US patent likely for vidofludimus calcium at relapsing MS trial dose

Immunic Therapeutics has been notified of the intent to grant a U.S. patent covering the use vidofludimus calcium (IMU-838) in treating relapsing forms of multiple sclerosis (MS) at a daily dose of about 10 to 45 mg.

That range covers the two IMU-838 doses shown to be effective in relapsing MS patients in earlier clinical trials, and the 30 mg dose currently being investigated in the Phase 3 ENSURE-1 (NCT05134441) and ENSURE-2 (NCT05201638) studies.

U.S. patent number 17/391,442, titled “Treatment of Multiple Sclerosis Comprising DHODH Inhibitors,” also covers the use of other salt, as well as free acid, forms of vidofludimus calcium in relapsing MS. It is expected to be valid into 2041, with extensions possible.

“Allowance of this patent … including the 30 mg dosage used in our ongoing twin phase 3 ENSURE trials, significantly bolsters the multilayered proprietary intellectual property position we have strategically built around our lead, late-stage program for patients with multiple sclerosis,” Daniel Vitt, PhD, Immunic’s president and CEO, said in a company press release.

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Vidofludimus calcium is designed to lower the inflammation driving MS

MS is marked by the immune system mistakenly launching an inflammatory attack against myelin, a protective sheath that wraps around and protects nerve cell fibers. This attack is driven by many types of immune cells, including T-cells and B-cells.

Vidofludimus calcium is an oral small molecule designed to reduce the inflammation that drives MS by blocking dihydroorotate dehydrogenase (DHODH), an enzyme essential for activated T-cells and B-cells to grow in number and survive. It also exerts neuroprotective effects by activating a nerve protein called Nurr1.

A six-month Phase 2 clinical trial, called EMPhASIS (NCT03846219), investigated the experimental therapy in 268 people with relapsing-remitting multiple sclerosis (RRMS).

Data supported the safety and efficacy of vidofludimus calcium at 35 mg and 40 mg once daily doses, with a significant reduction in the total number of brain lesions — by more than 70% compared with a placebo — and the proportion of treated patients with disability progression cut by more than half relative to those on a placebo (1.6% vs. 3.7%).

RRMS patients at six months of treatment also showed signs of reduced nerve damage, as determined by a 19% decrease in neurofilament light chain (NfL), an established marker of nerve cell damage, versus a 7% increase in levels among the placebo group.

Vidofludimus calcium under evaluation in relapsing and progressive MS trials

The ENSURE trials aim to confirm the safety and efficacy of vidofludimus calcium observed in EMPhASIS.

These global, Phase 3 trials collectively are enrolling more than 2,000 adults with either RRMS or active secondary progressive MS, who will be randomly assigned to a once daily 30 mg dose of the oral treatment or a placebo tablet for nearly 1.5 years (72 weeks).

With interim data expected in late 2024, the trials’ primary goal is to determine the time to a first relapse. Secondary measures include changes in brain lesion volume, time to disability progression, cognitive changes, and brain volume changes.

Immunic also is running the global, Phase 2 CALLIPER study (NCT05054140) evaluating IMU-838 against a placebo for about 2.5 years (120 weeks) in up to 467 people with either primary progressive MS (PPMS) or active or nonactive SPMS.

An interim analysis covering about half of these progressive MS patients, treated daily with a 45 mg tablet for about a year (48 weeks), also showed reductions in NfL levels and smaller increases in another biomarker of damage to nerve-supporting cells relative to a placebo. These findings appear to support the therapy’s neuroprotective effects across all forms of MS.

Other patents, issued in the U.S., Europe and elsewhere, cover various aspects of vidofludimus calcium, such composition-of-matter for its salt forms, including the specific form used in clinical trials.

Patent applications also are pending for a polymorph of the molecule (a chemical that has the same composition as vidofludimus calcium but takes on a different shape), production methods, dosing regimens, and broader applications in neurodegenerative diseases. If granted, these could extend protection until at least 2044.

Undisclosed patents also are being pursued to enhance exclusivity, the company announced.

“We remain committed to protecting the technology around this phase 3 asset, in order to assure extended exclusivity upon potential regulatory approval from the U.S. Food and Drug Administration,” Vitt said.