What Is Diroximel Fumarate?
Diroximel Fumarate is an FDA-approved medication for Multiple Sclerosis. This oral capsule is an immunomodulating drug that works by crossing the blood-brain barrier and increasing brain glutathione levels. This mechanism may help to reduce inflammation and protect nerve cells in the brain. While primarily used for Multiple Sclerosis, Diroximel Fumarate is also being investigated in clinical trials for other conditions such as Schizophrenia Disorders and for its impact on medication adherence. The first trial for Diroximel Fumarate began on 2020-12-19, with the latest trial projected to conclude on 2026-03-19. Across 11 total trials, it has involved 13,477 participants.
Uses and Conditions Under Study
Diroximel Fumarate is primarily studied for its role in treating Multiple Sclerosis (MS), a chronic disease affecting the brain and spinal cord. As an immunomodulating drug, it aims to manage MS symptoms by reducing inflammation and protecting nerve cells. A significant number of trials, totaling 9 trials, focus on various forms of MS, including:
- Multiple Sclerosis (4 trials)
- Relapsing Forms of MS (2 trials)
- Relapsing Forms of Multiple Sclerosis (2 trials)
- Relapsing Remitting Multiple Sclerosis (1 trial)
Beyond MS, Diroximel Fumarate is also being investigated for other distinct conditions. One trial explores its potential role in improving Medication Adherence, which is crucial for effective long-term treatment across various health conditions. Another trial is examining its use in Schizophrenia Disorders, exploring new therapeutic avenues for these complex mental health conditions. Additionally, one trial involves Healthy Volunteers to assess the drug's safety and how it is processed by the body in individuals without the target disease.
Dosing
Diroximel Fumarate is available as an oral capsule. In clinical trials, it has been studied under various treatment arms and formulations. These include specific cohorts such as TP Cohort A and TP Cohort B, which further divided into sub-cohorts investigating Diroximel Fumarate (DRF) alongside other medications like Fingolimod. The drug has also been studied in open-label extension periods for participants from these cohorts. Specific formulations or brand names mentioned in studies include Diroximel Fumarate (DRF), Bafiertam, and Vumerity. Studies have also differentiated between participant populations, such as DRF for Chinese Participants and DRF for Caucasian Participants. The drug is administered as specified in the treatment arm of each study, often in a double-blind manner for initial phases, followed by open-label extensions.
Side Effects
In a study (NCT05083923) evaluating Diroximel Fumarate in adult participants from the Asia-Pacific region with relapsing forms of multiple sclerosis, specific side effect rates compared to placebo were not available. The study focused on pharmacokinetic and safety profiles. The following percentages represent the number of participants who experienced certain categories of safety events during the study duration (Parts 1 and 2 combined):
- Among 52 Japanese participants, the most frequently observed safety events included potentially clinically significant abnormalities in laboratory parameters (53.8%), clinically relevant abnormalities in vital sign parameters (26.9%), and abnormal shifts in 12-lead electrocardiogram (ECG) values (13.5%). Treatment-emergent serious adverse events (TESAEs) occurred in 11.5% of Japanese participants. No Columbia Suicide Severity Rating Scale (C-SSRS) events were reported in this cohort.
- Among 47 Chinese participants, potentially clinically significant abnormalities in laboratory parameters were observed in 34.0% of participants. Clinically relevant abnormalities in vital sign parameters occurred in 14.9%, and abnormal shifts in 12-lead ECG values were seen in 10.6%. Treatment-emergent serious adverse events (TESAEs) affected 12.8% of Chinese participants, and Columbia Suicide Severity Rating Scale (C-SSRS) events were reported in 4.3% of participants.
Clinical Trial Results
The clinical study NCT05083923 investigated Diroximel Fumarate in adult participants from the Asia-Pacific region with relapsing forms of multiple sclerosis. This study primarily evaluated the drug's pharmacokinetic (PK) profile and safety, rather than efficacy endpoints like relapse rates or disease progression.
Pharmacokinetic Profile
Diroximel Fumarate is converted in the body into its active metabolite, monomethyl fumarate (MMF), and another metabolite, 2-hydroxyethyl succinimide (HES). The pharmacokinetic analysis focused on how these substances are absorbed, distributed, metabolized, and eliminated.
- For MMF in Japanese participants:
- The average total exposure (Area Under the Concentration-Time Curve from time zero to time of last measurable concentration, AUClast) was 3.6 hour*microgram per milliliter (h*ug/mL).
- The average maximum concentration (Cmax) reached in the blood was 1.2 ug/mL.
- The median time it took to reach this maximum concentration (Tmax) was 3.8 hours.
- The median elimination half-life (t½), which is the time it takes for the amount of MMF in the body to be reduced by half, was 1.3 hours.
- For HES in Japanese participants:
- The average total exposure (AUClast) was 75.3 h*ug/mL.
- The average maximum concentration (Cmax) was 11.6 ug/mL.
- The median time to reach maximum concentration (Tmax) was 5.80 hours.
Plasma concentrations of MMF and HES were also measured at various time points, showing consistent levels throughout the study in both Japanese and Chinese cohorts.
Currently Recruiting Trials
Diroximel Fumarate is currently being investigated in several clinical trials across different health conditions. These studies aim to gather more information about the drug's effects, safety, and how it impacts patients' lives.
One study, NCT06957808, sponsored by King's College London, is exploring the effect of Diroximel Fumarate on glutathione levels in individuals with schizophrenia disorders. Schizophrenia is a severe psychiatric illness affecting about 1% of people worldwide. This study aims to enroll 30 participants to understand potential new therapeutic avenues.
Biogen is sponsoring two pregnancy exposure registries for Vumerity (Diroximel Fumarate) in women with Multiple Sclerosis (MS). The study NCT05658497 aims to estimate the risk of major congenital malformations in infants born to women exposed to the drug during pregnancy, with an enrollment target of 908 participants. Similarly, NCT05688436 seeks to learn more about the safety of Diroximel Fumarate when taken during pregnancy and the health of babies, targeting 1178 participants. Both are observational studies, not assigned a traditional phase.
Another observational study, NCT04676204, sponsored by Monash University, is investigating the relationship between the burden of oral disease-modifying therapies and medication adherence in Multiple Sclerosis. This study includes Diroximel Fumarate among other therapies and plans to enroll 323 participants over approximately 4.5 years.
Where to Participate
Clinical trials for Diroximel Fumarate are currently open at several locations across the United States. Currently, there are 3 active sites in 3 different states where you might be able to participate:
- Aurora, Colorado
- Eden Prairie, Minnesota
- Durham, North Carolina
These studies generally seek participants aged between 18 and 99 years, of all genders. It is important to note that these trials are not recruiting healthy volunteers, but rather individuals with specific medical conditions. Some studies may also include children, depending on the specific research.
Development Timeline
The journey of Diroximel Fumarate through clinical development began in late 2020, with the first trial initiated on December 19, 2020. Since then, a total of 11 clinical trials have been launched, aiming to enroll over 13,477 participants.
Biogen has been the primary driver of this research, sponsoring 8 of these studies, with contributions from Banner Life Sciences LLC, King's College London, and Monash University. Early research initially focused on conditions such as Irritable Bowel Syndrome with Constipation (IBS-C) and hyperphosphatemia.
Over time, the development pipeline expanded significantly to include various forms of Multiple Sclerosis, including Relapsing Forms of Multiple Sclerosis and Relapsing Remitting Multiple Sclerosis. More recently, investigations have broadened to include medication adherence in MS and even Schizophrenia Disorders, demonstrating a diverse therapeutic exploration. The trials have progressed through Phase 1 and Phase 3 studies, alongside several observational and non-specified phase investigations, with the latest trial projected to conclude in March 2026.