Immunic Completes Patient Enrollment for Phase 2 CALLIPER Study of Progressive MS

Daniel Vitt, PhD

According to an announcement, enrollment for the phase 2 CALLIPER trial (NCT05054140) assessing Immunic’s investigational agent IMU-838 in individuals with progressive multiple sclerosis (PMS) has concluded. An interim analysis using biomarker data in half of the cohort will be readout later this year, with topline data for the entire cohort expected in April 2025.¹

The trial is comprised of 467 patients with primary PMS, or active or non-active secondary PMS, who were randomly assigned to either 45 mg daily doses of IMU-838, or vidofludimus calcium, or placebo, for a 120-week period. This international, multicenter, double-blind trial will use annualized rate of percent brain volume change as the primary end point, with secondary end points that include annualized rate of change in whole brain atrophy and time to 24-week confirmed disability progression using the Expanded Disability Status Scale (EDSS).

"Our phase 2 CALLIPER trial is designed to corroborate the neuroprotective potential of vidofludimus calcium in a progressive patient population. Enrollment of the final PMS patient, according to plan, is another important milestone in the clinical development of our lead asset in MS,” Daniel Vitt, PhD, chief executive officer and president at Immunic, said in a statement.¹

IMU-838, a known inhibitor of the enzyme dihydroorotate dehydrogenase (DHODH), which is a key enzyme in the metabolism of overactive immune cells and virus-infected cells, has shown promising results in treating patients with relapsing forms of MS thus far. The agent has also shown an ability to selectively act on hyperactive T and B cells while leaving other immune cells largely unaffected an enabling normal immune system function to occur.

Vitt added, "We believe that the data from the CALLIPER trial, along with that from our ENSURE program, in conjunction with vidofludimus calcium's postulated neuroprotective effects as a first-in-class nuclear receptor related 1 (Nurr1) activator as well as its strong safety and tolerability profile shown, to date, may further strengthen the uniqueness of this treatment approach compared to other oral MS medications and result in a highly attractive commercial positioning."¹

CALLIPER runs concurrent with the phase 3 ENSURE programs, which are comprised of 2 identical, double-blind, twin phase 3 trials, titled ENSURE-1 and ENSURE-2. These studies, which include approximately 1050 adult patients with active relapsing-remitting MS, are designed to evaluate the efficacy, safety, and tolerability of IMU-838 in a 30-mg daily dose vs placebo. Patients are mainly assessed on time to first relapse, but also volume of new T2 lesions, time to confirmed disability progression, time to sustained clinically relevant changes in cognition, and percentage of whole brain volume change, grey matter volume, and white matter volume.²

READ MORE: Argenx Reports Positive Findings in ADHERE Study of Chronic Inflammatory Demyelinating Polyneuropathy

The company decided to move IMU-838 to a phase 3 setting after it previously showed robust results in the phase 2 EMPhASIS trial (NCT03846219). In June 2023, data from the open-label extension (OLE) of EMPhASIS showed that the agent was safe and tolerable in patients with relapsing-remitting MS for up to 4 years. In total, 254 individuals with the disease completed the 24-week, double-blind treatment period, and 209 remained on OLE treatment where they received either 30 or 45 mg of the therapy once daily.³

Presented at the 2023 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held May 31 to June 3, in Aurora, Colorado, 193 patients received at least 96 weeks of treatment and 144 were treated for at least 144 weeks. Led by Robert J. Fox, MD, neurologist, Mellen Center for Multiple Sclerosis, and Vice-Chair for Research, Neurological Institute, Cleveland Clinic, there was a low discontinuation rate, with 5.3% of patients dropping out. Of note, 4 treatment-emergent adverse events (TEAEs) led to treatment discontinuation.

"As reported in May of this year, in preclinical testing, we have discovered strong Nurr1 agonism by vidofludimus calcium. The known characteristics of Nurr1 activation suggest broad therapeutic potential in neurodegenerative pathologies including MS,” Andreas Muehler, MD, chief medical officer at Immunic, said in a statement.¹ "The neuroprotective properties of vidofludimus calcium were already identified in our phase 2 EMPhASIS trial of vidofludimus calcium in relapsing-remitting MS, by showing an initial signal for prevention of confirmed disability worsening, as reported in November of last year."

He added, “We look forward to reporting the interim analysis of our CALLIPER trial, expected in the fall of this year, to assess biomarkers that have been shown in third-party research to consistently correlate with disease activity in neurodegenerative disorders."

REFERENCES
1. Immunic completes enrollment of its phase 2 CALLIPER trial of vidofludimus calcium in progressive multiple sclerosis. News release. Immunic. August 17, 2023. Accessed August 17, 2023. https://www.prnewswire.com/news-releases/immunic-completes-enrollment-of-its-phase-2-calliper-trial-of-vidofludimus-calcium-in-progressive-multiple-sclerosis-301903416.html#:~:text=(Nasdaq%3A%20IMUX)%2C%20a,838)%2C%20in%20patients%20with%20progressive
2. Immunic announces FDA clearance to begin IMU-838 phase 3 ENSURE studies in relapsing-remitting multiple sclerosis and phase 2 CALLIPER study in progressive multiple sclerosis. News release. July 1, 2021. Accessed August 17, 2023. https://www.immunic-therapeutics.com/2021/07/01/immunic-inc-announces-fda-clearance-to-begin-imu-838-phase-3-ensure-studies-in-relapsing-remitting-multiple-sclerosis-and-phase-2-calliper-study-in-progressive-multiple-sclerosis/
3. Fox RJ, Wolf C, ONdrus M, Sciacca V, Muehler A. Assessment of long-term safety and tolerability of vidofludimus calcium in patients with relapsing-remitting multiple sclerosis in the open-label extension period of the phase 2 trial (EMPhASIS). Presented at: 2023 CMSC Annual Meeting; May 31 to June 3; Aurora, CO. Abstract DMT51