Interim Analysis of Phase 1b Trial Does Not Show Desired Activity for Patients with Psoriasis

IMU-935 is a highly potent and selective inverse agonist of retinoic acid receptor-related orphan nuclear receptor gamma/truncated.

A pre-planned interim analysis of a phase 1b clinical trial investigating IMU-935 in patients with moderate-to-severe psoriasis did not show the desired results, according to a press release from Immunic, Inc.

The analysis found that the group averages for Psoriasis Area and Severity Index (PASI) reductions in the 2 active arms did not separate from placebo at 4 weeks. Although the active arms did perform in line with prior expectations, the investigators noted a greater PASI decrease than expected in the placebo arm based on similarly designed trials.

“The unexpected high placebo rates observed in this interim analysis are disappointing and confound the evaluation of activity in the investigated active treatment arms,” said Andreas Muehler, MD, chief medical officer of Immunic, in the press release. “This requires further investigation throughout the coming weeks and months.”

IMU-935 is a highly potent and selective inverse agonist of retinoic acid receptor-related orphan nuclear receptor gamma/truncated (RORγt), which is believed to be the main driver for the differentiation of TH17 cells and the release of cytokines involved in various inflammatory and autoimmune diseases. The target is believed to be a potential alternative to approved antibodies for targets, such as interleukin (IL)-23, the IL-17 receptor, and IL-17 itself.

IMU-935 showed strong cytokine inhibition, targeting both Th1 and Th17 responses in preclinical testing, in addition to indications of activity in animal models for psoriasis, graft-versus-host disease, multiple sclerosis, and inflammatory bowel disease. Preclinical experiments also indicated that IMU-935 did not affect thymocyte maturation.

A phase 1 clinical trial evaluating single and multiple ascending doses in healthy human subjects showed a favorable safety, tolerability, and pharmacokinetic profile of IMU-935.

The trial was structured as a 28-day, double-blind, placebo-controlled trial and was conducted in Australia, New Zealand, and Bulgaria. A total of 41 patients were enrolled and the trial evaluated IMU-935 at doses of 150 mg once-daily and 150 mg twice-daily versus placebo. The primary objective was the safety and tolerability of IMU-935 in patients with moderate-to-severe psoriasis.

At this point, the press release noted that the company has very limited information. The interim analysis only revealed mean values at group-level up to the end of the 4-week treatment period. The company does not yet have access to unblinded individual patient data. In addition, pharmacodynamic, biomarker, and pharmacokinetic data are still unavailable at both the individual and group levels.

“Availability of the full, unblinded individual patient data, and in particular the quantitative immunological markers, should help us to further guide the optimal development path for IMU-935,” Muehler said in the press release.

Based on the available preclinical and clinical safety and tolerability data, Immunic could consider additional higher-dose or longer treatment cohorts. The company said it continues to believe in the investigative treatment’s potential therapeutic activity based on data from in vitro and in vivo studies in various disease models and settings, according to the press release.

“Although we did not see the desired activity signal over placebo in this group-level interim analysis, we retain a high degree of conviction on IMU-935’s potential promise in psoriasis and beyond,” said Daniel Vitt, PhD, CEO, and president of Immunic, in the press release. “Given the proven binding of IMU-935 to the molecular target of RORγt, potent target inhibition as measured by transcription inhibition and secretion of pro-inflammatory cytokines, including IL-17A, IL-17F, and IFNγ from human peripheral blood mononuclear cells, proven inhibition of Th17 cell differentiation, and consistent activity in different animal models, including psoriasis, multiple sclerosis, and graft-versus-host disease, we believe IMU-935 holds the potential to provide a safe, efficacious, and meaningful treatment option to patients with psoriasis.”

REFERENCE

Immunic Reports Pre-Planned Phase 1b Interim Analysis of IMU-935 in Psoriasis Patients Confounded by High Placebo Rate. News release. Immunic Therapeutics; October 20, 2022. Accessed October 27, 2022. https://ir.imux.com/2022-10-20-Immunic-Reports-Pre-Planned-Phase-1b-Interim-Analysis-of-IMU-935-in-Psoriasis-Patients-Confounded-by-High-Placebo-Rate