Newly reported interim information from the section 2 EMPhASIS trial (NCT03846219) of Immunic’s investigational agent, vidofludimus calcium (IMU-838), confirmed that remedy with the remedy was related to a low fee of confirmed incapacity worsening (CDW) over time in sufferers with relapsing a number of sclerosis (MS).1,2
EMPhASIS included a 24-week blinded remedy interval the place IMU-838 was assessed in doses of 10, 30, and 45 mg, adopted by an non-obligatory long-term extension (OLE) section working as much as 9.5 years. The interim evaluation was carried out with information extraction in October 2022, when 209 sufferers remained on remedy within the OLE, a few of whom had already obtained greater than 180 steady weeks of the lively drug.
A set off occasion was an Expanded Incapacity Standing Scale (EDSS) rating enhance of at the very least 1.5 factors if baseline is 0, of at the very least 1.0 factors if baseline EDSS is 1-5, and of at the very least 0.5 factors if baseline EDSS was higher than 5.5 . Within the OLE, 97.6% of sufferers handled with IMU-838 have been free from 12-week CDW occasions after 48 weeks of remedy and 94.5% after 96 weeks. Comparable outcomes have been noticed for 24-week CDW and sustained CDW.
“The newly obtained information from our section 2 EMPhASIS trial of vidofludimus calcium in RRMS sufferers reveal an encouraging sign in stopping 12-week and 24-week confirmed incapacity worsening occasions as in comparison with placebo in the course of the double-blind remedy section,” Daniel Vitt, PhD, chief government officer, and president, Immunic, stated in an announcement.1 “We sit up for receiving additional, confirmatory information from our section 3 ENSURE program in relapsing MS in addition to our section 2 CALLIPER trial in progressive MS.”
The 12-week CDW of two.8% for IMU-838 after 1 12 months was additionally much like different historic trials. In relapsing-remitting MS, teriflunomide (Aubagio; Sanofi) demonstrated charges of seven.2% and 10.8% within the OPTIMUM and ASCLEPIOS trials, whereas ocrelizumab (Ocrevus; Novarits) and ofatumumab (Kesimpta; Novartis) confirmed charges of seven.1% and 6.6%, respectively. Equally, ponesimod and interferon ß-1a resulted in 12-week CDW charges of 6.5% and eight.6%, respectively.
Along with findings from EMPhASIS, Immunic hosted a panel of MS consultants, who offered varied analysis abstracts, together with antiviral information on IMU-838. It had been beforehand prompt that Epstein-Barr virus (EBV) is important for onset of MS and concerned in autoimmunity. Moreover, EBV antibody titers have been proven to be larger in MRI-active sufferers with MS. Due to its means to inhibit dihydroorotate dehydrogenase (DHODH), IMU-838 may probably present broad-spectrum antiviral exercise in opposition to totally different pathogenic viruses, together with EBV.
Whereas viruses usually relay on the host cell’s infrastructure for replication, this inhibition results in a depletion of pyrimidine nucleotides which are wanted for the manufacturing of viral RNA and DNA, and manufacturing of viral proteins. By concentrating on the host cell metabolism, the agent has been proven to be lively in opposition to totally different RNA and DNA viruses in vitro together with sturdy anti-EBV exercise.
With every reactivation and an infection cycle, a newly generated humoral response bears the chance of newly generated cross-reactive antibodies by a course of referred to as somatic hypermutation. IMU-838 can block the recurrent reactivation cycle of EBV, opening up potential long-term profit by discount of the fixed neurodestructive set off of EBV. In a earlier evaluation, remedy with IMU-838 resulted in a concentration-dependent anti-EBV exercise with an IC50 of three.3 uM, in addition to produced a concentration-dependent discount of the fast early antigen, Zta.
IMU-838 remains to be at present being assessed within the section 3 ENSURE trials of relapsing MS and the CALLIPER trial of progressive MS. ENSURE-1 (NCT05134441) trial information is predicted to be readout on the finish of 2025, with ENSURE-2 (NCT05201638) quickly thereafter. CALLIPER is predicted to readout on the finish of 2024, with a deliberate interim evaluation estimated for Q2 of 2023 as soon as half of the sufferers full 24 weeks of remedy. Each of those packages are designed to place Immunic to submit a brand new drug utility for the agent in 2026.
1. Immunic studies new information from section 2 EMPhASIS trial of vidofludimus calcium in relapsing-remitting a number of sclerosis supporting the drug’s neuroprotective potential. Information launch. Immunic. November 17, 2022. Accessed November 18, 2022. 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
2. A number of Sclerosis R&D Webcast. Immunic. November 17, 2022. Accessed November 18, 2022. file:///Customers/marcomeglio/Downloads/20221117_Immunic_MS-RnD-Webcast.pdf