Vidofludimus calcium lowers risk of progressive MS disability worsening
CALLIPER study is testing a daily dose against a placebo in 467 adults
Vidofludimus calcium, an experimental oral therapy from Immunic Therapeutics, reduced the risk of confirmed disability worsening and slowed brain shrinkage in people with progressive forms of multiple sclerosis (MS).
That’s according to top-line data from CALLIPER (NCT05054140), a Phase 2 clinical trial testing a daily dose of it against a placebo in 467 adults with progressive MS who hadn’t had a relapse in the two years before enrolling.
The therapy, which is also known as IMU-838, continued to be safe and well tolerated, and the benefits were seen even in patients without signs of active inflammation, supporting its potential for a population who often sees limited benefits from available therapies.
“We believe that vidofludimus calcium may represent a novel and exciting approach for people living with [progressive forms of MS], where there continues to be a huge unmet medical need,” Daniel Vitt, PhD, Immunic’s CEO, said in a company press release. “CALLIPER was designed to evaluate … vidofludimus calcium in a broad set of [progressive MS] patients to determine the suitability of advancing to a confirmatory phase 3 program. We look forward to discussing these results with healthcare authorities to determine appropriate next steps for vidofludimus calcium.”
In the meantime, Immunic remains on track in its testing of relapsing forms of MS in two Phase 3 clinical trials — ENSURE-1 (NCT05134441) and ENSURE-2 (NCT05201638) — which are expected to wrap up next year.
In MS, the immune system mistakenly launches inflammatory attacks on the protective covering around nerve fibers, or myelin sheath, causing progressive disability due to damage in the brain and spinal cord. These attacks are driven in part by overly active immune cells, such as B-cells and T-cells.
Vidofludimus calcium is a small molecule that’s designed to reduce the activity of those cells by blocking a protein called dihydroorotate dehydrogenase (DHODH). It’s also able to exert neuroprotective effects by activating a protein called Nurr1.
“The most significant unmet need in MS continues to be the lack of safe and effective therapies that can slow or halt disease progression,” said Andreas Muehler, MD, Immunic’s chief medical officer. “With this unique mode of action, vidofludimus calcium could become the first real neuroprotective treatment option for patients with progressive forms of MS.”
Results of CALLIPER study
The CALLIPER trial randomly assigned patients to receive either 45 mg of vidofludimus calcium or a placebo daily for up to 120 weeks. Among its 467 participants, 152 had primary progressive MS (PPMS) and 268 had nonactive secondary progressive MS (SPMS).
In the overall population, vidofludimus calcium reduced the risk of 24-week confirmed disability worsening, defined as an increase in Expanded Disability Status Scale (EDSS) scores sustained for at least 24 weeks, by 20% over a placebo. In patients with PPMS, who see symptoms worsen gradually over time from the disease’s onset, the risk of confirmed disability worsening was reduced by 30%. It was reduced by 15% in those with nonactive SPMS, which develops after a relapsing–remitting course.
“We are particularly thrilled to see such a clinically meaningful effect in the PPMS population, with a 30% reduction in the relative risk of 24-week confirmed disability worsening events, which would be the endpoint of a future Phase 3 registration study,” Vitt said.
On brain MRI scans, gadolinium-enhancing lesions, which represent areas of active inflammation, were observed in a small percentage of patients with nonactive SPMS (6.8%) or PPMS (17.8%). Most patients in the trial didn’t have lesions with active inflammation, which makes MS more difficult to treat.
Even among those without evidence of active inflammation, vidofludimus calcium reduced the risk of confirmed disability worsening by 29%. This supports the idea that it may have both anti-inflammatory and neuroprotective effects, a “breakthrough potential in addressing the high unmet need of slowing neurodegeneration in MS,” Muehler said.
MRI scans also showed vidofludimus calcium “substantially” slowed shrinkage in the thalamus, a key brain region for processing information, by 20%. Also, patients on vidofludimus calcium saw a reduction in the volume of new or enlarging lesions over time (by 0.22%), which increased by 2.97% for those on a placebo.
Muehler called these results “exciting” and said they “further validate vidofludimus calcium’s scientific rationale, specifically driven by the impressive numerical benefit in reducing disability worsening, which deserves to be further tested in a Phase 3 registration trial.”
“The CALLIPER results also corroborate the benefit on disability progression expected for people suffering from relapsing forms of MS, allowing for a beneficial read-through to our ongoing phase 3 ENSURE trials,” Muehler said.
Vidofludimus calcium was generally safe and well tolerated, with serious side effects and side effects related to treatment occurring at similar rates as the placebo. No new safety concerns were reported.
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