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Recently reported interim data from the Phase 2 EMPhASIS trial (NCT03846219) of Immunic’s investigational agent, vidofludimus calcium (IMU-838), showed that treatment with the therapy was associated with a low rate of confirmed worsening of disability (CDW) over time in patients with relapsing multiple sclerosis (MS).1.2
EMPhASIS included a 24-week blinded treatment period in which IMU-838 was evaluated at doses of 10, 30, and 45 mg, followed by an optional long-term extension (OLE) phase ranging from up to 9.5 years. The interim analysis was performed with data extraction in October 2022, when 209 patients remained on treatment in the OLE, some of whom had already received more than 180 continuous weeks of active drug.
A triggering event was an increase in the Expanded Disability Status Scale (EDSS) score of at least 1.5 points if the baseline score is 0, at least 1.0 points if the baseline EDSS score is 1 to 5 and at least 0.5 points if the reference EDSS score was above 5.5. . In OLE, 97.6% of patients treated with IMU-838 were free of 12-week CDW events after 48 weeks of treatment and 94.5% after 96 weeks. Similar results were seen for 24-week CDW and sustained CDW.
“Newly obtained data from our Phase 2 EMPhASIS trial of vidofludimus calcium in patients with RRMS demonstrates an encouraging signal in the prevention of confirmed disability worsening events over 12 and 24 weeks compared to placebo during the double-blind treatment phase,” Daniel Vitt, PhD, CEO and President of Immunic, said in a statement.1 “We look forward to receiving further confirmatory data from our Phase 3 ENSURE program in relapsing MS as well as our Phase 2 CALLIPER trial in progressive MS.”
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) showed 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 levels of 6.5% and 8.6%, respectively.
In addition to the EMPhASIS results, Immunic hosted a panel of MS experts, who presented various research summaries, including antiviral data on IMU-838. It had previously been suggested that the Epstein-Barr virus (EBV) is essential for the onset of MS and involved in autoimmunity. Additionally, EBV antibody titers were found to be higher in MRI-active MS patients. Due to its ability to inhibit dihydroorotate dehydrogenase (DHODH), IMU-838 could potentially provide broad-spectrum antiviral activity against different pathogenic viruses, including EBV.
While viruses generally rely on the host cell’s infrastructure for replication, this inhibition leads to a depletion of pyrimidine nucleotides necessary for the production of viral RNA and DNA and the production of viral proteins. By targeting host cell metabolism, the agent has been shown to be active against different RNA and DNA viruses in vitro including strong anti-EBV activity.
With each round of reactivation and infection, a newly generated humoral response carries the risk of newly generated cross-reacting antibodies through a process called somatic hypermutation. IMU-838 can block EBV’s recurrent reactivation cycle, unlocking potential long-term benefit through reduction of EBV’s constant neurodestructive trigger. In a previous analysis, treatment with IMU-838 resulted in concentration-dependent anti-EBV activity with an IC50 of 3.3 µM, as well as a concentration-dependent reduction in the immediate early antigen, Zta.
IMU-838 is still being evaluated in the Phase 3 ENSURE trials in relapsing MS and the CALLIPER trial in progressive MS. Data from the ENSURE-1 trial (NCT05134441) is expected to read in late 2025, with ENSURE-2 (NCT05201638) shortly thereafter. CALLIPER is expected to read at the end of 2024, with an interim analysis estimated for the second quarter of 2023 once half of the patients have completed 24 weeks of treatment. Both of these programs are designed to allow Immunic to submit a New Drug Application for the agent in 2026.
