Type of information:
Company: Medigene (Germany)
Action mechanism: RhuDex® is a CD80 antagonist that blocks undesired T-cell activation and thus has an immunomodulating and anti-inflammatory effect. Therefore, this drug candidate can be classified with the group of “Disease-Modifying Antirheumatic Drugs” (DMARDs). In a phase IIa trial in 29 patients in the indication rheumatoid arthritis, RhuDex® showed initial signs of biological activity.
Disease: primary biliary cirrhosis
Therapeutic area: Autoimmune diseases - Inflammatory diseases - Liver diseases - Rheumatic diseases
details: RhuDex® RapidFACT™ formulation study: During the recently completed clinical formulation study, variations of a RhuDex® formulation were given subsequently in single dose applications to ten healthy volunteers. Due to the innovative RapidFACT™ (Rapid Formulation Development and Clinical Testing) study design, variants of formulations could be tested and evaluated for their tolerability and pharmacokinetic profile over a short period of time, since the respective formulation variant was produced immediately prior to dosing. All formulations investigated showed an excellent tolerability profile. The final formulation demonstrates the most advantageous prolongation of plasma absorption and elimination phases to achieve steady compound plasma levels with repeat daily dosing. Due to the highly flexible study design, additional preliminary data on the effect of concomitant food intake (\"food effect\") and on dose proportionality have also been obtained.
Dr. Frank Mathias, CEO of Medigene AG, comments: „Medigene has developed a logical and integrated non-clinical and clinical program for RhuDex®. We have a new, optimized formulation for this candidate and now want to prove the clinical relevance of RhuDex®’s mode of action as quickly as possible. The PBC indication offers an extremely useful and rapid way to achieve this goal. The results will be highly valuable for the further development of RhuDex® in the treatment of rheumatoid arthritis.\"
The objective of the clinical formulation trial was to develop an optimized oral formulation of the active substance suitable for the treatment of chronic diseases. All endpoints of the study were met. The new formulation is characterized by an optimized pharmacokinetic profile, excellent tolerability and a reduction of dose units. Based on the results of this study, RhuDex® will now be administered in a formulation based on Gelucire. This excipient is a known lipid-based compound belonging to the group of excipients \"generally regarded as safe\" (GRAS), and is used in marketed drug formulations.
With the new formulation, Medigene plans to initiate a phase II clinical proof-of-concept study with RhuDex® for the treatment of autoimmune diseases. Medigene will conduct this study in the indication of primary biliary cirrhosis (PBC), allowing the company to generate widely accepted clinical data on relevant disease parameter modification after only three months of treatment. In addition, patients with PBC do not receive explicit immunomodulating baseline therapy, as is the case, for example, in the treatment of rheumatoid arthritis. Thus, this patient group is suitable to preliminarily confirm that RhuDex®, due to its specific mode of action, does not adversely affect the ability to mount a spontaneous inflammatory reaction. Therefore, this clinical study is an important step for the further development of RhuDex® in the treatment of rheumatoid arthritis.
In parallel to the planned initiation of this proof-of-concept study, Medigene has initiated additional regulatory non-clinical studies to enable the necessary chronic treatment of patients with autoimmune diseases. Also, non-clinical studies are being conducted to integrate additional translational aspects into clinical development.