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

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

Analysis of diroximel fumarate data for patients with relapsing forms of multiple sclerosis using related adverse events from the FDA adverse reporting system. (PubMed, Expert Opin Drug Saf) - "Our study identified several potentially important AEs that were not mentioned in the DRF instructions. However, further epidemiologic studies are needed to validate these findings."

Adverse events • Journal • Breast Cancer • CNS Disorders • Multiple Sclerosis • Oncology • Ophthalmology • Solid Tumor

Herpes Zoster Infections With Multiple Sclerosis Disease-Modifying Therapies: A Real-World Pharmacovigilance Study. (PubMed, Neurol Clin Pract) - "We queried the Food and Drug Administration Adverse Event Reporting System (FAERS) and OpenVigil 2.1 for reports of HZ involving immunosuppressive MS DMTs (ocrelizumab [OCR], ofatumumab [OFT], rituximab [RTX], natalizumab [NTZ], alemtuzumab, dimethyl fumarate and diroximel fumarate [DRF], fingolimod [FING], siponimod [SIP], ozanimod [OZ], mitoxantrone [MITO], cladribine [CLAD], and teriflunomide [TERF]) and calculated reporting odds ratios and their 95% CIs...Immunosuppressive MS DMTs are associated with greater HZ reporting in the FAERS. These findings emphasize the importance of pre-DMT HZ vaccination because of avoidable HZ infections."

Adverse events • Journal • Real-world evidence • CNS Disorders • Herpes Zoster • Infectious Disease • Multiple Sclerosis • Varicella Zoster

Matching-adjusted Indirect Comparisons of Diroximel Fumarate, Ocrelizumab, and Interferon Beta-1a (AAN 2025) - P3 | "The MAIC indicated no significant differences in clinical outcomes for DRF vs OCR; radiological outcomes favoured OCR. All outcomes favoured DRF vs IFN, apart from N/NE T2 lesions."

CNS Disorders • Multiple Sclerosis

miRNAs as Biomarkers for Disease Activity and Treatment Response in Relapsing Multiple Sclerosis (ACTRIMS Forum 2025) - "Additionally, we compared baseline miRNA expression to 6 months post-treatment initiation in two patient groups: 20 receiving diroximel fumarate (DRF) and 20 treated with cladribine. This study identifies circulating serum miRNAs as potential biomarkers for monitoring disease activity and treatment response in MS. Specifically, miR-320b emerges as a promising candidate for predicting treatment outcomes."

Biomarker • CNS Disorders • Multiple Sclerosis • MIR122 • MIR15B • MIR182 • MIR191 • MIR30E • MIR320A • MIR320B • MIR326 • MIR484

Real-World Treatment Outcomes in People with Multiple Sclerosis who Switched From Teriflunomide to Fumarates (ACTRIMS Forum 2025) - "There is limited understanding of the real-world clinical disease activity and healthcare resource utilization (HRU) and healthcare costs (HCC) among pwMS who switch from teriflunomide (TERI) to fumarate (FUM; either dimethyl fumarate [DMF] or diroximel fumarate [DRF]) therapies.Objectives: To estimate pre- and post-switch annualized relapse rate (ARR), time to relapse, 1-yr pre-index vs post-index MS-related HRU and HCC in pwMS who switched from TERI to FUM. This retrospective analysis of the Komodo Health claims database included pwMS with ≥1 claim for TERI and MS diagnosis (ICD-10 code G35) between 1 Jan 2016 and 31 May 2022... ARRs decreased after switching from TERI to FUM, but was not statistically significant; however, patients had lower MS-related HRU and HCC after switching from TERI to FUM. Our results suggest FUM may be a reasonable and a cost-effective option for pwMS on prior TERI treatment.Study Supported by: Biogen"

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

Increased Prevalence of Fumarate-Induced Lymphopenia: A Single Center Retrospective Study (ACTRIMS Forum 2025) - "Background: Lymphopenia is an expected side effect of fumarate-based multiple sclerosis (MS) disease modifying therapies including dimethyl fumarate (DMF) and diroximel fumarate (DRF)... Lymphopenia incidence with DMF/DRF in a large real-world retrospective cohort is significantly higher at our center than previously reported. Our findings support previously identified associations between age and lymphopenia, and reveals new associations between lymphopenia and co-use of dalfampridine that require further study. These data could help inform safe DMT selection and surveillance."

Lymphopenia • Retrospective data • CNS Disorders • Hematological Malignancies • Infectious Disease • Multiple Sclerosis

Comparison of Serum Neurofilament Light Chain levels between Ocrelizumab vs Diroximel Fumarate in Multiple Sclerosis: A Retrospective Analysis (ACTRIMS Forum 2025) - "sNfL levels remained stable within normal range, and did not differ over more than 1 year between long-term OCR vs DRF in MS patients that were relapse-free and without any evidence of new MRI lesions. This suggests that it is highly unlikely for relapses to occur with normal sNfL levels. Limitations include small sample size, and lack of baseline neurofilament levels."

Retrospective data • CNS Disorders • Multiple Sclerosis • NEFL

TREAT-MS: Traditional Versus Early Aggressive Therapy for Multiple Sclerosis Trial (clinicaltrials.gov) - P=N/A | N=900 | Active, not recruiting | Sponsor: Johns Hopkins University | Recruiting ➔ Active, not recruiting | Trial completion date: Aug 2025 ➔ Aug 2026 | Trial primary completion date: Aug 2025 ➔ Aug 2026

Enrollment closed • Trial completion date • Trial primary completion date • CNS Disorders • Multiple Sclerosis

Adverse events analysis of Diroximel fumarate based on FAERS database. (PubMed, J Neurol Sci) - No abstract available

Adverse events • Journal

Real-world Treatment Outcomes in Black, Hispanic, Asian, and White People with Multiple Sclerosis Treated with Fumarates (P4-6.005). (PubMed, Neurology) - "Dimethyl fumarate (DMF) and diroximel fumarate (DRF) are disease-modifying therapies for relapsing MS...Dr. Shankar has stock in Biogen."

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

Diroximel fumarate acts through Nrf2 to attenuate methylglyoxal-induced nociception in mice and decrease ISR activation in DRG neurons. (PubMed, Diabetes) - "Co-treatment of MGO (1µM) with monomethyl fumarate (MMF) (10, 20, 50 µM), the active metabolite of DRF, prevented the ISR in both mouse and human DRG neurons. Our data show that targeting Nrf2 with DRF is a strategy to potentially alleviate pain associated with elevated MGO levels."

Journal • Preclinical • Diabetic Neuropathy • Immunology • Neuralgia • Pain • NFE2L2

Alkermes plc Reports Financial Results for the Fourth Quarter and Year Ended Dec. 31, 2024 and Provides Financial Expectations for 2025 (PRNewswire) - "Royalty revenues from XEPLION, INVEGA TRINZA/TREVICTA and INVEGA HAFYERA/BYANNLI for the fourth quarter were $36.5 million. VUMERITY manufacturing and royalty revenues for the fourth quarter were $35.0 million. FAMPYRA manufacturing and royalty revenues for the fourth quarter were $22.9 million. The company does not expect to record any FAMPYRA revenue going forward. RISPERDAL CONSTA manufacturing revenues for the fourth quarter were $14.7 million."

Commercial • Bipolar Disorder • CNS Disorders • Multiple Sclerosis • Schizophrenia

Severe gastrointestinal adverse reactions including perforation, ulceration, hemorrhage, and obstruction: A fumaric acid ester class new safety risk. (PubMed, Mult Scler) - "Review of postmarketing reports supported the identification of a class association between FAE drugs and serious GI ARs. As these reactions have implications for prescribing decisions and patient management, a safety labeling change was issued to add serious GI reactions to the Warnings and Precautions section of the prescribing information for FAE drugs."

Journal • CNS Disorders • Gastrointestinal Disorder • Hematological Disorders • Multiple Sclerosis

Descriptive Analysis of Patients Treated with Diroximel Fumarate and Dimethyl Fumarate-A Real-Life Experience. (PubMed, J Pers Med) - "Our real-life analysis of patients treated with DMF or DRF supports several studies' findings regarding decreased GI side effects with DRF vs. DMF without decreasing efficacy. However, our data show a greater reduction in lymphocytes in patients with DRF compared to DMF, so more studies are necessary."

Journal • CNS Disorders • Gastrointestinal Disorder • Infectious Disease • 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 | Not yet recruiting ➔ Recruiting

Enrollment open • Cardiovascular • Peripheral Arterial Disease

Real-World Experience with Diroximel Fumarate in Patients with Multiple Sclerosis: A Prospective Multicenter Study. (PubMed, Clin Drug Investig) - "This comprehensive analysis provides valuable insights into the real-world application of DRF, confirming its safety and tolerability while offering preliminary evidence of its efficacy in managing MS."

Clinical • Journal • Real-world • Real-world evidence • CNS Disorders • Gastrointestinal Disorder • Multiple Sclerosis

Safety, tolerability, and efficacy of diroximel fumarate in a cohort of Black patients with multiple sclerosis from the phase 3 EVOLVE-MS-1 study. (PubMed, Mult Scler Relat Disord) - P3 | "This study presents the first analysis of safety and efficacy of DRF in Black patients. Relapse rates remained low in Black patients on DRF, consistent with non-Black patients, and there were no new safety signals identified in the Black patient subgroup in EVOLVE-MS-1. Together, these outcomes support DRF as an effective treatment option in Black patients with RRMS."

Journal • P3 data • CNS Disorders • Gastrointestinal Disorder • Multiple Sclerosis

A Study to Evaluate Long-Term Safety of Vumerity and Tecfidera in Participants With Multiple Sclerosis (MS) (clinicaltrials.gov) - P=N/A | N=10500 | Active, not recruiting | Sponsor: Biogen | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • CNS Disorders • Multiple Sclerosis

Impact of Disease-modifying Therapies on Pregnancy Outcomes in Multiple Sclerosis: A cohort study from the German Multiple Sclerosis and Pregnancy Registry. (ECTRIMS 2024) - " In this prospective, observational cohort from the German MS and Pregnancy Registry, we analyzed pregnancy and fetal outcomes in women with/without DMT pregnancy exposure, stratified into different DMT exposure groups (interferon-β, glatiramer acetate, dimethyl/diroximel fumarate (Fumarates-group), sphingosin-1-phosphat-recptor-modulators (S1P-group), natalizumab (NTZ), anti-CD20-antibodies (CD20-group), others). Most pregnancy outcomes are unaffected by DMT pregnancy exposure, but our data underline the potential risk of reduced birth weights and/or a higher amount of SGA neonates in the S1P-group, late NTZ-subgroup, CD20-group, and the MS population in general."

CNS Disorders • Infectious Disease • Multiple Sclerosis • Small for Gestational Age • IFNB1

Observational comparison of flush symptoms between diroximel fumarate and dimethyl fumarate (ECTRIMS 2024) - "PwMS experience less flush symptoms under diroximel fumarate than they did under dimethyl fumarate overall as well as a reduction in symptom duration. The impact on daily life through flush as side effect of fumarate treatment also decreased, identifying diroximel fumarate as a reasonable alternative in patients suffering from flush symptoms under dimethyl fumarate."

Late-breaking abstract • CNS Disorders • Gastrointestinal Disorder • Multiple Sclerosis • Pain • Pruritus

Comparative Effectiveness and Risk of Severe Infection in Adult Patients with Multiple Sclerosis Treated with Diroximel Fumarate versus Anti-CD20 Monoclonal Antibodies: A Real-World Claims Analysis (ECTRIMS 2024) - "Baseline characteristics were used to match DRF pts 1:1 to anti-CD20s (ocrelizumab, ofatumumab) pts. This is the first study to report the risk of SIs and effectiveness for DRF vs anti-CD20s by age. Compared with anti-CD20s, there was a significantly lower risk of incident SIs in DRF-treated younger and older pts, and no significant difference in ARR. Study Support: Biogen"

Clinical • HEOR • Late-breaking abstract • Real-world • Real-world evidence • CNS Disorders • Infectious Disease • Multiple Sclerosis