Vidofludimus Superior To Cyclophosphamide And MMF
4SC AG (Frankfurt, Prime Standard: VSC), a discovery and development company of targeted small molecule drugs for autoimmune and cancer diseases, will present pre-clinical data on vidofludimus - its lead small-molecule drug candidate against autoimmune diseases - in systemic lupus erythematosus (SLE) at EULAR 2011, Europe's largest scientific conference on rheumatic diseases, in London, UK, from May 25-28, 2011.
Vidofludimus is a novel oral inhibitor of dihydroorotate dehydrogenase (DHODH) and of pro-inflammatory cytokine release including interleukin-17 (IL-17A and IL-17F) as well as interferon-gamma which is in Phase IIb development for rheumatoid arthritis and has completed a positive Phase IIa study in inflammatory bowel disease. Additionally, the drug candidate has been demonstrated to be highly active in pre-clinical models of further autoimmune diseases such as multiple sclerosis, psoriasis, and transplant rejection. In collaboration with Prof. Dr. Hans-Joachim Anders, Medizinische Poliklinik Innenstadt, University Munich, Germany, the anti-inflammatory and immunosuppressive activity of vidofludimus was directly compared to cyclophosphamide (CYC) and mycophenolate mofetil (MMF) in an experimental animal model of SLE (MRLlpr/lpr).
Vidofludimus was as effective as CYC and MMF in inhibiting progression parameters of renal disease. Furthermore, vidofludimus improved activity and chronicity indices, markers of renal inflammation. In contrast, CYC and MMF had no significant effect on these activity indices. Treatment with vidofludimus also significantly reduced peribronchiolar inflammation, while CYC and MMF failed to achieve any protection of the lung. Vidofludimus reduced lympho-proliferation and was equipotent to CYC and superior compared to MMF. Vidofludimus also was more effective than CYC and MMF in reducing circulating plasma IL12p40 and tissue auto-antibodies (IgG). In contrast to CYC and MMF, vidofludimus showed no bone marrow toxicity effects as measured by monocyte and neutrophil counts.
These data provide evidence that delayed onset of therapy with vidofludimus is effective in suppressing immunopathology and autoimmune tissue injury of MRLlpr/lpr mice. This efficacy was comparable to CYC with respect to suppression of experimental SLE. However, vidofludimus did not cause myelosuppression like the unselective cell proliferation inhibitor CYC which may relate to the more specific mode of action of vidofludimus. Vidofludimus had a superior activity profile than MMF in this mouse model of SLE. Thus, vidofludimus may represent a novel drug that could control active SLE like CYC but avoid CYC toxicity and could, therefore, be considered for induction and maintenance therapy of SLE.
Dr Bernd Hentsch, Chief Development Officer of 4SC, commented: 'In addition to vidofludimus' primary target indications rheumatoid arthritis and inflammatory bowel disease, vidofludimus demonstrated the potential to effectively control active SLE in an experimental preclinical model without the type of side effects often seen with standard therapies. Therefore, vidofludimus could be considered to be positioned as a novel induction and maintenance therapy for lupus, an autoimmune disease with significant unmet need and poor therapeutic options available.'
About Vidofludimus Vidofludimus is a novel, orally administered small molecule for the treatment of autoimmune disorders such as rheumatoid arthritis and inflammatory bowel disease. The therapeutic efficacy of vidofludimus is based on a dual principle. Vidofludimus inhibits the expression of selected pro-inflammatory cytokines, including interleukin-17 (IL-17A and IL-17F) and interferon-gamma, that have crucial pathogenic roles in a variety of autoimmune diseases. Vidofludimus also inhibits dihydroorotate dehydrogenase (DHODH), a key enzyme of the pyrimidine biosynthesis, thereby halting the proliferation of activated T and B cells which are involved in the pathology of autoimmune disorders. The combination of two mechanisms of action provides an innovative therapeutic approach with broad clinical potential in various autoimmune diseases. Vidofludimus is currently in clinical development for rheumatoid arthritis and inflammatory bowel disease.
Source: Medical News Today