1st RRMS Patient Enrolled in ENSURE-2 Trial of Oral IMU-838

The ENSURE-2 Phase 3 clinical trial, evaluating Immunic Therapeutics’ experimental oral therapy IMU-838 (vidofludimus calcium) in adults with relapsing-remitting multiple sclerosis (RRMS), has enrolled its first patient.

The milestone, announced in an email to Multiple Sclerosis News Today, follows the recruitment of the first RRMS patient in ENSURE-2’s twin Phase 3 trial, ENSURE-1 (NCT05134441), in November.

Each trial is expected to enroll up to 1,050 patients at more than 100 sites across 15 countries, including the U.S., Latin America, Europe, and India. More information on contacts and locations of ENSURE-1 can be found here; ENSURE-2’s detailed information is not yet available. ENSURE-1 is recruiting adults, ages 18-55, with active disease, defined as at least one relapse in the previous 12 months before trial treatment selections, or at least two relapses in the two previous years.

Results from both studies, should they be positive, are expected to support future submissions of regulatory applications seeking IMU-838’s approval for the treatment of RRMS.

Recommended Reading

April 15, 2021 News by Steve Bryson, PhD

Immunic Sets Optimal Dose of Oral IMU-838 for Phase 3 Trials in RRMS

IMU-838 is an orally available small molecule designed to suppress the metabolism of activated immune T-cells and B-cells, and thereby promote their death. It works by blocking an enzyme called dihydroorotate dehydrogenase.

These types of immune cells are known to drive neuroinflammation and neurodegeneration in MS. Aubagio (teriflunomide), an approved medication for relapsing forms of multiple sclerosis (MS), also works by targeting the same enzyme.

Given that IMU-838 acts on active T- and B-cells while leaving other immune cells mostly unaffected, the therapy is not expected to substantially affect the parts of the immune system that defend against infection.

Results from a previous Phase 2 trial, called EMPhASIS (NCT03846219), showed that six months of treatment with 30 mg of IMU-838 significantly reduced the number of active brain lesions in RRMS patients, compared with a placebo.

According to Immunic, this reduction was comparable to other first-line and oral treatments approved for relapsing MS.

The therapy also led to a robust drop in blood levels of neurofilament light chain, a biomarker for nerve cell damage, and raised no safety issues, with the rates of side effects being comparable between treatment and placebo groups.

In addition, there were no signals of liver toxicity or other relevant adverse events leading to treatment discontinuations, which distinguishes IMU-838 from other oral relapsing MS treatments, the company stated in the email.

Given the therapy’s placebo-like safety profile and robust anti-inflammatory and neuroprotective properties, Immunic believes IMU-838 has the potential to provide several advantages relative to other treatments.

The ENSURE clinical program consists of two identically designed Phase 3 trials evaluating the safety, tolerability, and effectiveness of the experimental therapy in adults with RRMS.

Participants are being randomly assigned to receive orally either IMU-838 (30 mg), or a placebo, once a day for 72 weeks (just short of 1.5 years).

The main goal of both studies is to assess the time to first disease relapse. Secondary goals include time to confirmed three-month disability progression, time to sustained clinically relevant cognitive changes, and changes in the volume of new brain lesions and of the overall brain. Safety measures also will be evaluated.

An interim analysis of the ENSURE trials is planned once a specified number of relapses have been recorded. This analysis also will ensure that the planned number of participants is appropriate.

IMU-838 also is being tested as potential treatment for people with progressive forms of MS, including both primary and non-active secondary progressive MS, in a placebo-controlled Phase 2 trial, called CALLIPER (NCT05054140).

The study is actively enrolling up to 450 adults, ages 18–65, at seven sites in the U.S., Bulgaria, Poland, and Ukraine; more information can be found here. About 70 sites are expected to open.