Vumerity (diroximel fumarate) / Biogen, Alkermes - LARVOL DELTA

TREAT-MS: Traditional Versus Early Aggressive Therapy for Multiple Sclerosis Trial (clinicaltrials.gov) - P=N/A | N=900 | Completed | Sponsor: Johns Hopkins University | Active, not recruiting ➔ Completed

Trial completion • CNS Disorders • Multiple Sclerosis

Predictors of high- versus low-intensity first-line multiple sclerosis treatments. (PubMed, Mult Scler J Exp Transl Clin) - "The first DMT filled was classified as either high- (natalizumab, alemtuzumab, ocrelizumab, rituximab, ofatumumab, cladribine) or low-intensity (interferon, glatiramer acetate, teriflunomide, dimethyl fumarate, diroximel fumarate, fingolimod, ponesimod, siponimod, ozanimod)...The minority of MS patients initiated high-intensity treatment although this proportion increased over time, and later years were predictive of high-intensity treatment. Providers had a significant role in the approach selected."

Journal • CNS Disorders • Multiple Sclerosis

Comparative multi-analyte serum protein differences between generic and brand-name dimethyl fumarate, fingolimod, and teriflunomide in multiple sclerosis. (PubMed, Clin Immunol) - "We compared biomarker variability in MS individuals (n = 1124) treated with generic or brand-name fumarates (diroximel fumarate, dimethyl fumarate (DMF)), fingolimod, and teriflunomide...Additionally, all generic DMTs demonstrated higher multi-variable variability index values across 18 proteins associated with MS disease activity. Greater biomarker variability with generic formulations may reflect differences in therapeutic exposure and less consistent disease control."

Journal • CNS Disorders • Multiple Sclerosis • CCL20 • CXCL13 • CXCL9 • TNFSF13B

Diroximel fumarate confers neuroprotection via reduced Th1 responses and induction of the anti-oxidative Nrf2 pathway in experimental neuroinflammation. (PubMed, PLoS One) - "Peripheral immune cells from DRF-treated mice produced lower levels of IFN-γ and IL-17A, while Nrf2-dependent antioxidative genes were upregulated in CNS tissue. Our results demonstrate neuroprotective, immunomodulatory, and antioxidative effects of DRF, supporting its role as beneficial modulator in neuroinflammation."

Journal • CNS Disorders • Immunology • Inflammation • Multiple Sclerosis • IFNG • IL17A

Structure-Property Relationship Analysis of α-Keto Ester Prodrugs of Monomethyl Fumarate as NRF2 Activators. (PubMed, ACS Chem Neurosci) - "While activation of NRF2 by monomethyl fumarate (MMF) is well established, the systemic exposure and broad side-effect profile of MMF and its two FDA-approved prodrugs, diroximel fumarate and dimethyl fumarate, limit their broader therapeutic utility...Specifically, α-keto esters 4, 5, and 6, functionalized with trideutero methyl, ethyl, and iso-propyl esters, respectively, exhibit strong tissue-specific NRF2 activation in vivo, where 4 demonstrated full reversal of mechanical allodynia in a mouse model of neuropathy. These findings firmly establish α-keto ester prodrugs of MMF as a next-generation NRF2-targeting modality that overcomes the systemic exposure and off-target liabilities of existing fumarate therapies by exploiting pathological ROS as a trigger."

Journal • Pain

Impact of Nrf2 Activation on Macrovascular, Microvascular & Leg Function & Walking Capacity in Peripheral Artery Disease (clinicaltrials.gov) - P1 | N=20 | Recruiting | Sponsor: University of Nebraska | Trial completion date: Aug 2026 ➔ Dec 2026 | Trial primary completion date: Aug 2026 ➔ Dec 2026

Trial completion date • Trial primary completion date • Cardiovascular • Peripheral Arterial Disease

A Study to Learn More About The Safety of Diroximel Fumarate (VUMERITY®) in Participants Who Took it During Pregnancy And About the Health of Their Babies (clinicaltrials.gov) - P=N/A | N=1178 | Active, not recruiting | Sponsor: Biogen | Recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Multiple Sclerosis

Infection and Relapse Outcomes In People with MS Transitioning from Standard Interval Dosed Anti-CD20 Therapies to Fumarates or to Extended Interval Dosed Anti-CD20s (CMSC 2026) - " PwMS (age 18-64 y) were identified retrospectively from 01 Jan 2017 to 31 Dec 2023 in the Komodo Health claims database who had initiated FUM (dimethyl fumarate or diroximel fumarate) or EID anti-CD20 (ocrelizumab [OCR) or ofatumumab (OFA)... Annualized infection rates were significantly lower for PwMS transitioning from anti-CD20 to FUM compared with PwMS transitioning from SID to EID anti-CD20s. Transitioning from anti-CD20s to FUM was also associated with a lower ARR compared to extending the dosing interval with the anti-CD20; this finding warrants further investigation but does suggest that transitioning to FUM may have at least similar effectiveness as anti-CD20 EID in controlling relapses. Study Support: Biogen"

CNS Disorders • Multiple Sclerosis

Comparative Effectiveness of Diroximel Fumarate Versus Dimethyl Fumarate In Persons with Multiple Sclerosis: A US Claims Analysis of Relapse Outcomes (CMSC 2026) - "The results of this real-world analysis indicate DRF may be more effective than DMF in reducing relapses over 1 and 2 years of treatment in pwMS. These findings warrant further investigation but suggest the improved tolerability profile of DRF versus DMF may contribute to improved real-world effectiveness for pwMS. Study Support: Biogen."

HEOR • Late-breaking abstract • CNS Disorders • Multiple Sclerosis

Comparative Effectiveness of Diroximel Fumarate vs. Dimethyl Fumarate in Persons with Multiple Sclerosis: A US Claims Analysis of Relapse Outcomes. (PubMed, Adv Ther) - "The results of this real-world analysis indicate DRF may be more effective than DMF in reducing relapses over 1 and 2 years of treatment in pwMS."

HEOR • Journal • CNS Disorders • Multiple Sclerosis

DARLENE: DIROXIMEL FUMARATE TO REDUCE PERIHAEMATOMAL OEDEMA IN INTRACEREBRAL HAEMORRHAGE: DOUBLE BLIND RANDOMIZED CLINICAL TRIAL (clinicaltrials.gov) - P2 | N=192 | Recruiting | Sponsor: University Hospital, Lille | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular

A Comparative Effectiveness Analysis of Fumarates versus Cladribine in People With MS Transitioning From Anti-CD20 Therapies (AAN 2026) - "Strategies to mitigate risks with anti-CD20s include switching to oral DMTs such as FUM (dimethyl fumarate; diroximel fumarate) or oral CLAD...Additional results will be presented. Conclusions These results indicate that relapse rates were comparable between FUM and CLAD and suggest FUM may be as effective as CLAD in controlling disease activity in PwMS transitioning from anti-CD20 therapies."

HEOR • CNS Disorders • Infectious Disease • Multiple Sclerosis

VOYAGE: A Study to Learn About the Safety of Diroximel Fumarate (DRF) and Dimethyl Fumarate (DMF) and Their Effects on Relapses in Pediatric Participants With Relapsing Forms of Multiple Sclerosis (RMS) (clinicaltrials.gov) - P3 | N=185 | Not yet recruiting | Sponsor: Biogen

New P3 trial • CNS Disorders • Multiple Sclerosis • Pediatrics

Appendicitis and multiple sclerosis disease-modifying therapies: a disproportionality analysis of the FDA adverse event reporting system. (PubMed, Mult Scler Relat Disord) - "Patient counseling on early appendicitis warning signs and indications for urgent evaluation may be warranted for people with MS on DMTs."

Adverse events • Journal • CNS Disorders • Gastroenterology • Gastrointestinal Disorder • Multiple Sclerosis

AIOLOS: A NIS Evaluating Various Injectable and Oral Treatments in Patients With Relapsing Multiple Sclerosis (clinicaltrials.gov) - P=N/A | N=800 | Recruiting | Sponsor: Novartis Pharmaceuticals | N=1214 ➔ 800

Enrollment change • CNS Disorders • Multiple Sclerosis • IFNB1

2024_0474: DIROXIMEL FUMARATE TO REDUCE PERIHAEMATOMAL OEDEMA IN INTRACEREBRAL HAEMORRHAGE: A DOUBLE BLIND RANDOMIZED CLINICAL TRIAL (clinicaltrialsregister.eu) - P2/3 | N=192 | Not yet recruiting | Sponsor: Centre Hospitalier Universitaire De Lille

New P2/3 trial • Cardiovascular

A Study to Learn About the Safety of BIIB091 and Its Effect on Brain Inflammation When Taken Alone or With Diroximel Fumarate (DRF) in Adults With Relapsing Forms of Multiple Sclerosis (MS) (clinicaltrials.gov) - P2 | N=127 | Completed | Sponsor: Biogen | Terminated ➔ Completed

Monotherapy • Trial completion • CNS Disorders • Inflammation • Multiple Sclerosis

A Study to Learn About the Safety of BIIB091 and Its Effect on Brain Inflammation When Taken Alone or With Diroximel Fumarate (DRF) in Adults With Relapsing Forms of Multiple Sclerosis (MS) (clinicaltrials.gov) - P2 | N=127 | Terminated | Sponsor: Biogen | Trial completion date: Sep 2027 ➔ Feb 2026 | Active, not recruiting ➔ Terminated | Trial primary completion date: Sep 2027 ➔ Feb 2026

Monotherapy • Trial completion date • Trial primary completion date • Trial termination • CNS Disorders • Inflammation • Multiple Sclerosis

Comparative Effectiveness and Risk of Severe Infection in Adult Patients With MS Treated With Diroximel Fumarate Versus Anti-CD20 Monoclonal Antibodies: A Real-World Claims Analysis. (PubMed, Adv Ther) - "DRF-treated patients with MS had a significantly lower risk of SI compared with anti-CD20-treated patients, with no difference in ARR. More real-world studies are needed to understand the efficacy and safety of DMTs in the setting of de-escalation in aging patients with MS."

HEOR • Journal • Real-world evidence • CNS Disorders • Infectious Disease • Multiple Sclerosis • Novel Coronavirus Disease

AIOLOS: A NIS Evaluating Various Injectable and Oral Treatments in Patients With Relapsing Multiple Sclerosis (clinicaltrials.gov) - P=N/A | N=1214 | Recruiting | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Recruiting | N=564 ➔ 1214 | Trial completion date: Dec 2026 ➔ May 2029 | Trial primary completion date: Dec 2026 ➔ May 2029

Enrollment change • Enrollment open • Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis • IFNB1

FORTUNE: Investigating the Effect of Diroximel Fumarate on Glutathione in Schizophrenia (clinicaltrials.gov) - P=N/A | N=30 | Recruiting | Sponsor: King's College London | Trial completion date: Jun 2026 ➔ Jan 2027 | Trial primary completion date: Mar 2026 ➔ Jan 2027

Trial completion date • Trial primary completion date • CNS Disorders • Psychiatry • Schizophrenia

A Comparative Effectiveness Analysis of Fumarates versus Cladribine in People with MS Transitioning from Anti-CD20 Therapies (ACTRIMS Forum 2026) - "Strategies to mitigate risks with anti-CD20 include switching to oral DMTs such as a fumarate (FUM; dimethyl fumarate; diroximel fumarate) or oral cladribine (CLAD)... These results indicate that relapse rates were comparable between FUM and CLAD and suggest FUM may be as effective as CLAD in controlling disease activity in PwMS transitioning from anti-CD20 therapies.Study Supported by: Biogen"

HEOR • CNS Disorders • Infectious Disease • Multiple Sclerosis

Relapse and Infection Outcomes in People with Multiple Sclerosis Treated with Diroximel Fumarate Versus Anti-CD20 Therapy Using Extended Interval Dosing (ACTRIMS Forum 2026) - "Background & Objectives: Long-term treatment with anti-CD20 monoclonal antibodies (anti-CD20s), such as ocrelizumab (OCR), in people with multiple sclerosis (PwMS) can lead to increased infection risks and lowered vaccine response due to impacted humoral immune response when compared to treatment with other disease modifying therapies (DMTs). With some MS DMTs, such as natalizumab, extending the dosing interval between infusions (referred to as extended interval dosing, or EID) has been shown to mitigate these risks... These results indicate that annualized infection rates are lower with DRF compared to PwMS transitioning from SID- to EID-OCR and suggest infection rates may be higher with prolonged B-cell depletion regardless of OCR dosing cadence. ARR was similar for DRF vs SID-OCR and EID-OCR.Study Supported by: Biogen"

CNS Disorders • Infectious Disease • Multiple Sclerosis

Biogen reports strong fourth quarter and full year 2025 results and provides full year 2026 financial guidance (Biogen Press Release) - "LEQEMBI fourth quarter global in-market sales of approximately $134 million, up 54% year-over-year, with U.S. in-market sales of approximately $78 million, representing continued growth; SKYCLARYS grew global patients on therapy by approximately 30% in 2025; fourth quarter U.S. revenue of approximately $89 million driven by demand growth, with ex-U.S. revenue of approximately $44 million reflecting continued demand growth, also impacted by a one-time reimbursement true-up; ZURZUVAE fourth quarter revenue of approximately $66 million showed strong continued demand growth; VUMERITY grew 3% year-over-year in the fourth quarter; SPINRAZA fourth quarter revenue declined 15% year-over-year, impacted by timing of shipments outside the U.S., with full year revenue down 2% year-over-year."

Commercial • Alzheimer's Disease • Depression • Friedreich ataxia • Multiple Sclerosis • Muscular Atrophy • Ocular Inflammation • Pain • Parkinson's Disease

A Study to Learn About the Safety of BIIB091 and Its Effect on Brain Inflammation When Taken Alone or With Diroximel Fumarate (DRF) in Adults With Relapsing Forms of Multiple Sclerosis (MS) (clinicaltrials.gov) - P2 | N=127 | Active, not recruiting | Sponsor: Biogen | Recruiting ➔ Active, not recruiting | N=275 ➔ 127

Enrollment change • Enrollment closed • Monotherapy • CNS Disorders • Inflammation • Multiple Sclerosis