February 28, 2011 02:27 AM Eastern Time
PLANEGG-MARTINSRIED, Germany–(BUSINESS WIRE)–4SC AG (Frankfurt, Prime Standard: VSC), a drug discovery and development company focused on autoimmune and cancer indications, announces the final data from the ENTRANCE Phase IIa trial in inflammatory bowel disease (IBD) with vidofludimus, an oral inhibitor of interleukin-17 (IL-17) release and DHODH, including the secondary endpoints comprising the analysis of CDAI (Crohn’s disease, CD) and CAI (ulcerative colitis, UC) disease scores, change of prednisolone intake and threshold doses, safety, pharmacokinetics and biomarkers. the data support the previously reported top-line primary endpoint result, which was achieved with a total response rate of 88.5%. these were presented last week at the 6th ECCO IBD Conference in Dublin, Ireland.
* Primary objective of the ENTRANCE study in 26 CD and UC patients was to assess vidofludimus’ remission maintenance potential in steroid-dependant IBD patients upon steroid weaning
* Primary endpoint was met with an 88.5% total response rate (complete and partial responders), supported by secondary endpoint results demonstrating a clear clinical benefit for treated IBD patients
* Required relapse-free prednisolone doses at the end of vidofludimus therapy were significantly lower than average doses needed prior to study entry * Average prednisolone consumption dramatically dropped over the course of the treatment period
* Prednisolone threshold doses of partial responders at the end of the treatment were significantly reduced compared to documented threshold doses prior to study entry
* Vidofludimus was safe and well tolerated by all patients
ENTRANCE TRIAL FINAL DATA
the top-line results from the exploratory, open-label, single-arm ENTRANCE Phase IIa study, announced in November 2010, demonstrated a 88.5% total response rate with vidofludimus versus an average placebo response rate of approximately 20% across published benchmark clinical trials, in steroid-dependant IBD patients. 53.9% (14 out of 26) of patients were complete responders, 34.6% (9 out of 26) of patients were partial responders (34.6%), and 11.5% (3 out of 26) of patients were evaluated as non-responders. no variation in response rates across the sub-disease populations of Crohn’s disease (85.7%) and ulcerative colitis (91.7%) over the 12 week treatment period was observed.
CDAI/CAI disease score development was in-line with the assignment of patients to the categories complete, partial, and non-responders. All 26 evaluable patients, excluding the three non-responders, reached a relapse-free prednisolone dose which was significantly (p<0.001) lower than their individual threshold doses at which they experienced relapses prior to entering into the study. In addition, the decrease of prednisolone intake over the 12 week treatment period indicates a strong steroid-sparing effect from vidofludimus. mean prednisolone consumption was significantly (p<0.001) lowered from 26.5 mg/day (± 8.0) at treatment start to 1.0 mg/day (± 2.7) at week 12. In addition to complete responders who by definition were in steroid-free remission at the end of the study, also partial responders experienced a significant clinical benefit. the mean prednisolone threshold dose of partial responders significantly (p<0.001) dropped from 12.5 mg/day (± 3.1) before study start to 1.4 mg/day (± 2.5) at the end of the study. As expected, due to the inclusion of patients in remission and on concomitant treatment with prednisolone, biomarker data (IL-17, C-reactive protein CRP, erythrocyte sedimentation rate ESR, and calprotectin) revealed poor or no correlation with patients’ disease activity. However, these biomarkers are expected to be valuable parameters to characterize the disease status and to potentially stratify patient populations in future IBD trials with vidofludimus.
Vidofludimus was safe and well tolerated by all patients. no clinically relevant changes of pulse rate, blood pressure, electrocardiography, body temperature, hematology and biochemistry were recorded. a total of 75 adverse events (AEs) were reported (53 mild, 18 moderate, 4 severe) of which 19 AEs were judged by investigators as ‘possibly’ or ‘probably’ drug-related. these included isolated cases of nasopharyngitis, abdominal pain, fatigue, insomnia, glucosuria, leucocyturia, microhematuria, musculoskeletal pain, myalgia, tachycardia, and dyspepsia. no drug-related serious adverse events (SAEs) were reported.
Dr Bernd Hentsch, Chief Development Officer of 4SC, commented, ‘The ENTRANCE study has produced encouraging data with vidofludimus in inflammatory bowel disease, an indication that is underserved for patients and is lacking effective and safe drugs especially in long-term remission maintenance therapy. these data provide early evidence that our oral therapy vidofludimus could provide such an alternative and we look forward to assessing the potential of this compound in further IBD trials.’
Copies of the poster are available on the 4SC website under: 4sc.de/product-pipeline/publications-posters.
Notes to Editor:
about Vidofludimus
Vidofludimus (4SC-101) 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 interleukin- 17 (IL-17), a pro-inflammatory cytokine that has a crucial pathogenic role 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.
In addition to the Phase II study in inflammatory bowel disease, Vidofludimus is also currently being evaluated in the randomised, double-blind, placebo-controlled Phase IIb COMPONENT study in patients with rheumatoid arthritis in combination with methotrexate. Preliminary results are expected to be reported in Q2 2011.
about Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) is a group of inflammatory conditions of the gastrointestinal tract. the main forms are Crohn’s disease (CD) and ulcerative colitis (UC). these chronic diseases are constituted by acute-disease flare ups which include abdominal pain, rectal bleeding, diarrhoea, weight loss, fatigue and other extra-intestinal symptoms and symptom-free phases. It is assumed that a deregulated immune response results in inflammatory mediators that attack the patient’s intestinal mucosa and trigger the symptoms. for both, CD and UC, the pro-inflammatory cytokine interleukin-17 (IL-17) has been demonstrated to play a crucial role in pathogenesis.
CD is characterised by an inflammatory affliction of part or the whole of the digestive tract and is currently incurable. Approximately 0.9 million people in the seven major industries suffer from various CD symptoms and mostly contract the disease between the ages of 20 and 40. CD leads to a considerable reduction in quality of life, but may also involve severe complications requiring immediate surgery. Current therapeutic options for patients are largely limited to the use of anti-inflammatory corticosteroids or immunosuppressants applied either systemically or locally for the treatment of the symptoms, as well as the application of biological agents (e.g. TNF-alpha targeting antibodies).
UC afflicts specifically the large intestine or colon that includes characteristic ulcers or open sores. UC occurs in approximately 1.4 million patients in the seven major industries and is currently treated with anti-inflammatory drugs, immunosuppressants and biological agents targeting specific components of the immune response. Colectomy (partial or total removal of the large bowel through surgery) is occasionally necessary and is considered to be a cure for the disease.
about 4SC
4SC AG (ISIN DE0005753818) is a drug discovery and development company focused on autoimmune and cancer indications. Vidofludimus (4SC-101), a small molecule, is currently in Phase II development in rheumatoid arthritis and inflammatory bowel disease (IBD), for which positive results from a Phase IIa study were recently reported. the company’s lead oncology compound, resminostat (4SC-201), a pan-histone deacetylase (HDAC) inhibitor, is in Phase II trials in hepatocellular carcinoma, Hodgkin’s lymphoma and KRAS-mutant colorectal cancer. two further oncology compounds, 4SC-203 and 4SC-205, are in Phase I studies. 4SC develops drug candidates until proof-of-concept in order to generate value creating partnerships with the pharmaceutical industry in return for advance and milestone payments as well as royalties.
Founded in 1997, 4SC has 94 employees and has been listed on the Prime Standard of the Frankfurt Stock Exchange since December 2005.
for further information, please visit 4sc.com.
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Language: English Company: 4SC AG am Klopferspitz 19a 82152 Martinsried Deutschland Phone: +49 (0)89 7007 63-0 Fax: +49 (0)89 7007 63-29 E-mail: Internet: ISIN: DE0005753818 WKN: 575381 Listed: Regulierter Markt in Frankfurt (Prime Standard); Freiverkehr in Berlin, Düsseldorf, München, Stuttgart