Phase 3 trials of vidofludimus calcium in relapsing MS enrolled
Ability of experimental therapy to delay time to first relapse to be measured
Enrollment is now complete in the twin Phase 3 clinical trials testing Immunic Therapeutics‘ oral small molecule vidofludimus calcium in adults with relapsing forms of multiple sclerosis (MS).
ENSURE-1 (NCT05134441) has enrolled 1,121 patients and ENSURE-2 (NCT05201638) has enrolled 1,100 patients at more than 100 locations in 15 countries, including the U.S. Top-line data is expected by the end of next year.
“The on-schedule enrollment of the final patients in our phase 3 ENSURE trials of vidofludimus calcium marks another significant milestone for our late-stage MS program, bringing us meaningfully closer to a potential new treatment option for people living with RMS [relapsing multiple sclerosis],” Daniel Vitt, PhD, CEO of Immunic, said in a company press release. “We eagerly anticipate the top-line data from both ENSURE trials by the end of 2026.”
In the meantime, additional data from CALLIPER (NCT05054140), a Phase 2 clinical trial testing vidofludimus calcium against a placebo in 467 adults with progressive forms of MS, has shown even greater reductions in the risk of 24-week confirmed disability worsening (CDW) than previously reported.
“Our recently released positive phase 2 CALLIPER trial data in [progressive MS] underlined vidofludimus calcium’s neuroprotective potential and its ability to slow disease progression in MS patients,” said Vitt. “We are very excited that additional analyses of time to 24-week confirmed disability worsening further support this potential, highlighting a significant opportunity ahead.”
Vidofludimus calcium designed to block enzyme, protect nerve fibers
In MS, the immune system mistakenly launches inflammatory attacks on the myelin sheath — a protective covering around nerve fibers — causing progressive damage to the brain and spinal cord. These attacks are in part driven by overactive immune cells such as B-cells and T-cells.
Vidofludimus calcium is designed to block dihydroorotate dehydrogenase, an enzyme needed for the growth of T-cells and B-cells. It also protects nerve fibers by activating Nurr1. This dual mechanism is expected to reduce inflammation and protect against damage, thereby slowing progression of the disease.
The experimental therapy is being tested in relapsing forms of MS in the ENSURE clinical program. More than 2,200 adults with evidence of disease activity in the past 1 to 2 years were randomly assigned to receive a daily 30 mg dose of oral vidofludimus calcium, or a placebo, for nearly 1.4 years.
Participants will then be given the option to join an open-label extension, in which all will receive vidofludimus calcium for up to eight years.
In both clinical trials, the main goal is to determine whether vidofludimus calcium can delay the time to a first relapse compared with a placebo. Secondary measures include time to 12-week CDW progression, defined as an increase in Expanded Disability Status Scale scores sustained for at least 12 weeks. Other measures include volume of new lesions, time to sustained clinically relevant changes in cognition, and brain atrophy (shrinkage).
“We are extremely proud to have reached this key milestone for our ENSURE program of vidofludimus calcium, right on schedule,” said Werner Gladdines, Immunic’s chief development officer, adding that “successfully completing enrollment … represents a major achievement and a true team effort.”
Latest data suggest therapy has neuroprotective potential
The CALLIPER trial randomly assigned patients to receive either vidofludimus calcium, at a daily dose of 45 mg, or a placebo, for up to 120 weeks (more than two years). Among its participants, 152 had primary progressive MS (PPMS), 268 had nonactive secondary progressive MS (SPMS), and 47 had active SPMS.
Top-line data announced earlier this year showed vidofludimus calcium significantly reduced the risk of 24-week CDW. The company has now shared additional data showing even greater benefits across populations and suggesting vidofludimus calcium has the potential to be neuroprotective.
In the overall trial population, the experimental therapy reduced the risk of 24-week CDW by 24%. Benefits were higher for those with PPMS (a 33% reduction) and active SPMS (a 34% reduction), while people with nonactive SPMS experienced a 19% reduction in disability worsening.
If approved, we believe vidofludimus calcium, with its attractive safety and tolerability profile … could potentially transform the oral MS therapy market, offering a unique first-in-class treatment option by addressing the full spectrum of this disease.
Reductions in the risk of 24-week CDW were observed even in patients without signs of active inflammation in MRI scans, a group that has largely not benefited from available treatments for MS. Vidofludimus calcium reduced the risk of CDW in patients without gadolinium-enhancing lesions — which represent areas of active inflammation — by 34% compared with a placebo.
This “supports clinically measurable neuroprotective effects of vidofludimus calcium, consistent with its Nurr1 activation mechanism,” Vitt said.
“If approved, we believe vidofludimus calcium, with its attractive safety and tolerability profile … could potentially transform the oral MS therapy market, offering a unique first-in-class treatment option by addressing the full spectrum of this disease,” he added.
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