This Was an Open-label, Single-arm Extension Study (CFTY720D2306E1) to a Double-blind, Randomized Multicenter, Placebo-controlled, Parallel-group Core Study (CFTY720D2306) in PPMS.

3-month sustained increase from Baseline in EDSS (at least 1 point increase from Baseline for patients with a Baseline value of 5 or less or at least 0.5 point increase from Baseline for patients with a Baseline value of 5.5 or more) or 3-month sustained increase of at least 20% from BL in the time taken to complete the timed 25-foot walk test (25' TWT); or 3-month sustained increase of at least 20% from BL in the time taken to complete the 9-HPT. The 25' TWT is a quantitative measure of lower extremity function. The EDSS is a scale assessing neurologic impairment, including a series of scores in each of 8 functional systems: Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, Cerebral and Other functions. The score ranges from 0 (normal) to 10 (death due to MS)). The 9-hole peg test (9-HPT) is a quantitative measure of upper extremity (arm and hand) function.

Time frame: up to 36 months after the last patient was randomized

Population: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo.

Concentrations of fingolimod and fingolimod-phosphate in whole blood were determined by validated liquid chromatography methods with tandem mass spectrometry. The lower limits of quantification were 0.08 ng/ml for fingolimod and 0.1 ng/ml for fingolimod-phosphate. Venous blood samples were collected for the analysis.

Time frame: Month 3 up to 36 months

Population: Full analysis set (FAS) -The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo. (N). Only participants (n) who provided one or more evaluable blood concentration were included in the pharmacokinetic analysis population. Analysis include 147 patients (cohort 1)

EQ-5D: participant rated questionnaire to assess health-related quality of life in terms of a single utility score. Health State Profile component assesses level of current health for 5 domains: mobility, self care, usual activities, pain and discomfort, and anxiety and depression; 1 indicates better health state (no problems); 3 indicates worst health state (confined to bed). Scoring formula developed by EuroQoL Group assigns a utility value for each domain in the profile. Score is transformed and results in a total score range -0.594 to 1.000; higher score indicates a better health state.

Time frame: Baseline, 36 months

Population: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo. Only subjects with a value at both baseline and at month 36 are included.

The Multiple Sclerosis Walking Scaleis a patient reported measure of walking quality (Hobart et al 2003), consisting of 12 items asking patients to rate the impact of MS upon their walking ability. Responses were captured on a 3-point scale ranging from 1 (Not at all) to 3 (A lot) for items 1 to 3 and on a 5-point scale ranging from 1 (not limited) to 5 (extremely) for items 4 to 12. All 12 item scores were summed to obtain a total score ranging from 12 (good) to 54 (poor) which is the MSWS-12 scale score. The total score was transformed to a 0 to 100 scale score. The MSWS-12 scale score will be transformed to a 0-100 scale score before any summaries or statistical analyses are performed. The transformed score is obtained by subtracting 12 and divided by 42 and multiplying by 100 (i.e., transformed scale score = (raw scale score- 12)/42\*100).

Time frame: Baseline, 36 months

Population: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo. Only subjects with a value at both baseline and at month 36 are included.

The activities subscale of PRIMUS contains 15 items and each item is given a score of 0 (able to do on own without difficulties), 1 (able to do on own with difficulties), or 2 (unable to do on own). All 15 items were summed to obtain a total score ranging from 0 (good) to 30 (poor).

Time frame: Baseline, 36 months

Population: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo. Only subjects with a value at both baseline and at month 36 are included.

The quality of life scale contains 22 items. Each item will be given a score of 1 or 0. A score of 1 (or 0) indicates the presence (or absence) of the symptom or adverse quality of life. All 22 item scores will be summed to obtain a total score ranging from 0 (good) to 22 (poor), which is the PRIMUS QoL scale score

Time frame: Baseline, 36 months

Population: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo. Only subjects with a value at both baseline and at month 36 are included.

Unidimensional Fatigue Impact Scale (U-FIS), contains 22 patient-reported items that assess the impact of fatigue on cognitive, physical, and psychosocial functioning. Responses formed a single unidimensional scale measuring fatigue impact. The U-FIS was calculated and analyzed according to the U-FIS scoring manual. The U-FIS scale contains 22 items with 5 possible outcomes for each item. Two response categories (about half the time and a lot of the time) were combined into 1 category to obtain 4 possible outcomes: 0 (never), 1 (a little of the time), 2 (about half the time/a lot of the time), and 3 (all the time). The 22 condensed item scores were summed to obtain a total score ranging from 0 (no fatigue) to 66 (severe fatigue impact).

Time frame: Baseline, 36 months

Population: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo. Only subjects with a value at both baseline and at month 36 are included.

The Multiple Sclerosis Functional Composite (MSFC) is a multidimensional clinical outcome measure that includes quantitative tests of leg function/ambulation (Timed 25-Foot Walk), arm function (9-Hole Peg Test), and cognitive function (Paced Auditory Serial Addition Test). The overall MSFC z-score as an average of the three standardized scores derived using baseline data pooled over each treatment arm as reference population. Higher scores reflect better neurological function and a positive change from Baseline indicates improvement.

Time frame: Baseline to Month 36

Population: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS

The Expanded Disability Status Scale (EDSS) is a scale for assessing neurologic impairment in MS (Kurtzke 1983) and includes a series of scores in each of 8 functional systems and the EDSS steps (ranging from 0 (normal) to 10 (death due to MS)). The functional systems are Visual, Brain Stem, Pyramidal, Cerebellar, Sensory, Bowel and Bladder, Cerebral and Other functions. Fatigue is not included in the Cerebral score of the EDSS. The score ranges from 0 (normal) to 10 (death due to MS)

Time frame: up to 36 months after the last patient was randomized

Population: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo.

The 25' TWT is a quantitative measure of lower extremity function designed and validated for evaluation of MS patients. N= Total number of patients included in the analysis

Time frame: up to 36 months after the last patient was randomized

Population: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo.

The 9-HPT is a quantitative measure of upper extremity (arm and hand) function designed and validated for evaluation of MS patients. N= Total number of patients included in the analysis

Time frame: up to 36 months after the last patient was randomized

Population: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo.

Inflammatory disease, as measured by number of T1 Gd-enhancing lesions, was assessed by MRI scanning of the brain and full spinal cord. N= Total number of patients included in the analysis

Time frame: Baseline to 36 months

Population: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo.

Inflammatory disease, as measured by number of new or newly-enlarging T2 lesions, was assessed by Magnetic resonance Imaging (MRI) scanning of the brain and full spinal cord. N= Total number of patients included in the analysis

Time frame: Baseline to 36 months

Population: Full analysis set (FAS) -The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo.

The percent change from Baseline in brain volume was analyzed using a random coefficients model. The model included: 1) fixed effects: treatment and region and 2) continuous covariates: time, number of Gd enhancing lesions at Baseline, Baseline T2 volume, and normalized brain volume at Baseline. Time as a continuous covariate allowed for the estimation of different slopes and intercepts among treatment groups.

Time frame: Baseline to month 36

Population: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo. N= Total number of patients included in the analysis.

Inflammatory disease as measured by percent change in total T2 lesion volume (mm3) was assessed by MRI. N= Total number of patients included in the analysis

Time frame: Baseline to month 36

Population: Full analysis set (FAS) - The main efficacy analyses were performed using the FAS, in patients who were initially randomized to either FTY 0.5mg or to Placebo.