Date: 2012-06-18
Type of information: Publication of results in a medical journal
phase: preclinical
Announcement: publication of preclinical data in Transplantation (15 June 2012, Volume 93, Issue 11, p. 1101-1107).
\'Immunosuppression with 4SC-101, a novel inhibitor of dihydroorotate dehydrogenase, in a rat model of renal transplantation\'. Krisztina Rusai et al.
Company: 4SC (Germany)
Product: vidofludimus (4SC-101)
Action
mechanism: 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 IFN-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.
Disease: kidney transplantation
Therapeutic area: Transplantation
Country:
Trial details:
Latest
news: 4SC AG, a discovery and development company of targeted small molecule drugs for autoimmune diseases and cancer, has announces that new preclinical data featuring its lead autoimmune product vidofludimus (4SC-101) have been published in a peer-reviewed article in scientific journal Transplantation.
The data show that vidofludimus prolongs survival after kidney transplantation paralleled by amelioration of histological signs of acute transplant rejection in a preclinical model. Furthermore, in a remnant kidney model vidofludimus had no worsening effects on kidney function and even showed protective effects on kidneys by slowing kidney fibrosis. Vidofludimus, an oral inhibitor of IL-17A and IL-17F and of DHODH, has demonstrated strong anti-inflammatory activity and good safety in several preclinical and clinical studies in various autoimmu ne indications. 4SC is currently engaging in talks with potential partners to prepare a Phase IIb study with vidofludimus in the indication inflammatory bowel disease (IBD).
The data published in the current issue of Transplantation demonstrate that animals treated with vidofludimus after a kidney transplantation showed significantly longer survival than placebo treated animals (p<0.001). That effect was paralleled by less severe histological features of acute kidney rejection 3 and 5 days after the transplantation: In the vidofludimus treatment group the invasion of immune cells into the transplanted tissue (interstitial and perivascular infiltration) as well as observed inflammation of the kidney tubules (tubulitis) were considerably lower compared to the placebo group. In addition, 5 days after transplantation lower levels of the pro-inflammatory cytokine IL-17 were expressed in the vidofludimus group compared to placebo treated animals.
Since in the past many immunosuppressant agents administered in transplantation medicine have shown toxic effects on kidneys, the impact of vidofludimus on kidney function was investigated in a preclinical model. In this remnant (5/6 nephrectomy) kidney model, vidofludimus was shown to have a protective effect on kidney cells and to improve certain kidney functions. In detail, vidofludimus compared to placebo reduced proteinuria, glomerulo sclerosis and kidney tissue fibrosis. Generally, vidofludimus reduced the infiltration of immune cells (T lymphocytes and macrophages) in the kidney tissue and caused a significant reduction of IL-17 levels. These findings indicate that these mechanisms were most probably responsible for ameliorated acute rejection after kidney transplantation.
Dr. Ulrich Dauer, CEO of 4SC AG said: \'These novel preclinical data in a transplant rejection model now published in Transplantation, once again demonstrate the broad potential of vidofludimus as a novel therapy for autoimmune diseases and chronic inflammation. Vidofludimus was able to prolong the survival time and ameliorate features of acute rejection after kidney transplantation in a preclinical model. Therefore, vidofludimus seems to be a promising immunomodulatory drug also in transplantation medicine. Since vidofludimus has been shown to be safe in several human clinical trials already, clinical development of vidofludimus in transplantation medicine might be a further therapeutic option in the future. The published data also reinforce our planned clinical Phase IIb study in IBD which we are currently preparing in talks with regulatory authorities and potential partners\'.
