more new symptoms, or worsening of existing symptoms of multiple sclerosis (MS), not associated with fever or infection, and lasting for at least 24 hours after a stable period of at least 30 days. A confirmed relapse is a relapse accompanied by an increase from the previous clinically stable assessment (that is, performed at least 30 days after the onset of any previous relapse) of at least 0.5 point in the Expanded Disability Status Scale (EDSS) score, or one point in the score for at least one of the Functional System (FS) scores, excluding the bowel and bladder, and mental FS. EDSS is ordinal clinical scale ranges 0 (normal neurological examination) to 10 (death due to MS).

Time to First Confirmed Relapse
From ponesimod start date up to the end of Analysis Period (AP) 3. The actual time varied for each participant and could be up to 13.3 years

Time to first confirmed relapse was reported. A relapse is defined as the occurrence of an acute episode of one or more new symptoms, or worsening of existing symptoms of multiple sclerosis (MS), not associated with fever or infection, and lasting for at least 24 hours after a stable period of at least 30 days. A confirmed relapse is a relapse accompanied by an increase from the previous clinically stable assessment (that is, performed at least 30 days after the onset of any previous relapse) of at least 0.5 point in the Expanded Disability Status Scale (EDSS) score, or one point in the score for at least one of the Functional System (FS) scores, excluding the bowel and bladder, and mental FS. EDSS is ordinal clinical scale ranges from 0 (normal neurological examination) to 10 (death due to MS).

Time to 24 Weeks Confirmed Disability Progression
From ponesimod baseline up to the end of Analysis Period (AP) 3. The actual time varied for each participant and could be up to 13.3 years

Time to 24 weeks confirmed disability progression (accumulation) was reported. Disability progression is defined as an increase of at least 1 point in the EDSS score if baseline EDSS was between 1 and 5.0, an increase of at least 1.5 points if baseline EDSS was 0, or an increase of at least 0.5 points if the baseline EDSS was equal or greater than 5.5. A 24-week confirmed disability progression is defined as a 24-week sustained increase from baseline in the EDSS scores, that is, every EDSS score (scheduled or unscheduled, with or without relapse) within a 24-week duration after the first progression should meet the progression criteria as specified above. EDSS is ordinal clinical scale ranges from 0 (normal neurological examination) to 10 (death due to MS).

Secondary Endpoints
Change From Baseline in Fatigue-related Symptoms as Measured by the Symptoms Domain of the Fatigue Symptom and Impact Questionnaire-Relapsing Multiple Sclerosis (FSIQ-RMS) Score to Week 108
Baseline to Week 108
Cumulative Number of Combined Unique Active Lesions (CUAL) Per Year From Baseline to Week 108
Baseline to Week 108
12-Week Confirmed Disability Accumulation (CDA) Assessed From Baseline to EOS
Baseline to Week 60 and 108 Weeks
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Study Design & Arms
AllocationNA
MaskingNONE
ModelSINGLE_GROUP
PurposeTREATMENT
Treatment Arms
ArmTypeDescription
PonesimodEXPERIMENTAL20 mg administered orally once daily
TeriflunomideACTIVE_COMPARATORSubjects to receive 14 mg teriflunomide
Ponesimod 10 mgEXPERIMENTALPonesimod 10 mg oral use
Ponesimod 20 mgEXPERIMENTALPonesimod 20 mg oral use
Ponesimod 40 mgEXPERIMENTALPonesimod 40 mg oral use
Interventions
NameTypeDescription
PonesimodDRUGPonesimod; Film-coated tablet; Oral use. From Day 1 to Day 14, ponesimod is gradually up-titrated until a maintenance dose of 20 mg is reached from Day 15
teriflunomideDRUGfilm-coated tablet with 14 mg teriflunomide, administered orally once daily in the morning
Ponesimod 10 mgDRUGPonesimod 10 mg oral use
Ponesimod 20 mgDRUGPonesimod 20 mg oral use
Ponesimod 40 mgDRUGPonesimod 40 mg oral use
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Eligibility Criteria
Age Range18 Years — 65 Years
SexALL
Healthy VolunteersNo
Study Sites148

Inclusion Criteria: 1. Signed informed consent 2. Subjects with MS having completed the double-blind treatment in the core study as scheduled 3. Compliance with teriflunomide elimination procedure 4. Women of childbearing potential (WOCBP) must have a negative pre-treatment urine pregnancy test, mu...

Countries:United StatesBelarusBosnia and HerzegovinaBulgariaCanadaCroatiaCzechiaFinlandFranceGeorgiaGermanyGreeceHungaryIsraelItalyLatviaLithuaniaMexicoPolandPortugalRomaniaRussiaSerbiaSpainSwedenTurkey (Türkiye)UkraineUnited KingdomAustriaNetherlandsSwitzerland
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