On October 20, Immunic announced that its Phase Ib clinical trial of its RORγt inverse agonist IMU-935 in the treatment of psoriasis failed to meet the primary endpoint due to a strong placebo effect.
Affected by the news, Immunic’s shares fell 74%.
IMU-935 is a highly potent and selective RORγt (retinoic acid receptor-related orphan nuclear receptor γt) inverse agonist independently developed by Immunic, which is a potential best-in-class oral IL-17 inhibitor. Studies have shown that the Th17/IL-17/RORγt axis plays an important role in the occurrence and development of autoimmune diseases, in which RORγt is the main driver of Th17 cell differentiation and secretion of proinflammatory cytokines.
IMU-935 potently inhibits cytokine release associated with Th1 and Th17 responses in preclinical studies and has been shown in animal models of psoriasis, graft-versus-host disease, multiple sclerosis, and inflammatory bowel disease. active. In addition, preclinical studies have shown that IMU-935 can effectively inhibit Th17 cell differentiation and cytokine secretion without affecting thymocyte maturation.
The Phase Ib study of the published results includes three parts, Part A is a single-dose escalation study, Part B is a multi-dose escalation study, and Part C is a validation study. Part A and Part B were performed in healthy subjects, and the results showed that IMU-935 has a favorable safety, tolerability and pharmacokinetic profile.
Part C was launched in October 2021 and enrolled 41 patients to evaluate the safety and tolerability of IMU-935 in patients with moderate to severe psoriasis. The patients in the experimental group were divided into two groups, one group received 150 mg of IMU-935 once a day, and the other group received 150 mg of IMU-935 twice a day.
Results of the interim analysis showed that at week 4 of treatment, the mean reduction in the Psoriasis Area and Severity Index (PASI) in the IMU-935 group was not significantly different from the placebo group. Although the data in the IMU-935 group were in line with expectations, the PASI reduction in the placebo group was greater than expected. In addition, IMU-935 was safe and well tolerated, and no new safety signals were observed.
Immunic said information from the results of this interim analysis was limited, revealing only group averages at the end of the 4-week treatment period, and unblinded individual patient data were not yet available. In addition, no pharmacodynamic, biomarker (including skin perforation and serum IL-17 levels) or pharmacokinetic data are available, either at the individual or group level.
Based on existing preclinical and clinical safety and tolerability data, Immunoc may consider conducting new studies with higher doses or longer treatment periods.
The company’s pipeline has a total of 4 products under development, of which 3 have entered the clinical stage, and the one with the fastest progress is IMU-838.
(vidofludimus calcium) is a dihydroorotate dehydrogenase (DHODH) inhibitor first developed by Nycomed (a subsidiary of Takeda). In July 2008, 4SC acquired 8 products including IMU-838 from Nycomed for 14 million euros. In September 2016, Immunic bought IMU-838 and IMU-366 from 4SC for $19.6 million. Currently, IMU-838 is undergoing clinical trials for relapsing multiple sclerosis (RMS), progressive multiple sclerosis (PMS) and primary sclerosing cholangitis (PSC).
Immunic also previewed some upcoming clinical data updates:
Data from the interim analysis of the Phase II CALLIPER study is expected in the second half of 2023, with key data in late 2024. This study was designed to evaluate the efficacy and safety of the dihydroorotate dehydrogenase (DHODH) inhibitor IMU-838 in patients with PMS.
First results from the Phase III ENSURE study are expected in late 2025. The study was designed to evaluate the efficacy, safety and tolerability of IMU-838 in patients with RMS.
Preliminary clinical efficacy data from Part C of the ongoing Phase I clinical trial of IMU-856 in patients with celiac disease are expected in 2023.