Positive Long-Term Safety, Low Discontinuation Rates Seen With Vidofludimus Calcium

Author(s):

Most patients completed at least 3 years of treatment, with no new safety signals observed and a treatment discontinuation rate of 5.3%.

Robert J. Fox, MD

Data from the open-label extension of the phase 2 EMPhASIS trial (NCT03846219) showed that treatment with vidofludimus calcium (Immunic), an investigational agent in development for multiple sclerosis (MS), was safe and tolerable, with some patients staying on the therapy for more than 4 years.

Vidofludimus calcium, or IMU-838, is a highly selective oral second-generation dhydroorotate dehydrogenase inhibitor designed to potentially provide broad-spectrum antiviral activity against different pathogenic viruses, including Epstein-Barr virus, which has been considered essential for onset of MS. In total, 254 individuals with relapsing-remitting MS completed the 24-week, double blind treatment period, and 209 remained on OLE treatment where they received either 30 or 45 mg of IMU-838 once daily.

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.

In the OLE, the most common TEAEs were COVID-19 (9.1%), nasopharyngitis (4.7%), back pain (2.8%), and urinary tract infection (2.0%). Investigators recorded rates of 0.023 and 0.015 per treatment year for renal and liver TEAEs, respectively. Throughout the OLE, 14 serious AEs were reported, yielding a rate of 0.027 per patient per treatment year; however, none were considered to be related to the study drug. Additionally, no new safety signals were observed and no signal for changes in hematology parameters were seen.

Prior to CMSC 2023, the latest data on the OLE of EMPhASIS was reported in November 2022, with resulting showing that the therapy was associated with a low rate of confirmed disability worsening. A trigger event was an Expanded Disability Status Scale (EDSS) score increase of at least 1.5 points if baseline is 0, of at least 1.0 points if baseline EDSS is 1-5, and of at least 0.5 points if baseline EDSS was greater than 5.5. In the OLE, 97.6% of patients treated with IMU-838 were free from 12-week CDW events after 48 weeks of treatment and 94.5% after 96 weeks. Similar results were observed for 24-week CDW and sustained CDW.²

The 12-week CDW of 2.8% for IMU-838 after 1 year was also similar to other historical trials. In relapsing-remitting MS, teriflunomide (Aubagio; Sanofi) demonstrated rates of 7.2% and 10.8% in the OPTIMUM and ASCLEPIOS trials, while ocrelizumab (Ocrevus; Novarits) and ofatumumab (Kesimpta; Novartis) showed rates of 7.1% and 6.6%, respectively. Similarly, ponesimod and interferon ß-1a resulted in 12-week CDW rates of 6.5% and 8.6%, respectively.

IMU-838 is still currently being assessed in the phase 3 ENSURE trials of relapsing MS and the CALLIPER trial of progressive MS. ENSURE-1 (NCT05134441) trial data is expected to be readout at the end of 2025, with ENSURE-2 (NCT05201638) soon thereafter. CALLIPER is expected to readout at the end of 2024, with an planned interim analysis estimated for Q2 of 2023 once half of the patients complete 24 weeks of treatment. Both of these programs are designed to position Immunic to submit a new drug application for the agent in 2026.

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REFERENCES
1. 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
2. Immunic reports new data from phase 2 EMPhASIS trial of vidofludimus calcium in relapsing-remitting multiple sclerosis supporting the drug’s neuroprotective potential. News release. Immunic. November 17, 2022. Accessed June 2, 2023. https://www.prnewswire.com/news-releases/immunic-reports-new-data-from-phase-2-emphasis-trial-of-vidofludimus-calcium-in-relapsing-remitting-multiple-sclerosis-supporting-the-drugs-neuroprotective-potential-301681124.html