Nearly 95% of patients treated with vidofludimus calcium were free from 12-week confirmed disability worsening events at week 96 of the open-label extension trial.
Newly 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 disability worsening (CDW) over time in patients with relapsing multiple sclerosis (MS).1,2
EMPhASIS included a 24-week blinded treatment period where IMU-838 was assessed in doses of 10, 30, and 45 mg, followed by an optional long-term extension (OLE) phase running 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 the active drug.
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.
"The newly obtained data from our phase 2 EMPhASIS trial of vidofludimus calcium in RRMS patients demonstrate an encouraging signal in preventing 12-week and 24-week confirmed disability worsening events as compared to placebo during the double-blind treatment phase," Daniel Vitt, PhD, chief executive officer, and president, 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) 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.
In addition to findings from EMPhASIS, Immunic hosted a panel of MS experts, who presented various research abstracts, including antiviral data on IMU-838. It had been previously suggested that Epstein-Barr virus (EBV) is essential for onset of MS and involved in autoimmunity. Additionally, EBV antibody titers have been shown to be higher in MRI-active patients with MS. Because of its ability to inhibit dihydroorotate dehydrogenase (DHODH), IMU-838 could potentially provide broad-spectrum antiviral activity against different pathogenic virsus, including EBV.
While viruses typically relay on the host cell’s infrastructure for replication, this inhibition leads to a depletion of pyrimidine nucleotides that are needed for the production of viral RNA and DNA, and production of viral proteins. By targeting the host cell metabolism, the agent has shown to be active against different RNA and DNA viruses in vitro including strong anti-EBV activity.
With each reactivation and infection cycle, a newly generated humoral response bears the risk of newly generated cross-reactive antibodies by a process called somatic hypermutation. IMU-838 can block the recurrent reactivation cycle of EBV, opening up potential long-term benefit through reduction of the constant neurodestructive trigger of EBV. In a previous analysis, treatment with IMU-838 resulted in a concentration-dependent anti-EBV activity with an IC50 of 3.3 uM, as well as produced a concentration-dependent reduction of the immediate early antigen, Zta.
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.