Sanofi Genzyme Global

AUBAGIO® (teriflunomide) is indicated for the treatment of patients with relapsing
forms of multiple sclerosis.

WARNING: HEPATOTOXICITY AND RISK OF TERATOGENICITY
Severe liver injury including fatal liver failure has been reported in patients treated
with leflunomide, which is indicated for rheumatoid arthritis.
Please see Important Safety Information and Full Prescribing Information,
including boxed WARNING.
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The proven efficacy of AUBAGIO in quieting* RMS1

*AUBAGIO is effective across key measures of disease activity: sustained disability progression (14 mg only), annualized relapse rate, and MRI activity. Overall discontinuation rates due to adverse events were 12.5% with AUBAGIO 14 mg, 11.2% with AUBAGIO 7 mg, and 7.5% with placebo, and treatment discontinuation rates due to common adverse events were ≤3.3% in the pooled clinical trials.1,2

The efficacy of AUBAGIO® (teriflunomide) 14 mg was established and confirmed in 4 clinical trials1


The majority of patients remained free from disability progression with AUBAGIO 14 mg1

An estimated 80%
in TEMSO over 108 weeks (P=0.03)1‡
TEMSO: AUBAGIO 14 mg significantly
reduced the risk of sustained disability progression versus placebo1
AUBAGIO® (teriflunomide) clinical trial 1: TESMO –30% relative risk reduction of sustained disability progression with AUBAGIO 14 mg
  • The estimated proportion of patients with sustained disability progression at week 108 was 20.2%, 21.7%, and 27.3% with AUBAGIO 14 mg, AUBAGIO 7 mg, and placebo, respectively1
  • AUBAGIO 7 mg did not achieve a statistically significant reduction in risk of sustained disability progression versus placebo1
An estimated 84%
in TOWER over 108 weeks (P<0.05)1‡
tower: AUBAGIO 14 mg significantly
reduced the risk of sustained disability progression versus placebo1
AUBAGIO® (teriflunomide) clinical trial 2: TOWER –31% relative risk reduction of sustained disability progression with AUBAGIO 14 mg
  • The estimated proportion of patients with sustained disability progression at week 108 was 15.8%, 21.1%, and 19.7% with AUBAGIO 14 mg, AUBAGIO 7 mg, and placebo, respectively1
  • AUBAGIO 7 mg did not achieve a statistically significant reduction in risk of sustained disability progression versus placebo1

Sustained disability progression was defined as at least a 1-point increase from baseline Expanded Disability Status Scale (EDSS) score ≤5.5 (or at least a 0.5-point increase for those with a baseline EDSS score >5.5) sustained for at least 12 weeks.1


TEMSO: A double-blind, placebo-controlled trial in patients with relapsing forms of MS (N=1088). Patients were randomized to receive AUBAGIO 14 mg (n=359), AUBAGIO 7 mg (n=366), or placebo (n=363) once daily for 108 weeks.3

TOWER: A double-blind, placebo-controlled trial in patients with relapsing forms of MS (N=1169). Patients were randomized to receive AUBAGIO 14 mg (n=372), AUBAGIO 7 mg (n=408), or placebo (n=389) once daily with results for up to 40 months of treatment.4

Disability progression was a secondary endpoint in TEMSO and TOWER.3,4

Based on Kaplan-Meier estimates.1

Phase III

TEMSO1,3

TOWER1,4

(N=1088)

RMS PATIENTS§

  • Mean time from first symptom: 9 years
  • The mean baseline EDSS was 2.7
  • The average age was 38
  • 73% were untreated within 2 years of
    starting the trial
Phase III

TOWER1,4

(N=1169)

RMS PATIENTSII

  • Mean time from first symptom: 8 years
  • The mean baseline EDSS was 2.7
  • The average age was 38
  • 67% were untreated within 2 years of
    starting the trial

§ In the TEMSO trial, 91% of patients had RMS, and 9% had a progressive form of MS with relapses.1

II In the TOWER trial, 98% of patients had RMS, and 2% had a progressive form of MS with relapses.1

Also proven in Trial 3: TOPIC1
Back to TEMSO and TOWER

In patients who had a first clinical event characteristic
of RMS, AUBAGIO 14 mg provided freedom from relapses1

72% IN TOPIC
remained
relapse
free
VS 62% WITH PLACEBO (P<0.05)1
  • TOPIC studied patients who had a first clinical event consistent with acute demyelination occurring within 90 days of randomization1
  • Patients had a mean EDSS of 1.7 at baseline1
  • The average age was 32 years1
  • Patients had a first clinical event characteristic of RMS 2 months before the start of the trial6

Phase III

TOPIC1,6
(N=618)
NEWLY DIAGNOSED
RMS PATIENTS
  • Mean time from first symptom:
    2 months
  • The mean baseline EDSS was 1.7
  • The average age was 32
  • 100% of patients were
    previously untreated

TOPIC: A double-blind, placebo-controlled trial in patients with relapsing forms of MS (N=618). Patients were randomized to receive AUBAGIO 14 mg (n=216), AUBAGIO 7 mg (n=205), or placebo (n=197) once daily for 108 weeks. Patients had a first clinical event consistent with acute demyelination occurring within 90 days of randomization with 2 or more T2 lesions at least 3 mm in diameter characteristic of RMS.6

The majority of patients taking AUBAGIO 14 mg remained free from relapse over 108 weeks1

An estimated 57% IN TEMSO
remained
relapse
free
over 108 weeks (HR=0.72)1,3
  • Versus 46% with placebo1
  • 54% of patients remained relapse free with AUBAGIO 7 mg in the TEMSO trial1
TEMSO: AUBAGIO 14 mg SIGNIFICANTLY REDUCED ARR VERSUS PLACEBO1 AUBAGIO® (teriflunomide) clinical trial 1: TESMO – 31% relative risk reduction in relapse rate
  • AUBAGIO 14 mg and 7 mg achieved a significant relative reduction in risk of relapse in TEMSO (31% for both doses; P<0.05)1
An estimated 57% IN TOWER
remained relapse
free
over 108 weeks (HR=0.63)1,5
  • Versus 47% with placebo1
  • 58% of patients remained relapse free with AUBAGIO 7 mg in the TOWER trial1
TOWER: AUBAGIO 14 mg SIGNIFICANTLY REDUCED ARR VERSUS PLACEBO1 AUBAGIO® (teriflunomide) clinical trial 2: TOWER – 36% relative risk reduction in relapse rate
  • AUBAGIO 14 mg and 7 mg achieved a significant relative reduction in risk of relapse in TOWER (36% and 22%, respectively; P<0.05)1

TEMSO: A double-blind, placebo-controlled trial in patients with relapsing forms of MS (N=1088). Patients were randomized to receive AUBAGIO 14 mg (n=359), AUBAGIO 7 mg (n=366), or placebo (n=363) once daily for 108 weeks.3

TOWER: A double-blind, placebo-controlled trial in patients with relapsing forms of MS (N=1169). Patients were randomized to receive AUBAGIO 14 mg (n=372), AUBAGIO 7 mg (n=408), or placebo (n=389) once daily with results for up to 40 months of treatment.4

Phase III

TEMSO1,3

TOWER1,4

(N=1088)

RMS PATIENTS§

  • Mean time from first symptom: 9 years
  • The mean baseline EDSS was 2.7
  • The average age was 38
  • 73% were untreated within 2 years of
    starting the trial
Phase III

TOWER1,4

(N=1169)

RMS PATIENTSII

  • Mean time from first symptom: 8 years
  • The mean baseline EDSS was 2.7
  • The average age was 38
  • 67% were untreated within 2 years of
    starting the trial

§ In the TEMSO trial, 91% of patients had RMS, and 9% had a progressive form of MS with relapses.1

II In the TOWER trial, 98% of patients had RMS, and 2% had a progressive form of MS with relapses.1

TEMSO: Significant effect on MRI activity over 108 weeks with AUBAGIO 14 mg1,3
80%
FEWER Gd-ENHANCING
T1 LESIONS1,3
  • Mean of 0.261 lesions with AUBAGIO 14 mg versus 1.331 for placebo (P<0.0001)1
  • Mean of 0.570 lesions with AUBAGIO 7 mg (P<0.0001)1
  • 56% fewer lesions with AUBAGIO 7 mg (P<0.001)7
69%
REDUCTION IN
CHANGE IN TOTAL
LESION VOLUME1
  • Median change of 0.345 mL for AUBAGIO 14 mg versus 1.127 mL for placebo (P=0.0003)1
  • Median change of 0.755 mL for AUBAGIO 7 mg (P=0.0317)1
  • 33% reduction with AUBAGIO 7 mg (P=0.0317)1
64%
OF PATIENTS WERE FREE
FROM Gd-ENHANCING
T1 LESIONS3
  • 64% were free with AUBAGIO 14 mg versus 39% with placebo (P<0.001)3
  • 51% were free with AUBAGIO 7 mg (P<0.001)3
Study 4: Significant effect on new MRI
activity demonstrated over 36 weeks
with AUBAGIO 14 mg1
64%
FEWER UNIQUE
ACTIVE LESIONS1
  • Mean of 0.98 lesions with AUBAGIO 14 mg versus 2.69 with placebo (P=0.0052)1
  • Mean of 1.06 lesions with AUBAGIO 7 mg (P=0.0234)1
  • 61% fewer lesions with AUBAGIO 7 mg (P=0.0234)1

Gd=gadolinium.

TEMSO: A double-blind, placebo-controlled trial in patients with relapsing forms of MS (N=1088). Patients were randomized to receive AUBAGIO 14 mg (n=359), AUBAGIO 7 mg (n=366), or placebo (n=363) once daily for 108 weeks.3

STUDY 4: A double-blind, placebo-controlled trial in patients with relapsing forms of MS (N=179). Patients were randomized to receive AUBAGIO 14 mg (n=57), AUBAGIO 7 mg (n=61), or placebo (n=61) once daily for 36 weeks.8

Phase III

TEMSO1,3

Phase II

STUDY 41,8

(N=1088)

RMS PATIENTS

  • Mean time from first symptom: 8 years
  • The mean baseline EDSS was 2.7
  • The average age was 38
  • 67% were untreated within 2 years of
    starting the trial
Phase II

STUDY 41,8

(N=179)

RMS PATIENTS

  • Mean time from first symptom: 9 years
  • The median baseline EDSS was 2.3
  • The average age was 40
  •  
  •  

In the TEMSO trial, 91% of patients had RMS, and 9% had a progressive form of MS with relapses.1

In the Phase II trial, 88% of patients had RMS, and 12% had secondary progressive MS.8

ARR=annualized relapse rate; HR=hazard ratio.

INDICATION

AUBAGIO® (teriflunomide) is indicated for the treatment of patients with relapsing forms of multiple sclerosis.


IMPORTANT SAFETY INFORMATION WARNING: HEPATOTOXICITY AND RISK OF TERATOGENICITY
  • Severe liver injury including fatal liver failure has been reported in patients treated with leflunomide, which is indicated for rheumatoid arthritis. A similar risk would be expected for teriflunomide because recommended doses of teriflunomide and leflunomide result in a similar range of plasma concentrations of teriflunomide. Concomitant use of AUBAGIO with other potentially hepatotoxic drugs may increase the risk of severe liver injury.
  • Obtain transaminase and bilirubin levels within 6 months before initiation of AUBAGIO therapy. Monitor ALT levels at least monthly for 6 months after starting AUBAGIO. If drug-induced liver injury is suspected, discontinue AUBAGIO and start an accelerated elimination procedure with cholestyramine or activated charcoal. AUBAGIO is contraindicated in patients with severe hepatic impairment. Patients with pre-existing liver disease may be at increased risk of developing elevated serum transaminases when taking AUBAGIO.
  • AUBAGIO is contraindicated for use in pregnant women and in women of reproductive potential who are not using effective contraception because of the potential for fetal harm. Teratogenicity and embryolethality occurred in animals at plasma teriflunomide exposure lower than that in humans. Exclude pregnancy before the start of treatment with AUBAGIO in females of reproductive potential. Advise females of reproductive potential to use effective contraception during AUBAGIO treatment and during an accelerated drug elimination procedure after AUBAGIO treatment. Stop AUBAGIO and use an accelerated drug elimination procedure if the patient becomes pregnant.
CONTRAINDICATIONS
  • Patients with severe hepatic impairment.
  • Pregnant women and females of reproductive potential not using effective contraception.
  • Patients with a history of hypersensitivity reaction to teriflunomide, leflunomide, or to any of the inactive ingredients in AUBAGIO.
  • Co-administration with leflunomide.
WARNINGS AND PRECAUTIONS
  • Hepatotoxicity: Patients with pre-existing acute or chronic liver disease, or those with serum ALT >2 times the upper limit of normal (ULN) before initiating treatment, should not normally be treated with AUBAGIO. In clinical trials, if ALT elevation was >3 times the ULN on 2 consecutive tests, patients discontinued AUBAGIO and underwent accelerated elimination. Consider additional monitoring if co-administering AUBAGIO with other potentially hepatotoxic drugs; monitor patients who develop symptoms suggestive of hepatic dysfunction (eg, unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine).
  • Teratogenicity: AUBAGIO may cause fetal harm when administered in pregnant women. Teratogenicity and embryo-fetal lethality occurred in animal reproduction studies in multiple animal species at plasma teriflunomide exposures similar to or lower than that in humans at the maximum human recommended dose of 14 mg/day. AUBAGIO is contraindicated for use in pregnant women and females of reproductive potential not using effective contraception. Women who become pregnant while taking AUBAGIO may enroll in the AUBAGIO pregnancy registry by calling 1-800-745-4447, option 2.
  • Procedure for Accelerated Elimination of Teriflunomide: Teriflunomide is eliminated slowly from the plasma—it takes an average of 8 months, or up to 2 years, to reach plasma concentrations <0.02 mcg/mL. Elimination may be accelerated by administration of cholestyramine or activated charcoal, but this may cause disease activity to return in patients who were responding to AUBAGIO.
  • Bone Marrow Effects/Immunosuppression Potential/Infections: Decreases in white blood cell counts, mainly of neutrophils and lymphocytes, and platelets have been reported with AUBAGIO. Thrombocytopenia, including rare cases with platelet counts less than 50,000/mm3, has been reported in the postmarketing setting. Obtain a complete blood cell count within 6 months before starting treatment, with further monitoring based on signs and symptoms of bone marrow suppression. AUBAGIO is not recommended for patients with severe immunodeficiency, bone marrow disease, or severe uncontrolled infections. Tuberculosis (TB) has been observed in clinical studies of AUBAGIO. Before starting treatment, screen patients for latent TB infection with a tuberculin test. Treatment in patients with acute or chronic infections should not be started until the infection(s) is resolved. Administration of live vaccines is not recommended. The risk of malignancy, particularly lymphoproliferative disorders, or infection may be increased with the use of some medications with immunosuppressive potential, including teriflunomide.
  • Hypersensitivity and Serious Skin Reactions: AUBAGIO can cause anaphylaxis and severe allergic reactions. Signs and symptoms have included dyspnea, urticaria, and angioedema including lips, eyes, throat, and tongue. Cases of serious skin reactions, including Stevens-Johnson syndrome and a fatal case of toxic epidermal necrolysis, have been reported with AUBAGIO. Very rare cases of Drug Reaction with Eosinophilia and Systemic Symptoms have also been reported with leflunomide. If a severe skin reaction develops with AUBAGIO, stop treatment and begin accelerated elimination. In such cases, patients should not be re-exposed to teriflunomide.
  • Peripheral Neuropathy: Peripheral neuropathy, including polyneuropathy and mononeuropathy, has been reported with AUBAGIO. Age >60 years, concomitant neurotoxic medications, and diabetes may increase the risk. If peripheral neuropathy is suspected, consider discontinuing treatment and performing accelerated elimination.
  • Increased Blood Pressure: Blood pressure increases and hypertension have occurred with AUBAGIO. Measure blood pressure at treatment initiation and manage any elevations during treatment.
  • Respiratory Effects: Interstitial lung disease (ILD), including acute interstitial pneumonitis, has been reported with AUBAGIO. ILD may be fatal and may occur acutely at any time during therapy with a variable clinical presentation. If discontinuation of the drug is necessary, consider initiation of an accelerated elimination procedure.

Adverse Reactions: The most frequent adverse reactions (≥10% and ≥2% greater than placebo) with AUBAGIO 7 mg and 14 mg and placebo, respectively, were headache (18% and 16% vs 15%), ALT increased (13% and 15% vs 9%), diarrhea (13% and 14% vs 8%), alopecia (10% and 13% vs 5%), and nausea (8% and 11% vs 7%).

Drug Interactions: Monitor patients when teriflunomide is coadministered with warfarin, or with drugs metabolized by CYP1A2, CYP2C8, substrates of OAT3 transporters, substrates of BCRP, or OATP1B1/1B3 transporters.

Use in Specific Populations: Women who wish to become pregnant should discontinue AUBAGIO and undergo an accelerated elimination procedure. Use of effective contraception should be continued until plasma concentrations of teriflunomide are <0.02 mcg/mL. Nursing mothers should not use AUBAGIO. AUBAGIO is detected in human semen. To minimize any possible fetal risk, men not wishing to father a child and their female partners should use effective contraception. Men wishing to father a child should discontinue therapy and either undergo accelerated elimination or verify plasma teriflunomide concentration is <0.02 mcg/mL.

Please see Full Prescribing Information, including boxed WARNING for further information.

Important Safety Information, including boxed WARNING.
INDICATION

AUBAGIO® (teriflunomide) is indicated for the treatment of patients with relapsing forms of multiple sclerosis.

IMPORTANT SAFETY INFORMATION WARNING: HEPATOTOXICITY AND RISK OF TERATOGENICITY
  • Severe liver injury including fatal liver failure has been reported in patients treated with leflunomide, which is indicated for rheumatoid arthritis. A similar risk would be expected for teriflunomide because recommended doses of teriflunomide and leflunomide result in a similar range of plasma concentrations of teriflunomide. Concomitant use of AUBAGIO with other potentially hepatotoxic drugs may increase the risk of severe liver injury.
  • Obtain transaminase and bilirubin levels within 6 months before initiation of AUBAGIO therapy. Monitor ALT levels at least monthly for 6 months after starting AUBAGIO. If drug-induced liver injury is suspected, discontinue AUBAGIO and start an accelerated elimination procedure with cholestyramine or activated charcoal. AUBAGIO is contraindicated in patients with severe hepatic impairment. Patients with pre-existing liver disease may be at increased risk of developing elevated serum transaminases when taking AUBAGIO.
  • AUBAGIO is contraindicated for use in pregnant women and in women of reproductive potential who are not using effective contraception because of the potential for fetal harm. Teratogenicity and embryolethality occurred in animals at plasma teriflunomide exposure lower than that in humans. Exclude pregnancy before the start of treatment with AUBAGIO in females of reproductive potential. Advise females of reproductive potential to use effective contraception during AUBAGIO treatment and during an accelerated drug elimination procedure after AUBAGIO treatment. Stop AUBAGIO and use an accelerated drug elimination procedure if the patient becomes pregnant.
CONTRAINDICATIONS
  • Patients with severe hepatic impairment
  • Pregnant women and females of reproductive potential not using effective contraception
  • Patients with a history of hypersensitivity reaction to teriflunomide, leflunomide, or to any of the inactive ingredients in AUBAGIO.
  • Co-administration with leflunomide.
WARNINGS AND PRECAUTIONS
  • Hepatotoxicity: Patients with pre-existing acute or chronic liver disease, or those with serum ALT >2 times the upper limit of normal (ULN) before initiating treatment, should not normally be treated with AUBAGIO. In clinical trials, if ALT elevation was >3 times the ULN on 2 consecutive tests, patients discontinued AUBAGIO and underwent accelerated elimination. Consider additional monitoring if co-administering AUBAGIO with other potentially hepatotoxic drugs; monitor patients who develop symptoms suggestive of hepatic dysfunction (eg, unexplained nausea, vomiting, abdominal pain, fatigue, anorexia, or jaundice and/or dark urine).
  • Teratogenicity: AUBAGIO may cause fetal harm when administered in pregnant women. Teratogenicity and embryo-fetal lethality occurred in animal reproduction studies in multiple animal species at plasma teriflunomide exposures similar to or lower than that in humans at the maximum human recommended dose of 14 mg/day. AUBAGIO is contraindicated for use in pregnant women and females of reproductive potential not using effective contraception. Women who become pregnant while taking AUBAGIO may enroll in the AUBAGIO pregnancy registry by calling 1-800-745-4447, option 2.
  • Procedure for Accelerated Elimination of Teriflunomide: Teriflunomide is eliminated slowly from the plasma—it takes an average of 8 months, or up to 2 years, to reach plasma concentrations <0.02 mcg/mL. Elimination may be accelerated by administration of cholestyramine or activated charcoal, but this may cause disease activity to return in patients who were responding to AUBAGIO.
  • Bone Marrow Effects/Immunosuppression Potential/Infections: Decreases in white blood cell counts, mainly of neutrophils and lymphocytes, and platelets have been reported with AUBAGIO. Thrombocytopenia, including rare cases with platelet counts less than 50,000/mm3, has been reported in the postmarketing setting. Obtain a complete blood cell count within 6 months before starting treatment, with further monitoring based on signs and symptoms of bone marrow suppression. AUBAGIO is not recommended for patients with severe immunodeficiency, bone marrow disease, or severe uncontrolled infections. Tuberculosis (TB) has been observed in clinical studies of AUBAGIO. Before starting treatment, screen patients for latent TB infection with a tuberculin test. Treatment in patients with acute or chronic infections should not be started until the infection(s) is resolved. Administration of live vaccines is not recommended. The risk of malignancy, particularly lymphoproliferative disorders, or infection may be increased with the use of some medications with immunosuppressive potential, including teriflunomide.
  • Hypersensitivity and Serious Skin Reactions: AUBAGIO can cause anaphylaxis and severe allergic reactions. Signs and symptoms have included dyspnea, urticaria, and angioedema including lips, eyes, throat, and tongue. Cases of serious skin reactions, including Stevens-Johnson syndrome and a fatal case of toxic epidermal necrolysis, have been reported with AUBAGIO. Very rare cases of Drug Reaction with Eosinophilia and Systemic Symptoms have also been reported with leflunomide. If a severe skin reaction develops with AUBAGIO, stop treatment and begin accelerated elimination. In such cases, patients should not be re-exposed to teriflunomide.
  • Peripheral Neuropathy: Peripheral neuropathy, including polyneuropathy and mononeuropathy, has been reported with AUBAGIO. Age >60 years, concomitant neurotoxic medications, and diabetes may increase the risk. If peripheral neuropathy is suspected, consider discontinuing treatment and performing accelerated elimination.
  • Increased Blood Pressure: Blood pressure increases and hypertension have occurred with AUBAGIO. Measure blood pressure at treatment initiation and manage any elevations during treatment.
  • Respiratory Effects: Interstitial lung disease (ILD), including acute interstitial pneumonitis, has been reported with AUBAGIO. ILD may be fatal and may occur acutely at any time during therapy with a variable clinical presentation. If discontinuation of the drug is necessary, consider initiation of an accelerated elimination procedure.

Adverse Reactions: The most frequent adverse reactions (≥10% and ≥2% greater than placebo) with AUBAGIO 7 mg and 14 mg and placebo, respectively, were headache (18% and 16% vs 15%), ALT increased (13% and 15% vs 9%), diarrhea (13% and 14% vs 8%), alopecia (10% and 13% vs 5%), and nausea (8% and 11% vs 7%).

Drug Interactions: Monitor patients when teriflunomide is coadministered with warfarin, or with drugs metabolized by CYP1A2, CYP2C8, substrates of OAT3 transporters, substrates of BCRP, or OATP1B1/1B3 transporters.

Use in Specific Populations: Females of reproductive potential who wish to become pregnant should undergo an accelerated elimination procedure. Use of effective contraception should be continued until plasma concentrations of teriflunomide are <0.02 mcg/mL. It is not known whether AUBAGIO is excreted in human milk. AUBAGIO is detected in human semen. To minimize any possible fetal risk, men not wishing to father a child and their female partners should use effective contraception. Men wishing to father a child should discontinue therapy and either undergo accelerated elimination or verify plasma teriflunomide concentration is <0.02 mcg/mL.

Please see Full Prescribing Information, including boxed WARNING, and Medication Guide for further information.

References:
  1. AUBAGIO (teriflunomide) [package insert]. Cambridge, MA: Genzyme Corporation; November 2016.
  2. Data on file, Sanofi/Genzyme. Summary of safety HMR1726-teriflunomide. December 5, 2013.
  3. O’Connor P, Wolinsky JS, Confavreux C, et al; for the TEMSO Trial Group. Randomized trial of oral teriflunomide for relapsing multiple sclerosis. N Engl J Med. 2011;365(14):1293-1303.
  4. Confavreux C, O’Connor P, Comi G, et al; for the TOWER Trial Group. Oral teriflunomide for patients with relapsing multiple sclerosis (TOWER): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2014;13(3):247-256.
  5. Data on file, Sanofi/Genzyme. Clinical study report HMR1726-EFC10531-teriflunomide. July 31, 2012.
  6. Miller AE, Wolinsky JS, Kappos L, et al; for the TOPIC Study Group. Oral teriflunomide for patients with a first clinical episode suggestive of multiple sclerosis (TOPIC): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Neurol. 2014;13(10):977-986.
  7. O’Connor P, Wolinsky JS, Confavreux C, et al; for the TEMSO Trial Group. Randomized trial of oral teriflunomide for relapsing multiple sclerosis [supplement]. N Engl J Med. 2011;365(14):1293-1303, 1-41. http://www.nejm.org/doi/suppl/10.1056/NEJMoa1014656/suppl_file/ nejmoa1014656_appendix.pdf. Accessed August 23, 2017.
  8. O’Connor PW, Li D, Freedman MS, et al; on behalf of the Teriflunomide Multiple Sclerosis Trial Group; University of British Columbia MS/MRI Research Group. A phase II study of the safety and efficacy of teriflunomide in multiple sclerosis with relapses. Neurology. 2006;66(6):894-900.