A Randomised, Double-Blind Study Comparing the Gastrointestinal Tolerability of Tegomil Fumarate Versus Dimethyl Fumarate in Healthy Volunteers
Year: 2025
Type: article
Study designs: Randomized Controlled Trial, Clinical Trial
Abstract: Widely used to treat multiple sclerosis, dimethyl fumarate (DMF) is a prodrug metabolized in vivo to monomethyl fumarate (MMF) and methanol; the latter is a gastrointestinal (GI) irritant. GI adverse events (AEs) commonly cause DMF discontinuation. Tegomil fumarate (TMF) comprises two MMF moieties joined by tetraethylene glycol, a low molecular polyethylene glycol (PEG). TMF is cleaved in vivo to MMF and the pharmacologically inactive PEG. This randomised, double-blind study compared the GI tolerability of TMF 348 mg and DMF 240 mg, administered twice daily, in healthy adults (3:1 female:male ratio) aged 18–55 years. Participants completed daily questionnaires in an electronic diary, including the Modified Overall Gastrointestinal Symptom Scale (MOGISS), Modified Acute Gastrointestinal Symptom Scale, Flushing Symptom Questionnaire and an ad hoc quality of life assessment. The primary endpoint was the area under the curve (AUC) for each individual MOGISS symptom over 5 weeks of treatment. Between-group treatment differences for each MOGISS symptom AUC were analysed using hierarchical testing in a predefined sequence starting with abdominal pain. The study enrolled 210 participants; the full analysis set comprised 208 (155 females, 53 males). While AUC values were lower for TMF than DMF for most MOGISS symptoms, the between-group difference for abdominal pain was not statistically different (p = 0.0513) so all subsequent statistical analyses were considered exploratory. MOGISS total and composite score, the number of days with symptoms and number of symptoms were lower with TMF than DMF. Fewer participants receiving TMF (57.7%) versus DMF (73.6%) reported GI AEs or discontinued because of GI AEs (TMF n = 0, DMF n = 2). The between-group difference for the AUC of MOGISS abdominal pain score was not statistically different. However, compared with DMF, TMF showed improved GI tolerability profile in terms of self-assessed GI events and GI AEs leading to discontinuation. Dimethyl fumarate is a medication taken by mouth that is used to treat patients with multiple sclerosis, a disease in which the immune system (the body’s natural defences) causes inflammation and damages the nerves (myelin) in the brain and spinal cord. After taking a dose of dimethyl fumarate, substances in the medicine are quickly broken down into the active form, monomethyl fumarate, which helps to protect nerve cells from damage caused by inflammation and slows the progression of multiple sclerosis disease. However, dimethyl fumarate is also broken down into methanol, which irritates the gut. Patients often stop taking dimethyl fumarate because of gastrointestinal problems, such as vomiting, diarrhoea, bloating and constipation. Tegomil fumarate is a newer medicine used to treat multiple sclerosis. It is called a ‘hybrid medicine’, because it is similar to the ‘reference medicine’ dimethyl fumarate in that it is quickly broken down in the body into the same active form (monomethyl fumarate), but, unlike dimethyl fumarate, tegomil fumarate also breaks down into polyethylene glycol, which does not directly cause any physical reaction in the body. In this study, healthy adults were given dimethyl fumarate or tegomil fumarate, to compare the gastrointestinal side effects of these medications. Compared with dimethyl fumarate, the subjects reported that tegomil fumarate caused fewer gastrointestinal events, which were less intense, and it took a shorter time for the subjects to recover from these events. Studies are needed to confirm these results in patients with multiple sclerosis.
Source: Neurology and Therapy
Institutions: Hospital da Prelada, Neuraxpharm (Spain)
Language: English
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $7,400
Funder: Neuraxpharm
OpenAlex ID: W4416551024