Therapeutic: vidofludimus for relapsing–remitting multiple sclerosis

Multiple sclerosis is a progressive autoimmune disease that affects the brain, spinal cord and optic nerve. The myelin coating that protects the nerves is attacked and damaged by the body’s own immune system

By far the most common form of the disease is relapsing–remitting multiple sclerosis (RRMS), although some patients are likely to develop more progressive forms in time.

Patients with RRMS experience clearly defined attacks of new or increasing neurologic symptoms followed by periods of remission when all of the symptoms may temporarily disappear … or some may continue and become permanent.

There is no cure. And, although some patients gain improvements from drug treatment, more effective alternatives are greatly needed. One potential new treatment, vidofludimus, is being developed by Immunic Therapeutics.1

It is an orally available selective immune modulator that inhibits the intracellular metabolism of activated immune cells by blocking the enzyme dihydro-orotate dehydrogenase (DHODH).

It acts on activated T and B cells; but, as it largely has no effect on other immune cells, the body should still be able to fight off infections. It may also have an antiviral effect against some viruses.

Preclinical studies showed it inhibited DHO oxidation by DHODH.1 In an open label, partial parallel group Phase I study, 12 healthy subjects were given single doses of the drug, either 10 mg (fed state) or 10–40 mg (fasted).2

In a multiple ascending dose study, a further 52 subjects were given multiple 30–50 mg doses in a double-blind, placebo-controlled, parallel group study. Food had no effect on the pharmacokinetics and steady state concentrations were achieved within 6–8 days for the 30–50 mg groups. Its mean plasma half-life at steady state was about 30 hours, making it appropriate for once daily dosing.

A multicentre, double-blind, placebo-controlled, randomised Phase II trial was done in 210 patients with RRMS who were given 30 or 45 mg of the drug or a placebo.3

It met all of its primary and key secondary endpoints, notably a 62% reduction compared with the placebo in the cumulative number of combined unique active MRI lesions up to week 24 in those subjects given 45 mg daily doses of the drug, and a 70% reduction in those given 30 mg once a day.

Lesion suppression was already evident after 6 weeks. There were also positive trends in other secondary endpoints, including relapse activity and neurological status. It was well tolerated. Phase III trials are now planned using a 30 mg once daily dose.

References

  1. A. Muehler, et al., J. Multiple Scler. Rel. Disord. 43, 102129 (2020).
  2. A. Muehler, et al., Eur. J. Drug. Metab. Pharmacokinet. 45, 557 (2020).
  3. R.J. Fox, MSVirtual 2020/Joint ACTRIMS–ECTRIMS Meeting (11–13 September 2020), Abstr. 1409.

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