Date: 2011-06-08
Type of information: Results
phase: 2b
Announcement: results
Company: 4SC (Germany)
Product: vidofludimus
Action
mechanism: 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 INF-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: rheumatoid arthritis
Therapeutic area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases
Country: 28 sites in Poland, Romania, Bulgaria and Czech Republic
Trial
details: The COMPONENT study is a randomised, double-blind, placebo-controlled, multi-centre, international Phase IIb study evaluating the efficacy of vidofludimus with methotrexate, compared to methotrexate alone, in rheumatoid arthritis (RA) patients. The primary endpoint of this study is the estimation of ACR20, secondary endpoints are ACR50, ACR70, DAS28, safety parameters and pharmacokinetics. The trial enrolled 241 patients in two study arms across 28 sites in Poland, Romania, Bulgaria and Czech Republic. In the first study arm patients received 35mg of vidofludimus given orally once-daily plus methotrexate, in the second study arm patients received placebo plus methotrexate. The study duration was 13 weeks and eligible patients must have had active RA, have received weekly doses of MTX (10-25 mg/week) for a minimum of 3 months prior to Day 1 dosing, and have received a stable MTX dose for at least 6 weeks prior to Day 1 dosing.
Latest
news: 4SC AG announced topline results from its randomised, double-blind, placebo-controlled Phase IIb clinical trial COMPONENT in RA. This compared vidofludimus, an oral inhibitor of DHODH and pro-inflammatory cytokines (including IL-17A and IL-17F as well as INF-gamma), in rheumatoid arthritis patients on methotrexate background therapy versus methotrexate monotherapy over a treatment period of 13 weeks. ACR20 response improvement of the 35 mg vidofludimus group compared to placebo was statistically significant (p<0.05) at week 2 (16.7% vs. 6.9%) and week 8 (46.7% vs. 31.9%), however, vidofludimus missed the primary endpoint of significantly improving ACR20 response at week 13 (50.0% vs. 44.8%). Time to ACR20 response was significantly (p<0.05) shorter in the vidofludimus group compared to placebo (median 56 days vs. 92 days). The patient group treated with vidofludimus also reported higher ACR50 (25.8% vs. 17.2%) and ACR70 (12.5% vs. 6%) response rates compared to placebo at week 13. Overall, vidofludimus was safe and well tolerated. No obvious differences in the adverse event rate between the vidofludimus and placebo group were observed. In particular, there were no relevant increases of diarrhea, neutropenia, anemia, hypertension, cholesterol or liver enzyme levels. Only one serious adverse event was reported in the vidofludimus group which was judged as not related to vidofludimus. No deaths occurred. These safety results were consistent with previous Phase IIa trial results in RA and inflammatory bowel disease patients 4SC will continue to analyse the current data set and the new data that will become available in the weeks ahead. The Company will use this data and data from previous trials to continue its discussions with potential partners. Meanwhile 4SC’s future development of vidofludimus will be focused on inflammatory bowel disease (IBD) and, potentially, other autoimmune indications such as lupus and psoriasis.
Vidofludimus has completed a positive Phase IIa trial in inflammatory bowel disease. In addition, various preclinical models demonstrate the application options of vidofludimus in further autoimmune indications such as lupus, psoriasis, multiple sclerosis and transplant rejection.
