DEMONSTRATED IN ADULT PATIENTS
Adverse reactions occurring in ≥1% of adult patients and reported for GILENYA 0.5 mg at ≥1% higher rate than for placebo in FREEDOMS and FREEDOMS II*
Primary System Organ Class Preferred Term | GILENYA 0.5 mg n=783 (%) |
Placebo n=773 (%) |
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Infections | ||||
Influenza | 11 | 8 | ||
Sinusitis | 11 | 8 | ||
Bronchitis | 8 | 5 | ||
Herpes zoster | 2 | 1 | ||
Tinea versicolor | 2 | <1 | ||
Cardiac disorders | ||||
Bradycardia | 3 | 1 | ||
Nervous system disorders | ||||
Headache | 25 | 24 | ||
Migraine | 6 | 4 | ||
Gastrointestinal disorders | ||||
Nausea | 13 | 12 | ||
Diarrhea | 13 | 10 | ||
Abdominal pain | 11 | 10 | ||
General disorders and administration site conditions | ||||
Asthenia | 2 | 1 | ||
Musculoskeletal and connective tissue disorders | ||||
Back pain | 10 | 9 | ||
Pain in extremity | 10 | 7 | ||
Skin and subcutaneous tissue disorders | ||||
Alopecia | 3 | 2 | ||
Actinic keratosis | 2 | 1 | ||
Investigations | ||||
Liver transaminase elevations (ALT/GGT/AST) | 15 | 4 | ||
Blood triglycerides increased | 3 | 1 | ||
Respiratory, thoracic, and mediastinal disorders | ||||
Cough | 12 | 11 | ||
Dyspnea | 9 | 7 | ||
Eye disorders | ||||
Vision blurred | 4 | 2 | ||
Vascular disorders | ||||
Hypertension | 8 | 4 | ||
Blood and lymphatic system disorders | ||||
Lymphopenia | 7 | <1 | ||
Leukopenia | 2 | <1 | ||
Neoplasms benign, malignant, and unspecified (including cysts and polyps) | ||||
Skin papilloma | 3 | 2 | ||
Basal cell carcinoma | 2 | 1 |
*In placebo-controlled clinical trials (FREEDOMS and FREEDOMS II), a total of 783 adult patients received GILENYA 0.5 mg during a 2-year period.
*In placebo-controlled clinical trials (FREEDOMS and FREEDOMS II), a total of 783 adult patients received GILENYA 0.5 mg during a 2-year period.
Most common adverse reactions (≥10% and > placebo): headache, liver transaminase elevation, diarrhea, nausea, cough, influenza, sinusitis, abdominal pain, back pain, and pain in extremity
AEs that led to treatment discontinuation and occurred in more than 1% of adult patients taking GILENYA 0.5 mg were serum transaminase elevations (4.7% compared with 1% on placebo) and basal cell carcinoma (1% compared with 0.5% on placebo)
See full study designs for FREEDOMS and FREEDOMS II below
SAFETY PROFILE IN PEDIATRIC PATIENTS SIMILAR TO ADULTS1
In PARADIGMS, the controlled pediatric trial, the safety profile in pediatric patients (10 to less than 18 years of age) receiving GILENYA 0.25 mg or 0.5 mg daily was similar to that seen in adult patients
In the pediatric study, cases of seizures were reported in 5.6% of patients treated with GILENYA and 0.9% of patients treated with interferon beta-1a
The safety and efficacy of GILENYA in children less than 10 years of age have not been studied
See full PARADIGMS study design below
DEMONSTRATED SAFETY AND TOLERABILITY PROFILE IN ADULT PATIENTS2-4
UP TO 4 YEARS

*Serious AEs occurring in ≥2 patients included appendicitis, basal cell carcinoma, uterine leiomyoma, and epilepsy.
*Serious AEs occurring in ≥2 patients included appendicitis, basal cell carcinoma, uterine leiomyoma, and epilepsy.
UP TO 4.5 YEARS

*Serious AEs occurring in at least 2 patients included basal cell carcinoma, MS relapse, cholelithiasis, cystitis, breast cancer, spontaneous abortion, lower limb fracture, and road traffic accident.
*Serious AEs occurring in at least 2 patients included basal cell carcinoma, MS relapse, cholelithiasis, cystitis, breast cancer, spontaneous abortion, lower limb fracture, and road traffic accident.
UP TO 7 YEARS

*Serious AEs reported in at least 0.2% of patients were cholelithiasis, pneumonia, urinary tract infection, appendicitis, herpes zoster, basal cell carcinoma, squamous cell carcinoma, MS relapses, and depression.
*Serious AEs reported in at least 0.2% of patients were cholelithiasis, pneumonia, urinary tract infection, appendicitis, herpes zoster, basal cell carcinoma, squamous cell carcinoma, MS relapses, and depression.
POSTMARKETING EXPERIENCE
Additional serious AEs, some fatal, have been reported in the real-world, postmarketing setting
Please see Important Safety Information, including postmarketing events, below
See full FREEDOMS EXTENSION, TRANSFORMS EXTENSION, and LONGTERMS study designs below

Download the GILENYA START FORM to get your patients started now.

Download the PEDIATRIC GILENYA START FORM to get your patients (10 years of age and older) started now.
STUDY DESIGNS
A 2-year, randomized, double-blind, placebo-controlled phase III study of 1,272 adults with RRMS
Patients were randomly assigned to receive GILENYA at a once-daily dose of 0.5 mg (n=425) or 1.25 mg (n=429) or matching placebo once daily (n=418) for 2 years
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Patient baseline characteristics
Between 18 and 55 years of age
A diagnosis of RRMS with at least 1 documented relapse during the previous year or at least 2 documented relapses during the previous 2 years
A score of 0.0 to 5.5 on the EDSS. Median score at baseline was 2.0
Primary end point: ARR
Key secondary end point: time to 3-month confirmed disability progression as measured by at least a 1-point increase from baseline in EDSS (0.5-point increase for patients with baseline EDSS of 5.5) sustained for 3 months*
Additional secondary end points included number of Gd+ T1 lesions and number of new or newly enlarged lesions on T2-weighted MRI scans
The FDA-approved dose of GILENYA is 0.5 mg orally once daily. Doses higher than 0.5 mg are associated with a greater incidence of adverse reactions without additional benefits
81.2% (345/425) of patients assigned to GILENYA 0.5 mg completed the study on GILENYA 0.5 mg at 2 years while 18.8% (80/425) discontinued GILENYA
*The analysis of a key secondary end point includes the same intent-to-treat population as the primary end point(s), as well as logistic regression adjusting for certain baseline characteristics of the sample.
A 2-year, randomized, double-blind, placebo-controlled phase Ill study of 1,083 adults with RRMS
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Patient baseline characteristics
Between 18 and 55 years of age
A diagnosis of RRMS with at least 1 documented relapse during the previous year or at least 2 documented relapses during the previous 2 years
A score of 0.0 to 5.5 on the EDSS. Median score at baseline was 2.0
The primary end point was ARR
A key secondary end point was time to 3-month confirmed disability progression as measured by at least a 1-point increase from baseline in EDSS (0.5-point increase for patients with baseline EDSS of >5.0) sustained for 3 months*
Additional secondary end points included proportion of relapse-free patients and effect on MRI measurements of inflammatory disease activity (including number of Gd+ T1 lesions and number of new or newly enlarged T2 lesions)
The FDA-approved dose of GILENYA is 0.5 mg orally once daily. Doses higher than 0.5 mg are associated with a greater incidence of adverse reactions without additional benefits
PARADIGMS
A double-blind, randomized, clinical trial that compared the efficacy and safety of GILENYA 0.25 mg or 0.5 mg (dose selected based on body weight) once daily to intramuscular (IM) interferon beta-1a 30 mcg in 215 pediatric patients 10 to less than 18 years of age with RRMS. One patient received no study drug and was excluded from the analysis of efficacy
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Patient baseline characteristics
RRMS diagnosis based on the revised consensus definition for pediatric MS, which includes the 2010 McDonald criteria
Expanded Disability Status Scale (EDSS) score: 0-5.5. Median score at baseline was 1.5
Previously treated or treatment-naïve patients with at least 1 relapse in the past year, or 2 relapses in the previous 2 years, or evidence of at least 1 Gd+ T1 lesion on MRI in 6 months before randomization
No evidence of progressive MS or other immune system diseases or other demyelinating disorders, acute disseminated encephalomyelitis, or neuromyelitis optica
Primary end point: the annualized relapse rate, defined as the average number of confirmed relapses per year over the period of active treatment
Key secondary end point: the annualized rate of new or newly enlarged lesions detected on T2-weighted MRI as compared with baseline
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Other secondary end points:
Effect on Gd+ T1 lesions
Safety and tolerability
Patients were required to remain at the site for at least 6 hours after receiving the first dose of study drug (ie, first-dose monitoring on Day 1). First-dose observation included monitoring of vital signs (heart rate and blood pressure), for potential signs of bradycardia, and electrocardiography
Prior therapy with interferon-beta, dimethyl fumarate, or glatiramer acetate up to the time of randomization was permitted
Baseline assessments and neurologic evaluations were performed at screening. Additional neurological evaluations were completed every 3 months and at the time of suspected relapses
MRI evaluations were performed at screening, and every 6 months throughout the study
EXTENSION
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An optional, dose-blinded, parallel-group extension study of 1,033 adults with RRMS who completed the core FREEDOMS study on either a once-daily dose of GILENYA 0.5 mg or 1.25 mg or matching placebo once daily for 2 years. Efficacy and safety were evaluated at 48 months
Of the 1,272 patients who completed the core trial, 1,033 (81.2%) opted to continue on the extension study
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All patients in the extension either continued GILENYA 0.5 mg/day or 1.25 mg/day, or switched from placebo to either dose, randomized 1:1
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Patient baseline characteristics
Eligible for inclusion in the core study with a diagnosis of RRMS and 1 or more documented relapses in the year before randomization, or 2 or more documented relapses in the 2 years prior to randomization
A score of 0 to 5.5 on the EDSS. Median score at baseline was 2.0
Aged 18 to 55 years
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Primary end point: ARR
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Between-group analyses were conducted in the intent-to-treat (ITT) population from FREEDOMS baseline to end of study
Within-group analyses compared years 0 to 2 (FREEDOMS) and years 2 to 4 (extension) in the extension ITT population
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The FDA-approved dose of GILENYA is 0.5 mg orally once daily. Doses higher than 0.5 mg are associated with a greater incidence of adverse reactions without additional benefits
EXTENSION
An optional, 12-month, randomized phase III extension study of 1,027 adults with RRMS who completed the core TRANSFORMS study on either IFNβ-1a IM 30 mcg, GILENYA 0.5 mg, or GILENYA 1.25 mg. Efficacy and safety were followed up to 4.5 years
Of the 1,123 patients who completed the core trial, 1,027 (92%) opted to continue on the extension study
All patients in the extension received a once-daily dose of either GILENYA 0.5 mg or GILENYA 1.25 mg
Patients who received GILENYA during the TRANSFORMS core trial continued at their prior dosage of either 0.5 mg (n=356) or 1.25 mg (n=330)
Patients who received IFNβ-1a IM 30 mcg during the TRANSFORMS core trial were randomly assigned to receive GILENYA at a once-daily dose of 0.5 mg (n=167) or 1.25 mg (n=174)
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Patient baseline characteristics
Eligible for inclusion in the core study with a diagnosis of RRMS and 1 or more documented relapses in the year before randomization, or 2 or more documented relapses in the 2 years prior to randomization
A score of 0 to 5.5 on the EDSS. Median score at baseline was 2.0
Aged 18 to 55 years
Neurologically stable, with no evidence of relapse or corticosteroid treatment within 30 days before randomization
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Efficacy end points were ARR, disability progression, and MRI outcomes
No variable was specifically designated as the "primary variable" in the extension phase
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Core phase
Primary efficacy variable was the aggregate ARR
Key secondary variables were the number of new or newly enlarged T2 lesions and the time to first 3-month confirmed disability progression as measured by EDSS*
For patients who transitioned to GILENYA, leading causes of discontinuation were withdrawal of consent, unsatisfactory therapeutic effect, and adverse events
For patients who continued on GILENYA, leading causes of discontinuation were withdrawal of consent, abnormal laboratory values, and adverse events
The FDA-approved dose of GILENYA is 0.5 mg orally once daily. Doses higher than 0.5 mg are associated with a greater incidence of adverse reactions without additional benefits
LONGTERMS
An open-label, single-arm, long-term follow-up extension study of phase II, phase Ill, and phase lllb trials, monitoring the long-term safety, tolerability, and effectiveness of GILENYA 0.5 mg in adults with RRMS
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Safety analysis
This analysis included the core plus extension periods of the phase Ill trials (FREEDOMS, TRANSFORMS, FREEDOMS II)
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Two patient cohorts treated with fingolimod 0.5 mg were evaluated:
A long-term cohort (LC; n=1,655) previously enrolled in the 3 core phase Ill trials plus their extensions (including nonparticipants of LONGTERMS)
A core cohort (CC; n=1,212) pooled from core phase Ill trials
AE=adverse event; ALT=alanine aminotransferase; ARR=annualized relapse rate; AST=aspartate aminotransferase; EDSS=Expanded Disability Status Scale; Gd+=gadolinium-enhancing; GGT=gamma-glutamyl transpeptidase; IFN=interferon; IM=intramuscular; MRI=magnetic resonance imaging; MS=multiple sclerosis; RRMS=relapsing-remitting multiple sclerosis.
References: 1. Gilenya [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; December 2019. 2. Kappos L, O'Connor P, Radue E-W, et al. Long-term effects of fingolimod in multiple sclerosis: the randomized FREEDOMS extension trial. Neurology. 2015;84(15):1582-1591. 3. Cohen JA, Khatri B, Barkhof F, et al; TRANSFORMS (TRial Assessing injectable interferoN vS. FTY720 Oral in RRMS) Study Group. Long-term (up to 4.5 years) treatment with fingolimod in multiple sclerosis: results from the extension of the randomised TRANSFORMS study. J Neurol Neurosurg Psychiatry. 2016;87(5):468-475. 4. Data on file. LONGTERMS Full Clinical Study Report (CFTY720D2399). Novartis Pharmaceuticals Corp; November 2017.
References: 1. Gilenya [prescribing information]. East Hanover, NJ: Novartis Pharmaceuticals Corp; December 2019. 2. Kappos L, O'Connor P, Radue E-W, et al. Long-term effects of fingolimod in multiple sclerosis: the randomized FREEDOMS extension trial. Neurology. 2015;84(15):1582-1591. 3. Cohen JA, Khatri B, Barkhof F, et al; TRANSFORMS (TRial Assessing injectable interferoN vS. FTY720 Oral in RRMS) Study Group. Long-term (up to 4.5 years) treatment with fingolimod in multiple sclerosis: results from the extension of the randomised TRANSFORMS study. J Neurol Neurosurg Psychiatry. 2016;87(5):468-475. 4. Data on file. LONGTERMS Full Clinical Study Report (CFTY720D2399). Novartis Pharmaceuticals Corp; November 2017.