Treatment Persistence, Safety, Tolerability, and Effectiveness of Diroximel Fumarate in the Real-World: Design of the Phase 4 Experience–US Study

Background: Diroximel fumarate (DRF) is an oral fumarate approved in the United States (US) for relapsing multiple sclerosis (MS). DRF demonstrated favorable gastrointestinal (GI) tolerability in Phase 3 clinical studies. In a randomized, 5-week trial vs dimethyl fumarate (DMF), DRF showed lower rates of GI adverse events (AEs; DRF 35% vs DMF 49%) and discontinuation due to GI AEs (DRF 0.8% vs DMF 4.8%). DRF also demonstrated a low (0.7%) rate of discontinuation due to GI AE, a high (93%) rate of treatment adherence, and reduced relapse rates and radiological disease activity compared to baseline in an open-label, 2-year study. However, a lack of data is available in patients treated with DRF outside the clinical trial setting. Objectives: The EXPERIENCE–US study is a Phase 4, prospective, observational study to assess treatment persistence, clinical effectiveness, safety, and tolerability of DRF in routine clinical practice. Methods: Patients aged ?18 years with a confirmed diagnosis of MS who are newly prescribed DRF in routine clinical practice per the US Prescribing Information are eligible to participate. Once enrolled, patients will be followed for a treatment period of 24 (±2) months with study visits per standard of care approximately every 6 months. Primary objective is to characterize persistence to therapy (primary endpoint: proportion of patients on DRF treatment at Year 1). Secondary objectives will assess short-term (3 months) and long-term (Year 2) persistence, effect of DRF on relapses, impact of DRF on cognition (change in Processing Speed Test score), impact of DRF on patient-reported outcomes (change in Neuro-QoL domain score, Patient Determined Disease Steps, and Work Productivity and Activity Impairment Due to MS), and real-world safety and tolerability. The study will also assess the impact of DRF on serum neurofilament light chain levels and dynamics of post-DRF absolute lymphocyte count (ALC) reconstitution. Patients who discontinue DRF with an ALC of <0.91×109/L may enter an optional post-DRF ALC follow-up period for up to 6 months or until ALC reaches ?0.91×109/L or another disease-modifying therapy is started. Results: The EXPERIENCE–US study plans to enroll approximately 200 patients across several sites in the US. We expect the first patient to be enrolled in early 2021. Conclusions: The DRF EXPERIENCE–US Phase 4 study will characterize treatment persistence, safety, and clinical effectiveness of DRF in routine clinical practice. Study Support: Biogen

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