Additional Group of RRMS Patients Sought to Take Lower Dose of IMU-838 in Phase 2 Trial

Immunic Therapeutics is seeking 60 more adults with relapsing-remitting multiple sclerosis (RRMS) to test a lower dose of IMU-838, its leading oral experimental therapy, in its ongoing Phase 2 EMPhASIS trial.

The decision was based on previous trial results showing that both doses tested (30 and 45 mg per day) appeared to be equally safe and effective at lowering the number of brain lesions in RRMS patients, supporting the use of the lower dose in a future Phase 3 clinical trial.

“IMU-838 demonstrated robust efficacy, through the achievement of all primary and key secondary [goals], combined with an outstanding safety and tolerability profile,” Daniel Vitt, PhD, Immunic’s CEO and president, said in a press release.

“We believe that the Phase 2 results emphasize the game-changing potential of IMU-838 as a once-daily oral therapy for this indication,” Vitt said.

The new group of patients in EMPhASIS (NCT03846219), to be enrolled in still-active sites across Eastern Europe, will receive a daily dose of either 10 mg of IMU-838 or a placebo. This group is meant to provide additional data on the therapy’s dose response and address any potential regulatory requests regarding the Phase 3 trial’s design.

Immunic plans to submit meeting requests focused on EMPhASIS results (including from the new patient group) and propose the therapy’s Phase 3 program to regulatory authorities by March 2021. The end-of-Phase 2 meetings are expected to be held around May next year.

IMU-838 (vidofludimus calcium) is a small molecule that works by blocking the activity of dihydroorotate dehydrogenase (DHODH), an enzyme required for the activity of B-cells and T-cells — immune cells that drive inflammation that can damage the nervous system in MS. As such, IMU-838 is thought to suppress the activity of these cells and prevent further damage.

The Phase 2 EMPhASIS study was designed to evaluate IMU-838’s safety and effectiveness in more than 200 adults with active RRMS, recruited across Eastern Europe. Disease activity was assessed through clinical evidence of relapse and signs of active brain lesions on MRI scans.

Participants were assigned randomly to receive either 30 mg (69 patients) or 45 mg (71 patients) of IMU-838, or a placebo (69 patients), given orally once daily for 24 weeks (nearly six months).

In August, Immunic announced top-line results showing that the trial had met its main and key secondary goals, with both doses of IMU-838 significantly dropping the number of active brain lesions, compared with a placebo — by 62% with the higher dose ,and by 70% with the lower dose.

EMPhASIS’ full data, shared in September and summarized in a poster presentation at the MSVirtual2020 conference, confirmed and expanded on the previous findings, highlighting that the trial met all its goals.

There was a consistent effect for brain lesion suppression across different patient populations, and reduction of lesions was already present at six weeks (first assessment). All other secondary goals showed signs of IMU-838’s therapeutic benefits.

Notably, both IMU-838 doses resulted in a robust decrease in the blood levels of neurofilament light chain (NfL; a biomarker of neurodegeneration) — by 17.% with the lower dose and by 20.5% with the higher dose —, while placebo was associated with a small 6.5% raise in NfL levels. These findings support IMU-838’s potential neuroprotective properties.

The therapy was generally safe and well tolerated, with comparable lower rates of adverse events (side effects) and treatment discontinuation between therapy and placebo groups. There also were no signs of liver or kidney function damage with the therapy.

According to the presentation, IMU-838’s effects on brain lesions were comparable or superior to other first-line and oral therapies approved for RRMS, and the absence of relevant adverse events leading to treatment discontinuations distinguishes it from other oral RRMS treatments.

Participants completing the 24-week treatment were given the option to enter the trial’s open-label, long-term extension phase, in which all will continue or switch from placebo to IMU-838 treatment for up to nine-and-a-half years.

Considering that both doses appeared to have comparable safety and effectiveness, Immunic likely will propose IMU-838’s lower dose (30 mg per day) for evaluation in its future Phase 3 program, whose preparation is already underway.

However, since data from a lower dose in the effective dose range would be beneficial to complete IMU-838’s dose-effect assessment in RRMS patients, Immunic initiated the small sub-trial within EMPhASIS to now test a 10 mg dose in 60 adults with RRMS.

IMU-838 also is being evaluated as a potential treatment for other diseases in which an overactive immune system is thought to cause damage, including ulcerative colitis (a type of inflammatory bowel disease), primary sclerosing cholangitis, and COVID-19.