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

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

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... 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

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

Retrospective review of lymphocyte changes when switching between fumarates in patients with multiple sclerosis. (PubMed, Mult Scler Relat Disord) - "Our study demonstrated that patients switched to DRF had a significantly lower ALC at follow-up and were more likely to have lymphopenia compared to patients switched to MMF."

Journal • Retrospective data • CNS Disorders • Multiple Sclerosis

Diroximel Fumarate-Loaded Solid Lipid Nanoparticles (DRF-SLNs) as Potential Carriers for the Treatment of Multiple Sclerosis: Preformulation Study. (PubMed, Int J Mol Sci) - "Interactions between SLNs and biomembrane models (MLV) were also studied to elucidate their cellular uptake mechanism. Future work will focus on evaluating the in vivo efficacy of this novel nanoformulation."

Journal • CNS Disorders • Gastrointestinal Disorder • Multiple Sclerosis

Effect of diroximel fumarate on gut dysbiosis and autoimmunity in the central nervous system. (PubMed, Int Immunopharmacol) - "Furthermore, DRF reduced the production of CCL22, a chemokine derived from macrophages. Overall, our findings suggest that DRF can reduce neuroinflammation by lowering the production of IL-17, inhibiting the development of α4β1 + CD4+ T cells and α4β7 + CD4+ T cells in the lymph nodes, and alleviating dysfunction associated with gut dysbiosis and intestinal permeability."

Journal • CNS Disorders • Immunology • Inflammation • Multiple Sclerosis • CCL2 • CCL22 • CD4 • IL17A • LCN2

Cellular and humoral vaccination response under immunotherapies-German consensus on vaccination strategies in neurological autoimmune diseases. (PubMed, Ther Adv Neurol Disord) - "The specific humoral and cellular response to vaccination can be compromised under alemtuzumab, azathioprine, cladribine, cyclophosphamide, CD19/CD20 antibodies (inebilizumab, ocrelizumab, ofatumumab, rituximab, ublituximab), dimethyl fumarate/diroximel fumarate, FcRn inhibitors (efgartigimod, rozanolixizumab), complement C5 inhibitors (eculizumab, ravulizumab, zilucoplan), interleukin-6 receptor antibodies (tocilizumab, satralizumab), intravenous immunoglobulins, long-term steroid administration, methotrexate, mitoxantrone, mycophenolate mofetil, tacrolimus, teriflunomide, tumor necrosis factor-α blockers, and sphingosine-1-phosphate receptor modulators (fingolimod, ozanimod, ponesimod, siponimod), as well as after autologous stem cell transplantation...However, the humoral and cellular vaccination response may be impaired under immunotherapy necessitating close monitoring. Here, we provide applicable recommendations to optimize immunization for individuals receiving..."

Journal • CNS Disorders • Immunology • Infectious Disease • Oncology • Transplantation • IL6R

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