A two-year, randomized, double-blind, placebo-controlled study involving 1,234 patients with relapsing-remitting multiple sclerosis (RRMS).2
Dosing:Patients were randomized to receive dimethyl fumarate (DMF) 240 mg twice a day (n=410), DMF 240 mg thrice a day (n=416), or placebo (n=408) for up to two years.
Age:The median age was 39 years, median time since diagnosis was four years, and median EDSS score at baseline was 2.
Endpoints:• (Primary endpoint) Proportion of patients relapsed (PPR) at two years
• Number of new or newly enlarging T2 hyperintense lesions
• Number of new T1 hypointense lesions
• Number of gadolium-enhancing (Gd+) lesions
• Annualized relapse rate (ARR)
• Confirmed disability progression
DMF reduced the risk and frequency of relapse and disability progression.
DEFINECONFIRM
Relative risk reduction in PPR at 2 years▼ 49%
Placebo: 46%; DMF: 27% (P<0.0001)		▼ 34%
Placebo: 41%; DMF: 29% (P<0.0020)
Relative reduction in ARR at 2 years▼ 53%
Placebo: 0.364; DMF: 0.172 (P<0.0001)		▼ 44%
Placebo: 0.401; DMF: 0.224 (P<0.0001)
Relative risk reduction in disability progression▼ 38%
Placebo: 27%; DMF: 16% (P<0.0050)		▼ 21%
Placebo: 17%; DMF: 14% Not statistically significant (P=0.25)
Relative risk reduction in PPR at 2 years
DEFINECONFIRM
▼ 49%
Placebo: 46%; DMF: 27% (P<0.0001)		▼ 34%
Placebo: 41%; DMF: 29% (P<0.0020)
Relative reduction in ARR at 2 years
DEFINECONFIRM
▼ 53%
Placebo: 0.364; DMF: 0.172 (P<0.0001)		▼ 44%
Placebo: 0.401; DMF: 0.224 (P<0.0001)
Relative risk reduction in disability progression
DEFINECONFIRM
▼ 38%
Placebo: 27%; DMF: 16% (P<0.0050)		▼ 21%
Placebo: 17%; DMF: 14% Not statistically significant (P=0.25)
The DMF-treated group had reduced new lesion formation and enlargement.2,3
Graphic depicting percentage of subjects with no new or newly enlarging lesions.
A two-year, multicentered, randomized, double-blind, placebo-controlled study that also included an open-label comparator arm in patients with RRMS.3
Dosing:Patients were randomized to receive DMF 240 mg twice a day (n=359), DMF 240 mg thrice a day (n=345), an open-label comparator (n=350), or placebo (n=363) for up to two years.
Age:The median age was 37 years, median time since diagnosis was three years, and median EDSS score at baseline was 2.5.
Endpoints:• (Primary endpoint) ARR at two years
• Number of new or newly enlarging T2 hyperintense lesions
• Number of new T1 hypointense lesions
• Number of Gd+ lesions
• PPR
• Confirmed disability progression
DMF reduced the risk and frequency of relapse and disability progression.
DEFINECONFIRM
Relative risk reduction in PPR at 2 years▼ 49%
Placebo: 46%; DMF: 27% (P<0.0001)		▼ 34%
Placebo: 41%; DMF: 29% (P<0.0020)
Relative reduction in ARR at 2 years▼ 53%
Placebo: 0.364; DMF: 0.172 (P<0.0001)		▼ 44%
Placebo: 0.401; DMF: 0.224 (P<0.0001)
Relative risk reduction in disability progression▼ 38%
Placebo: 27%; DMF: 16% (P<0.0050)		▼ 21%
Placebo: 17%; DMF: 14% Not statistically significant (P=0.25)
Relative risk reduction in PPR at 2 years
DEFINECONFIRM
▼ 49%
Placebo: 46%; DMF: 27% (P<0.0001)		▼ 34%
Placebo: 41%; DMF: 29% (P<0.0020)
Relative reduction in ARR at 2 years
DEFINECONFIRM
▼ 53%
Placebo: 0.364; DMF: 0.172 (P<0.0001)		▼ 44%
Placebo: 0.401; DMF: 0.224 (P<0.0001)
Relative risk reduction in disability progression
DEFINECONFIRM
▼ 38%
Placebo: 27%; DMF: 16% (P<0.0050)		▼ 21%
Placebo: 17%; DMF: 14% Not statistically significant (P=0.25)
The DMF-treated group had reduced new lesion formation and enlargement.2,3
Graphic depicting percentage of subjects with no new or newly enlarging lesions.
A long-term extension study assessing DMF efficacy and safety up to 13 years in patients with RRMS who previously participated in DEFINE and CONFIRM.4
Dosing:Patients who completed DEFINE or CONFIRM were enrolled into the ENDORSE extension study (n=1,736). They were initially kept on the same dose as per the original trial they took part in – either twice daily (BID) or three times daily (TID) – before re-randomizing after 2 years. Following the market authorization of DMF in 2013, all patients receiving DMF TID were transitioned to BID.

Overall, patients received DMF 240 mg either continuously (DMF/DMF, n=501) or after switching from placebo (PBO/DMF, n=249), with follow-up of up to 13 years.
Age:The mean age was 39.8 years, mean time since diagnosis was 6.7 years, and mean EDSS score was 2.5.
Endpoints:• Annualized relapse rate (ARR) over time
• Proportion of patients relapsed (PPR)
• MRI outcomes (including new or enlarging T1, T2 and Gd+ lesions)
• Confirmed disability worsening (CDW)
Clinical efficacy in the newly diagnosed population

Relapse rates in newly diagnosed patients were consistent with the overall patient population. In newly diagnosed patients who transitioned from placebo to DMF, model-based ARR decreased from 0.25 (95% CI, 0.17-0.36) during years 0-2 to 0.09 (95% CI, 0.06-0.13) during years 3-10, corresponding to a 64% reduction in ARR (rate ratio, 0.36 [95% CI, 0.24-0.55]; p<0.0001).4

ARR was reduced by 64% through year 10 in newly diagnosed patients who received placebo during years 0-2 and DMF during years 3-10.4
Clinical efficacy in the overall patient population

Patients who transitioned from placebo to DMF experienced a 56% reduction in ARR following DMF initiation, with the model-based ARR (95% CI) decreasing from 0.35 (0.29–0.43) during years 0–2 (DEFINE/CONFIRM) to 0.15 (0.12–0.19) during years 3–10 (ENDORSE) (rate ratio, 0.44 [95% CI, 0.34–0.56]; p<0.0001).4

Low rates of disability progression maintained over 10 years4

At year 10, 72% of continuously treated patients remained free from CDW.4 Mean EDSS scores remained low throughout follow-up.4

Patients who transitioned from placebo to DMF also maintained long-term disease control4

Mean EDSS scores remained low after approximately 8 years of DMF treatment, and most patients remained free from CDW through year 10 (81% DMF/DMF; 75% PBO/DMF).4

Stability analysis
Relapse
~75% of patients were relapse-free within the first 2 years of DMF BID treatment.4
63% of patients were relapse-free in subsequent years (up to 12 years).4
Disability progression
~92% of patients had no CDW progression during the first 2 years of DMF BID treatment.4
References

1. BAFIERTAM. Prescribing Information. Banner Life Sciences LLC.

2. Gold R, Kappos L, Arnold DL, et al. 2012. Placebo-controlled phase 3 study of oral BG-12 for relapsing multiple sclerosis. N Engl J Med. 367(12):1098-1107. doi:10.1056/NEJMoa1114287.

3. Fox RJ, Miller DH, Phillips JT, et al. 2012. Placebo-controlled phase 3 study of oral BG-12 or glatiramer in multiple sclerosis. N Engl J Med. 367(12):1087-1097. doi:10.1056/NEJMoa1206328.

4. Gold, R., et al, (2021). Long-term safety and efficacy of dimethyl fumarate for up to 13 years in patients with relapsing-remitting multiple sclerosis: Final ENDORSE study results. Multiple Sclerosis Journal, doi: https://doi.org/10.1177/13524585211037909.

Tecfidera® is a registered trademark of Biogen Inc.

Indication and Important Safety Information
Indication and Important Safety Information
Indications

BAFIERTAM® is indicated for the treatment of relapsing forms of multiple sclerosis (MS), to include clinically isolated syndrome, relapsing-remitting disease, and active secondary progressive disease, in adults.

Contraindications

BAFIERTAM is contraindicated in patients

  • With known hypersensitivity to monomethyl fumarate, dimethyl fumarate, diroximel fumarate, or to any of the excipients of BAFIERTAM. Reactions may include anaphylaxis or angioedema.
  • Taking dimethyl fumarate or diroximel fumarate.

Important Safety Information

Warnings and Precautions

Anaphylaxis and Angioedema

  • BAFIERTAM can cause anaphylaxis and angioedema after the first dose or at any time during treatment. Signs and symptoms in patients taking dimethyl fumarate (the prodrug of BAFIERTAM) have included difficulty breathing, urticaria, and swelling of the throat and tongue. Patients should be instructed to discontinue BAFIERTAM and seek immediate medical care should they experience signs and symptoms of anaphylaxis or angioedema.

Progressive Multifocal Leukoencephalopathy (PML)

  • PML has occurred in patients with MS treated with dimethyl fumarate (the prodrug of BAFIERTAM). PML is an opportunistic viral infection of the brain caused by the JC virus (JCV) that typically only occurs in patients who are immunocompromised, and that usually leads to death or severe disability. A fatal case of PML occurred in a patient who received dimethyl fumarate (the prodrug of BAFIERTAM) for 4 years while enrolled in a clinical trial.
  • PML has also occurred in patients taking dimethyl fumarate in the postmarketing setting in the presence of lymphopenia (<0.9 x 10⁹/L). While the role of lymphopenia in these cases is uncertain, the PML cases have occurred predominantly in patients with lymphocyte counts <0.8 x 10⁹/L persisting for more than 6 months.
  • At the first sign or symptom suggestive of PML, withhold BAFIERTAM and perform an appropriate diagnostic evaluation. Typical symptoms associated with PML are diverse, progress over days to weeks, and include progressive weakness on one side of the body or clumsiness of limbs, disturbance of vision, and changes in thinking, memory, and orientation leading to confusion and personality changes.
  • Magnetic resonance imaging (MRI) findings may be apparent before clinical signs or symptoms. Monitoring with MRI for signs consistent with PML may be useful, and any suspicious findings should prompt further investigation for early diagnosis, if present.

Herpes Zoster and Other Serious Opportunistic Infections

  • Serious cases of herpes zoster have occurred with dimethyl fumarate (the prodrug of BAFIERTAM), including disseminated herpes zoster, herpes zoster ophthalmicus, herpes zoster meningoencephalitis, and herpes zoster meningomyelitis. These events may occur at any time during treatment. Monitor patients on BAFIERTAM for signs and symptoms of herpes zoster. If herpes zoster occurs, appropriate treatment for herpes zoster should be administered.
  • Other serious opportunistic infections have occurred with dimethyl fumarate (the prodrug of BAFIERTAM), including cases of serious viral (herpes simplex virus, West Nile virus, cytomegalovirus), fungal (Candida and Aspergillus), and bacterial (Nocardia, Listeria monocytogenes, Mycobacterium tuberculosis) infections. These infections have been reported in patients with reduced absolute lymphocyte counts (ALC) as well as in patients with normal ALC. These infections have affected the brain, meninges, spinal cord, gastrointestinal tract, lungs, skin, eye, and ear. Patients with symptoms and signs consistent with any of these infections should undergo prompt diagnostic evaluation and receive appropriate treatment.
  • Consider withholding BAFIERTAM treatment in patients with herpes zoster or other serious infections until the infection has resolved.

Lymphopenia

  • BAFIERTAM may decrease lymphocyte counts. Prolonged, severe lymphopenia (lymphocyte counts <0.5 × 10⁹/L for ≥6 months) has been reported with dimethyl fumarate (the prodrug of BAFIERTAM), and recovery after discontinuation may be delayed.
  • Obtain a complete blood count (CBC), including lymphocyte count, before initiating treatment with BAFIERTAM, at 6 months after initiation, and then every 6 to 12 months thereafter, and as clinically indicated. Consider interruption of BAFIERTAM in patients with lymphocyte counts <0.5 × 10⁹/L persisting for more than 6 months. Continue to monitor lymphocyte counts until recovery if BAFIERTAM is discontinued or interrupted because of lymphopenia. Consider withholding treatment in patients with serious infections until resolution. Decisions to restart BAFIERTAM should be individualized.

Liver Injury

  • Clinically significant cases of liver injury have been reported in the postmarketing setting with dimethyl fumarate (the prodrug of BAFIERTAM), with onset ranging from a few days to several months after treatment initiation. Findings have included elevations of serum aminotransferases (>5× ULN) and total bilirubin (>2× ULN). Some cases required hospitalization, and abnormalities resolved following treatment discontinuation. The combination of new aminotransferase elevations with increased bilirubin levels is an important predictor of serious drug‑induced liver injury.
  • Obtain serum aminotransferase, alkaline phosphatase, and total bilirubin levels before initiating BAFIERTAM and during treatment, as clinically indicated. Discontinue BAFIERTAM if clinically significant liver injury induced by BAFIERTAM is suspected.

Flushing

  • BAFIERTAM may cause flushing (e.g., warmth, redness, itching, and/or burning sensation). In clinical trials of dimethyl fumarate (the prodrug of BAFIERTAM), flushing was reported in approximately 40% of patients, generally occurring soon after treatment initiation and typically improving or resolving over time. In most patients, flushing was mild to moderate in severity. Administration of non-enteric coated aspirin (up to 325 mg) approximately 30 minutes prior to dosing may reduce the incidence or severity of flushing.

Serious Gastrointestinal Reactions

  • Serious gastrointestinal reactions, including perforation, ulceration, hemorrhage, and obstruction, some with fatal outcomes, have been reported in the postmarketing setting with the use of fumaric acid esters, including dimethyl fumarate, with or without concomitant aspirin use. The majority of these events have occurred within 6 months of fumaric acid ester treatment initiation. In controlled clinical trials, the incidence of serious gastrointestinal adverse events was 1% in patients treated with dimethyl fumarate; these events, none of which were fatal, included vomiting (0.3%) and abdominal pain (0.3%).
  • Monitor patients, promptly evaluate, and discontinue BAFIERTAM for new or worsening severe gastrointestinal signs and symptoms.

Adverse Reactions

  • The most common adverse reactions reported with dimethyl fumarate (the prodrug of BAFIERTAM) were flushing and gastrointestinal-related events (e.g., nausea, vomiting, diarrhea, abdominal pain, and dyspepsia). Gastrointestinal events generally occurred early in treatment and often decreased over time.
  • A transient increase in mean eosinophil counts was observed during the first 2 months of treatment.

For more detailed information, please refer to the full Prescribing Information here.

To report SUSPECTED ADVERSE REACTIONS, contact Banner Life Sciences at toll free phone: 1-866-MMF-95MG or the FDA at: 1-800-FDA-1088 or www.fda.gov/medwatch.

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US-MMF-2600136 | July 2026