Interim data from a Phase 2 trial of Immunic Therapeutics’ investigational oral therapy IMU-838 (vidofludimus calcium) in relapsing-remitting multiple sclerosis (RRMS) patients has established a once-daily, 30 mg dose as the most appropriate for future Phase 3 trials.
The company is now in discussions with regulatory authorities, including those in the U.S. and Europe, regarding pivotal Phase 3 testing expected to start later this year.
At the request of the U.S. Food and Drug Administration (FDA), Immunic will directly submit an investigational new drug (IND) application for the right to open a Phase 3 trial, instead of waiting for an end-of-Phase 2 meeting, it reported in a press release.
“Data thus far continues to convince us that IMU-838 may become an important, new, oral therapeutic option with an outstanding combination of safety, tolerability and robust efficacy for the treatment of patients suffering from RRMS, and we are eager to move ahead with its final clinical development steps,” said Daniel Vitt, PhD, chief executive officer and president of Immunic.
“We look forward to announcing details for the design of our phase 3 program, which we intend to initiate in the second half of this year, as soon as the final regulatory feedback is available,” he added.
IMU-838 is designed to block the metabolism of active immune T- and B-cells, which modulates their activity and function. These immune cells are thought to take part in the mistaken autoimmune attack on myelin — the coating that protects the nerve fibers — causing a variety of MS symptoms.
While IMU-838 suppresses active cells, it largely leaves other immune cells unaffected to allow the immune system to continue to fight infections. Previous studies demonstrated that IMU-838 did not increase infection rates over a placebo, Immunic reports.
The tablet treatment was tested in two Phase 1 trials, and is under investigation in the EMPhASIS Phase 2 trial (NCT03846219), which enrolled 209 adults with RRMS and active disease at 38 centers across Eastern Europe. This trial concluded its placebo-controlled main study in mid-2020; enrolled patients were invited to continue or start treatment in a multi-year, open-label extension.
Participants in the main trial were randomly assigned to one of two doses of IMU-838 — 30 mg or 45 mg — or to a placebo once daily for 24 weeks (about six months). The primary goal was a reduction in the number of active brain lesions on an MRI scan at the end of treatment.
Top-line results from this group of patients (197 completed the trial as cohort 1) showed that both IMU-838 doses resulted in a similar and significant reduction in the number of active brain lesions. Compared with a placebo, patients taking the high dose had 62% fewer active brain lesions, and those on the low dose a 70% reduction.
The two doses also significantly lowered the levels of neurofilament light chain (a maker of nerve cell damage), and raised no safety issues, with the rates of side effects being comparable between treatment and placebo groups.
To confirm that a lower dose would not match the efficacy of the 30 and 45 mg doses in RRMS patients, Immunic decided to expand the EMPhASIS trial last year, adding 60 patients (as cohort 2), who were randomly assigned to a 10 mg dose or a placebo for 24 weeks.
Interim data from the 59 patients who completed the first 12 weeks of treatment has confirmed that a lower dose resulted in smaller benefits in lesion suppression, compared with the previously tested higher doses.
At the 12-week assessment, cohort 1 patients had experienced a 62%–75% reduction in their active MRI lesions compared with a placebo. That reduction was of 32%–40% with the 10 mg dose, confirming that the 30 mg dose is the most appropriate for future trials.
“The positive outcome of the interim analysis of our Cohort 2 sub-trial of IMU-838 in RRMS further strengthens our understanding of the dose-response relationship of IMU-838,” said Andreas Muehler, MD, chief medical officer of Immunic.
“The 10 mg interim data and its comparison to the already available 30 mg and 45 mg data provide additional support to address potential regulatory requests in the context of the design and execution of our Phase 3 program,” Muehler added.
“Based on all available data, we believe that the dose of 30 mg once daily IMU-838 should be considered the most appropriate dose for RRMS patients,” he said.
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