Trials of IMU-838 in RRMS, Progressive MS Start Later This Year

The U.S. Food and Drug Administration has cleared Immunic Therapeutics to initiate two clinical trials of its investigational medication IMU-838 (vidofludimus calcium) in people with relapsing-remitting multiple sclerosis (RRMS), as well as a separate trial for people with progressive types of MS.

The RRMS clinical trial program, expected to begin in the coming months, will consist of two identically-designed Phase 3 trials, dubbed ENSURE-1 and ENSURE-2. If results from the trials are positive they are expected to support applications for regulatory approval of IMU-838 as a treatment for RRMS.

The FDA’s clearance to begin the trials “is yet another seminal moment for Immunic as it progresses our lead asset, IMU-838, into a pivotal program and heralds the final phase of clinical development in MS,” Daniel Vitt, PhD, the company’s president and CEO, said in a press release.

ENSURE-1 and ENSURE-2 will be conducted at more than 100 sites in 14 countries, including the United States, Latin America, Central and Eastern Europe, and India. Each of the trials is expected to enroll approximately 1,050 patients and assign them randomly to receive IMU-838 (30 mg) or a placebo, taken by mouth once per day for about 72 weeks (about a year-and-a-half). The 30 mg dosage is based on findings from a prior analysis.

The study’s main goal is to determine if IMU-838 is better than a placebo at delaying the time to a first relapse. Disability progression, changes in cognition and brain lesions, and measures of brain volume also will be assessed.

“We believe that the Phase 3 ENSURE program meaningfully simplifies IMU-838’s regulatory approval path in MS as it applies a very clean and straightforward study design,” Vitt said.

“In our discussions with regulatory authorities, including the FDA and the European Medicines Agency, testing IMU-838 against placebo was viewed as a reasonable approach for our Phase 3 program, from both a regulatory and scientific perspective,” added Andreas Muehler, MD, chief medical officer at Immunic.

Enrollment in the CALLIPER Phase 2 clinical trial also is expected to start later this year. It is expected to enroll about 450 people with progressive types of MS, which includes primary progressive MS (PPMS) and secondary progressive MS (SPMS). The trial will take place at more than 70 sites in North America and Europe.

Participants in CALLIPER will be given either 45 mg IMU-838 or a placebo once daily. The trial’s main goal is to assess the effect of treatment on brain volume up to 120 weeks (over two years). Disability-related measures also will be assessed.

“We designed the CALLIPER trial to study patients who currently are not typically treated with relapse preventing therapies. Our goal is to highlight IMU-838 as a therapy that combines truly differentiated safety and tolerability with neuroprotective activity such as slowing of brain atrophy and disability worsening,” Vitt said. “In our view, success in the CALLIPER trial could provide an important differentiator for IMU-838 in the MS market.”

In both the ENSURE and CALLIPER trials, interim analyses will be done after certain milestones are met — to look at relapse rates in ENSURE, and to assess a marker of nerve cell damage called neurofilament light chain (NfL) in CALLIPER.

IMU-838 is designed to block the metabolism of active T-cells and B-cells. These immune cells help to drive the inflammation that causes nervous system damage in MS. Of note, because it is specifically designed to target active cells — immune cells that are actively participating in inflammation — IMU-838 is not expected to substantially affect the parts of the immune system that defend against infection.

IMU-838 has been tested in Phase 1 trials, and the Phase 2 clinical trial EMPhASIS (NCT03846219) evaluated the medication in 269 adults with RRMS. Results from EMPhASIS indicated that treatment with 30 mg IMU-838 significantly reduced the number of brain lesions after about six months, relative to a placebo. No major safety issues were reported.

“IMU-838’s phase 2 results in relapsing-remitting multiple sclerosis showed an encouraging balance between efficacy, safety, and tolerability and I look forward to the Phase 3 program in this indication,” said Robert J. Fox, MD, a neurologist at the Mellen Center for Multiple Sclerosis in Cleveland, Ohio, and coordinating investigator of the ENSURE and CALLIPER programs.

“Based on its very strong safety and tolerability profile along with its robust efficacy, which we are planning to further highlight with neuroprotective data from the CALLIPER trial, we believe that IMU-838 has the potential to become a well-differentiated new treatment option for MS patients,” Muehler said.