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

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

New P2 trial • Cardiovascular

STHENOS: Open Label Randomized Multicenter to Assess Efficacy & Tolerability of Ofatumumab 20mg vs. First Line DMT in RMS (clinicaltrials.gov) - P3 | N=185 | Completed | Sponsor: Novartis Pharmaceuticals | Active, not recruiting ➔ Completed | Trial completion date: Feb 2026 ➔ Nov 2025

Trial completion • Trial completion date • CNS Disorders • Multiple Sclerosis

Zydus Lifesciences receives USFDA approval for Diroximel Fumarate delayed-release capsules (ExpressPharma) - "Diroximel Fumarate delayed-release capsules, 231 mg, are indicated for the treatment of relapsing forms of multiple sclerosis (MS) in adults. The capsules will be produced at Zydus Lifesciences, SEZ....According to IQVIA MAT data for September 2025, Diroximel Fumarate delayed-release capsules had annual sales of USD 999.4 million in the United States."

ANDA • Sales • Multiple Sclerosis

Fumarate-based drugs protect against neuroinflammation via upregulation of anti-ferroptotic pathways. (PubMed, J Neuroinflammation) - "Fumarates, dimethyl fumarate (DMF) and its successor diroximel fumarate (DRF), are approved disease modifying therapies for multiple sclerosis and activate the Nrf2 pathway regulating the expression of many antioxidative enzymes...This effect is absent in primary fibroblasts derived from osteo- or rheumatoid arthritis patients. In summary, our data offer a new organ- and disease-specific molecular anti-inflammatory mechanism of DRF."

Journal • CNS Disorders • Immunology • Inflammation • Inflammatory Arthritis • Multiple Sclerosis • Rheumatoid Arthritis • Rheumatology • Solid Tumor

A Study of Diroximel Fumarate (DRF) in Adult Participants From the Asia-Pacific Region With Relapsing Forms of Multiple Sclerosis (RMS) (clinicaltrials.gov) - P3 | N=136 | Completed | Sponsor: Biogen | N=102 ➔ 136

Enrollment change • CNS Disorders • Multiple Sclerosis

Transition from anti-CD20 therapies to fumarates as a treatment strategy: A multicenter, retrospective observational experience. (PubMed, Mult Scler J Exp Transl Clin) - "Tolerability was the main reason for discontinuing fumarates. Future studies will provide additional insight into how to effectively and safely transition from anti-CD20s to fumarates."

Journal • Retrospective data • CNS Disorders • Infectious Disease • Multiple Sclerosis

Patient and healthcare provider experience of diroximel fumarate: considerations for selecting disease-modifying therapy. (PubMed, Neurodegener Dis Manag) - "A real-world, patient-focused survey on MS treatment suggested DRF was well tolerated and associated with patient-reported physical benefits. HCP-reported reasons for selecting DRF included efficacy and tolerability issues with prior DMT."

Journal • CNS Disorders • Multiple Sclerosis

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 2025 ➔ Aug 2026 | Trial primary completion date: Aug 2025 ➔ Aug 2026

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

Use of disease-modifying therapies in France from 2017 to 2023 (ECTRIMS 2025) - "DMTs were identified using specific codes and classified as: very-high-efficacy (natalizumab, rituximab, ocrelizumab, ofatumumab), high-efficacy (fingolimod, ponesimod, cladribine), moderate efficacy (beta interferon, glatiramer acetate, dimethyl fumarate, diroximel fumarate, teriflunomide), and an off-label category (methotrexate, mycophenolate mofetil, azathioprine, cyclophosphamide)... From 2017 to 2023, DMT use among PwMS in France increased, with a marked rise in very high-efficacy therapies, including as first treatment. While proportions were similar across sexes and socioeconomic levels, geographic disparities, especially in anti-CD20 use, persisted, highlighting the need to ensure equitable access to care."

Long-Term Treatment with Fumarates versus Anti-CD20 Monoclonal Antibodies and Infection-related Outcomes in Patients with Multiple Sclerosis (ECTRIMS 2025) - " The study included 1956 PS-matched PwMS, with 652 FUM initiators (614 dimethyl fumarate, 38 diroximel fumarate) and 1304 anti-CD20 initiators (1296 ocrelizumab, 8 ofatumumab)... PwMS treated with FUM experienced significantly lower long-term infection-related HCRU compared with those on anti-CD20s, with similar relapse outcomes. The difference in infection risk between FUM and anti-CD20 therapies increased with treatment duration, consistent with prior evidence that infection risk rises with long term B-cell depletion. These findings underscore the long-term risk-benefit considerations when selecting or maintaining DMTs in MS management."

Clinical • CNS Disorders • Infectious Disease • Multiple Sclerosis

Baseline Data from the FILAXOS Study: Real-World Impact of Serum Neurofilament Light Chain on Management of RMS Patients (ECTRIMS 2025) - "Based on the NfL level the decision was made to either switch to ofatumumab treatment or continue current therapy with either dimethyl fumarate/diroximel fumarate, glatiramer acetate, interferon beta or teriflunomide... These baseline data provide initial insights into MS patients in Germany who are being treated with low efficacy DMT and have undergone NfL measurements. The majority of patients remain on their low efficacy DMT upon entering the study. The course of the study will show how the therapeutic decision impacts NfL value and patient outcomes."

Clinical • Real-world • Real-world evidence • NEFL

Adverse events with Diroximel Fumarate versus Dimethyl Fumarate in Multiple Sclerosis: A Real-World Study (ECTRIMS 2025) - "Diroximel fumarate appeared to be a well-tolerated alternative to dimethyl fumarate, with a lower incidence of flushing and a similar safety profile in terms of lymphocyte counts, gastrointestinal effects and skin rash."

Adverse events • Clinical • Real-world • Real-world evidence • CNS Disorders • Dermatology • Multiple Sclerosis

Prospective De-Escalation from B-cell Depletion to Fumarates: Interim 1-year results (ECTRIMS 2025) - "Half were on ocrelizumab, 40% on rituximab, and 10% on ofatumumab. Eight patients transitioned to diroximel fumarate (DRF) and 2 to dimethyl fumarate (DMF)... De-escalating from B-cell depleting therapies to fumarates appears to maintain efficacy early in this transition. This is a two-year study that is ongoing to better evaluate efficacy and safety of this treatment switch."

Clinical • CNS Disorders • Infectious Disease • Multiple Sclerosis

Circulating MicroRNA Signatures as Potential Biomarkers for Treatment Response in Diroximel Fumarate-Treated Multiple Sclerosis Patients (ECTRIMS 2025) - "Circulating serum miRNAs show potential as biomarkers for assessing disease activity and treatment response in MS."

Biomarker • Clinical • CNS Disorders • Multiple Sclerosis • MIR122 • MIR182 • MIR191 • MIR30E • MIR320A • MIR320B • MIR484

Impact of CD20-Antibody Therapy on Serum Neurofilament Light Chain and GFAP Levels in a Prospective RRMS Cohort (ECTRIMS 2025) - P | "Objectives/Aims: Evaluating changes in sNfL and sGFAP levels in RRMS patients starting therapy with either ocrelizumab (OCR) or ofatumumab (OFA) over a period of up to 12 months, reflecting treatment response and CDA...34 patients (32.1%) had received high-efficacy therapy (HET) including natalizumab, fingolimod, alemtuzumab and cladribine. 33 patients (31.1%) were priorly treated with platform DMTs like dimethyl fumarate, diroximel fumarate, glatiramer acetate, interferon beta and teriflunomide... SNfL is a valuable biomarker for monitoring disease activity in RRMS patients. Our data demonstrates a clear reduction in sNfL levels following anti-CD20 therapy, observed consistently in treatment-naïve patients as well as in those previously treated with platform DMTs or HET. The analysis of sGFAP dynamics is ongoing and will be presented in the final study results."

Clinical • CNS Disorders • Multiple Sclerosis • GFAP • NEFL

Matching-adjusted indirect comparisons of diroximel fumarate, ocrelizumab and interferon beta-1a for relapsing multiple sclerosis. (PubMed, J Comp Eff Res) - P3 | " While there were no significant differences in clinical outcomes (ARR, 12-week CDP and 24-week CDP) observed for DRF versus OCR, radiological outcomes indicated favorability for OCR. All outcomes favored DRF over IFNβ-1a, except from new/newly enlarging T2 lesions, which showed no significant difference."

Clinical • Journal • CNS Disorders • Multiple Sclerosis • IFNB1

DELIVER-MS: Determining the Effectiveness of earLy Intensive Versus Escalation Approaches for RRMS (clinicaltrials.gov) - P4 | N=800 | Active, not recruiting | Sponsor: The Cleveland Clinic | Trial completion date: Sep 2030 ➔ Jul 2027

Trial completion date • CNS Disorders • Multiple Sclerosis

Targeted activation of Nrf2 at sites of oxidative stress reverses doxorubicin-induced cognitive impairments in mice. (PubMed, Brain Behav Immun) - "With this in mind, we tested if activation of the master regulator of antioxidant response nuclear factor E2-related factor 2 (Nrf2) using compound 1c or diroximel fumarate (DRF) would restore cognitive function after doxorubicin treatment. These results demonstrate the therapeutic potential of Nrf2 activators to reverse doxorubicin-induced cognitive impairments, and associated structural, phenotypic, and molecular changes in the hippocampus. The localized release of MMF by 1c at sites of oxidative stress has the potential to diminish unwanted effects of fumarates while reversing CICI induced by doxorubicin."

Journal • Preclinical • Alzheimer's Disease • Cognitive Disorders • Oncology • DLG4

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=275 | Recruiting | Sponsor: Biogen | Trial completion date: Nov 2026 ➔ Sep 2027 | Trial primary completion date: Jul 2025 ➔ Sep 2027

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

Comparative Effectiveness of Fumarates Versus Sphingosine-1-Phosphate Receptor Modulators in Black Patients with Multiple Sclerosis. (PubMed, Neurol Ther) - "This real-world, claims-based analysis demonstrates that fumarates and S1P receptor modulators have similar effectiveness in reducing relapses among Black PwMS, with > 72% of patients in both treatment groups remaining relapse-free at 24 months. Given the underrepresentation of Black patients in MS clinical trials, these results provide valuable real-world evidence to guide treatment decisions for this population."

HEOR • Journal • CNS Disorders • Multiple Sclerosis

Real-World Treatment Outcomes in Black, Hispanic, Asian, and White People with Multiple Sclerosis Treated with Fumarates in the USA. (PubMed, Neurol Ther) - "Consistent with prior studies, these results demonstrate the effectiveness of fumarates across racial and ethnic MS subgroups. This is the largest analysis to date of the treatment effects of any individual class of DMT in Black and Hispanic PwMS. Infographic available for this article."

HEOR • Journal • Real-world evidence • CNS Disorders • Multiple Sclerosis

Assessment of Real-World Adverse Events Associated with Ozanimod in Relapsing Remitting Multiple Sclerosis (RRMS) (ISPOR 2025) - "AE reports and patient outcomes were extracted for all instances where DMTs (ozanimod, dimethyl fumarate, monomethyl fumarate, diroximel fumarate, fingolimod, ponesimod, siponimod, teriflunomide, cladribine, alemtuzumab, natalizumab, ocrelizumab, ublituximab, and ofatumumab) were the ‘primary suspect’ for the AE... Based on this descriptive analysis of the FAERS data, ozanimod has a lower proportion of AEs linked to serious outcomes than the other DMTs. Ozanimod generally had a larger share of the ten labeled AEs compared with the other DMTs; however, these labeled AEs made up a small percentage of all the AEs reported for ozanimod and the other DMTs."

Adverse events • Clinical • Real-world • Real-world evidence • Back Pain • Cardiovascular • CNS Disorders • Hypertension • Hypotension • Infectious Disease • Multiple Sclerosis • Musculoskeletal Pain • Pain • Respiratory Diseases

FORTUNE: Investigating the Effect of Diroximel Fumarate on Glutathione in Schizophrenia (clinicaltrials.gov) - P=N/A | N=30 | Recruiting | Sponsor: King's College London

New trial • CNS Disorders • Psychiatry • Schizophrenia

Safety and effectiveness of diroximel fumarate in relapsing forms of multiple sclerosis: a systematic review and meta-analysis. (PubMed, Neurol Sci) - "DRF demonstrates efficacy in reducing relapse rates and offers an improved safety profile compared to its predecessor, Dimethyl Fumarate (DMF), particularly in GI tolerability. However, lymphopenia requires monitoring. Further research is recommended to evaluate long-term safety and efficacy in diverse populations."

Journal • Retrospective data • Review • CNS Disorders • Gastrointestinal Disorder • Multiple Sclerosis

Herpes zoster infection in a patient with relapsing-remitting multiple sclerosis treated with diroximel fumarate. (PubMed, BMJ Case Rep) - "She was diagnosed with herpes zoster, treated with valacyclovir and gabapentin, and made a full recovery. Ensuring patients are protected against varicella-zoster virus before starting diroximel fumarate can prevent this painful infection. Thus, we recommend vaccination against the varicella-zoster virus prior to diroximel fumarate initiation be incorporated as the standard of care."

Journal • CNS Disorders • Herpes Zoster • Infectious Disease • Multiple Sclerosis • Pain • Varicella Zoster