Vidofludimus calcium, also known as IMU-838, is an experimental oral therapy with anti-inflammatory and neuroprotective properties. It is being investigated for relapsing and progressive forms of multiple sclerosis (MS).
Immunic Therapeutics is developing the therapy, which also is being tested for other inflammatory or autoimmune conditions.
MS is caused by an inflammatory attack that the immune system erroneously launches against myelin, a protective covering around nerve cells that is important for their function and survival. This inflammation is driven by a number of immune cell types, including B-cells and T-cells.
Vidofludimus calcium is a small molecule that interferes with the normal metabolism of these immune cells, reducing the production of pro-inflammatory molecules and eventually leading to cell death. It works by inhibiting dihydroorotate dehydrogenase (DHODH), an enzyme that is essential for the proliferation of activated T-cells and B-cells.
According to Immunic, this treatment is different from other approved MS therapies in that it is expected to dampen the function of activated immune cells while leaving nonactivated and slowly dividing cells largely unaffected. This will allow the immune system to continue to fight infections.
Aubagio (teriflunomide) is an approved oral MS therapy that also works to inhibit the DHODH enzyme. However, it has been associated with a number of side effects, mostly due to its ability to interact with other enzymes. Vidofludimus calcium is a second-generation inhibitor designed to bind more selectively to its target, which could potentially result in fewer off-target effects.
Vidofludimus calcium is available in an oral tablet formulation. In clinical trials, the therapy is being tested at both 30 mg and 45 mg doses. The 30 mg daily dose is being evaluated in people with relapsing forms of MS, while 45 mg per day is being tested in patients with progressive forms of the disease.
In Phase 1 trials involving healthy volunteers, vidofludimus calcium was deemed generally safe and well-tolerated at daily doses of up to 50 mg. These results prompted Immunic to begin testing the therapy in MS clinical trials.
The EMPhASIS Phase 2 trial (NCT03846219) investigated vidofludimus calcium in 268 adults with relapsing-remitting MS (RRMS) and active disease. Participants were randomly assigned to take one of three doses of the medication — 10 mg, 30 mg, or 45 mg — or a placebo, once daily for 24 weeks, or about six months.
Top-line results from EMPhASIS showed that both the 30 mg and 45 mg doses significantly reduced total active lesions — which included new and enlarging ones, as well as lesions showing evidence of ongoing inflammation. Compared with a placebo, the 30 mg dose reduced those lesions by 76%, while patients on the 45 mg dose had 71% fewer lesions.
Other measures of efficacy, such as the number of inflammatory lesions and changes in Expanded Disability Status Scale (EDSS) scores, also tended to benefit from the use of vidofludimus calcium. Also, only 1.6% of patients had experienced 24-week confirmed disability progression after six months of treatment, compared with 3.7% of those given a placebo.
Both doses were generally safe and well-tolerated. There were no signs of liver damage, which is a serious side effect of Aubagio treatment. In addition, the rates of treatment discontinuation were lower than with a placebo.
After completing the main trial, most patients chose to join an open-label extension period, in which all are receiving vidofludimus calcium for up to 9.5 years. Such open-label extensions aim to evaluate the longer-term effects of a medication that already has been tested in a clinical trial.
After two years in the extension, a large proportion of patients (94.5%) still had not experienced sustained disability accumulation, which compares favorably to rates of progression seen with approved MS treatments. Also, only 6.2% of patients experienced a relapse in that period.
Immunic is running two identically designed Phase 3 trials — ENSURE-1 (NCT05134441) and ENSURE-2 (NCT05201638) — to continue evaluating vidofludimus calcium in relapsing forms of MS. The trials will involve patients with RRMS and active secondary progressive MS.
Both are enrolling at sites worldwide and aim to include 1,050 patients each. Immunic has created a website to help potential participants connect with these trials.
Participants will be randomly assigned to receive a 30 mg dose of vidofludimus calcium or a placebo once daily for 72 weeks (almost 1.5 years). Neither participants nor researchers will know which patients are receiving the medication and which the placebo.
The primary goal is to determine the time to first relapse among these individuals. Key secondary measures include brain lesion volume, time to disability progression, cognitive changes, and brain volume changes.
After completing the randomized period in the ENSURE trials, patients may be eligible to participate in an open-label extension, in which all participants will receive the 30 mg dose of the active treatment for up to eight years.
ENSURE-1 enrolled its first participant in November 2021, and ENSURE-2 recruited its first patient in January 2022. Interim data are expected in late 2024, and a full data readout may be available toward the end of 2025.
The CALLIPER Phase 2 trial (NCT05054140) also is investigating the neuroprotective effects of vidofludimus calcium in people with progressive forms of MS. Eligible participants will have primary progressive MS or SPMS with no evidence of relapses in the past two years.
A total of 450 participants are being recruited at sites across the U.S., Canada, and Europe. Each will be assigned at random to either vidofludimus at a daily dose of 45 mg or a placebo. Treatment will continue for 120 weeks, with an optional open-label extension period of up to eight years that will evaluate the therapy’s long-term effects.
CALLIPER’s main goals are to assess changes in the rate of brain volume loss and the proportion of patients with confirmed disability progression, defined as an increase in Expanded Disability Status Scale (EDSS) scores for at least 24 weeks.
The first patient was enrolled in CALLIPER in September 2021, and the trial is expected to end in 2024.
Vidofludimus calcium was generally safe and well-tolerated in MS clinical trials. The most frequently reported side effects were:
These side effects were generally mild in nature and were not more common in patients receiving the active medication than in those on a placebo.
Multiple Sclerosis News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis, or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website.
Vidofludimus calcium is an experimental therapy that is still in clinical trials for multiple sclerosis (MS). It is expected to lower inflammation and prevent MS damage by inhibiting the growth of certain activated immune cells. In clinical trials, vidofludimus calcium treatment resulted in a significant reduction in the number of lesions in people with relapsing-remitting multiple sclerosis. The therapy also showed some promising benefits in relapse rates and disability worsening among these patients.
Phase 3 clinical trials testing vidofludimus calcium for the treatment of relapsing types of multiple sclerosis are underway, as are Phase 2 trials for progressive forms of the disease. According to Immunic Therapeutics, the therapy’s developer, these Phase 3 trials may support regulatory applications seeking approval for the medication from the U.S. Food and Drug Administration (FDA). It is too soon, however, to determine if or when the medication could be approved by the FDA.
Clinical trials of vidofludimus calcium have not, and are not, enrolling multiple sclerosis patients who are pregnant or breastfeeding. Whether the therapy can be safely used in these situations is not known.
Some patients in clinical trials have seen benefits following six months of treatment with vidofludimus calcium. In the EMPhASIS Phase 2 trial, which investigated the therapy against a placebo in patients with relapsing-remitting multiple sclerosis, treatment significantly lowered the number of active brain lesions after about six months. But given that multiple sclerosis can manifest differently in every patient, individual responses to treatment also may vary.
While weight gain was not reported as a side effect of vidofludimus calcium in multiple sclerosis clinical trials, hair loss was experienced by some patients. It is recommended that patients talk with their healthcare providers if any unexpected side effects arise when using a new therapy.
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