Vidofludimus Calcium (IMU838) is a new, selective inhibitor of the enzyme dihydroorotate dehydrogenase (DHODH) from the biotech company Immunic Therapeutics. The manufacturer is currently testing it in patients with relapsing-remitting multiple sclerosis in a phase 2 study.
The inhibition of the enzyme DHODH, which is involved in DNA and RNA synthesis, leads to the proliferation inhibition of T and B cells and can therefore be used for the treatment of autoimmune diseases. In relapsing MS, this mechanism of action has been used for several years – the drug Aubagio® (active ingredient: teriflunomide) also relies on the inhibition of DHODH.
Differences between Vidofludimus and Teriflunomide
Vidofludimus Calcium has a different chemical structure compared to Teriflunomide, the enzyme inhibition is about 2.6 times more effective compared to Teriflunomide, especially with regard to the inhibition of T-lymphocyte proliferation and the secretion of IL-17 and IFN-γ, two important inflammation-promoting cytokines. The serum half-life of about 30 hours provides the basis for the once-daily administration of Vidofludimus Calcium, with rapid dosing up to steady-state levels within 5 days and the ability to wash out the drug quickly if needed. This is another difference to Terflunomide, which remains in the body for a very long time due to its enterohepatic recycling and requires a special washout procedure.
The safety and efficacy of Vidofludimus Calcium were investigated in a double-blind, 24-week, placebo-controlled phase 2 study in patients with relapsing-remitting multiple sclerosis aged 18 to 55 years. The results of the so-called EMPhASIS study were published last year (Fox et al. Ann Clin Transl Neurol 2022 Jul;9(7):977-987).
Effect and Side Effects of Vidofludimus
The patients in this phase 2 study were treated daily with either 30 mg Vidofludimus Calcium (IMU838), 45 mg Vidofludimus Calcium or placebo. The primary endpoint of the study was the cumulative number of new, active MRI lesions after 24 weeks of observation. Here, in the placebo group, there were 6.4 active lesions after 24 weeks, while in the treatment group with 45 mg Vidofludimus Calcium there were only 2.4 active lesions, which represents a statistically significant difference between the two groups. Significant differences between the two dosages of Vidofludimus Calcium were not found, nor were there any in terms of adverse events. Overall, no increased incidence of infectious, hepatic or renal treatment-related adverse events was found. Serious adverse events occurred in 1% of the patients treated with placebo and 1% of those treated with Verum.
In summary, the phase II study shows that treatment with Vidofludimus-Calcium in patients with relapsing-remitting multiple sclerosis leads to a significant reduction in new lesions in magnetic resonance imaging and overall has a favorable safety profile. These results justify testing the substance now in a larger and registration-relevant phase III program. This program is called ENSURE and consists of twin studies to evaluate the efficacy, safety and tolerability of Vidofludimus Calcium in relapsing MS compared to placebo. Data from an interim analysis are expected by the end of 2024, and the results of the first ENSURE study are expected by the end of 2025. We look forward to the results.
Study with Vidofludimus in Progressive MS
In addition to the study program for relapsing MS, the manufacturer is currently also conducting a multicenter, randomized, double-blind, placebo-controlled phase 2 study in progressive MS to investigate the neuroprotective potential of Vidofludimus Calcium. In the study named CALLIPER, about 450 patients in North America, Western, Central and Eastern Europe will be treated either with Vidofludimus-Calcium or placebo. The primary endpoint of the study is the percentage change in brain volume over a period of up to 120 weeks. Data from the interim analysis of the CALLIPER study is expected in the second half of 2023, with the final data expected by the end of 2024.
