On Nov. 2, 2020, Immunic announced that the company had enrolled and randomized 200 patients, pre-specified in the protocol as sufficient to perform the main efficacy analysis of the phase 2 part of the CALVID-1 trial for its selective oral DHODH inhibitor, IMU-838, in hospitalized patients with moderate Coronavirus disease 2019. The trial is being conducted under an investigational new drug application granted by the U.S. Food and Drug Administration using a single global protocol with clinical sites in the United States, Germany and a range of other European countries.

The current part of CALVID-1 is defined as a phase 2 proof-of-activity trial. As per the protocol, approximately 200 patients were to be included in order to perform a main efficacy analysis which will be used, in consultation between Immunic and an Independent Data Monitoring Committee (IDMC), to assess clinical activity of IMU-838 in moderate COVID-19 based on pre-defined criteria. No formal statistical analysis was pre-specified for this main analysis and all endpoints will be analyzed descriptively. Enrollment continues while the analysis is being prepared. Apart from assessing the clinical activity of IMU-838, the main analysis of the phase 2 part of the CALVID-1 trial may also be used for sample size determination, endpoint selection and potential other trial adjustments in order to continue with a confirmatory phase 3 trial, if such continuation is warranted. The final design of the phase 3 portion will be submitted as a protocol amendment to regulatory authorities.

IMU-838 is an orally available, next-generation selective immune modulator that inhibits the intracellular metabolism of activated immune cells by blocking the enzyme dihydroorotate dehydrogenase (DHODH). IMU-838 acts on activated T and B cells while leaving other immune cells largely unaffected and allows the immune system to stay functioning, e.g. in fighting infections. In previous trials, IMU-838 did not show an increased rate of infections compared to placebo. In addition, DHODH inhibitors, such as IMU-838, are known to possess a host-based antiviral effect, which is independent with respect to specific virus proteins and their structure. Therefore, DHODH inhibition may be broadly applicable against multiple viruses. IMU-838 was successfully tested in two phase 1 clinical trials in 2017 and is currently being tested in phase 2 trials in patients with ulcerative colitis and COVID-19. The company reported positive results from its phase 2 EMPhASIS trial of IMU-838 in relapsing-remitting multiple sclerosis, achieving both primary and key secondary endpoints with high statistical significance. Furthermore, Immunic’s collaboration partner, the Mayo Clinic, has started an investigator-sponsored proof-of-concept clinical trial testing IMU-838 activity in patients with primary sclerosing cholangitis. To date, IMU-838 has already been tested in about 650 individuals and has shown an attractive pharmacokinetic, safety and tolerability profile. IMU-838 is not yet licensed or approved in any country.