Date: 2011-11-07
Type of information: Results
phase: 2b
Announcement:
Company: 4SC (Germany)
Product: Vidofludimus
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: rheumatoid arthritis Therapeutic
area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases Country: Poland, Romania, Bulgaria, 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 patients. The primary endpoint of this study is the estimation of ACR20 at week 13, 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 35 mg of vidofludimus given orally once-daily plus MTX, 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 has presented final results from its clinical Phase IIb COMPONENT study with 4SC\'s anti-inflammatory compound vidofludimus in rheumatoid arthritis at the annual scientific meeting of the American College of Rheumatology (ACR) in Chicago, USA. The international, multi-centre, randomised, placebo-controlled study evaluated the efficacy of vidofludimus in combination with methotrexate (MTX) (treatment group), compared to MTX alone (placebo group), in 241 rheumatoid arthritis patients. As previously announced in the study's topline results on 8 June 2011, vidofludimus improved all ACR scores (ACR20, ACR50, ACR70), but - with an improvement of 50.8% in the treatment group vs. 44.8% in the placebo group - missed the study\'s primary efficacy endpoint of improving ACR20 with statistical significance. The general anti-inflammatory activity of vidofludimus in the COMPONENT study is supported further by statistically significant differences in various efficacy endpoints (ACR20/DAS28) at specific time points between treatment and placebo group. Thus, ACR20 response improvement of the 35 mg vidofludimus group compared to placebo was statistically significant (p<0.05) at week 8 (46.7% vs. 31.9%). Time to ACR20 response was significantly (p<0.05) shorter in the vidofludimus group compared to placebo (median 56 days vs. 92 days). In addition, the rate of DAS28 (CRP), another secondary efficacy endpoint, was significantly (p<0.05) higher in the vidofludimus group compared to placebo at week 4 (55.0% vs. 41.3%). However, the difference was not statistically significant at week 13 (60.9% vs. 56.9%). Further results show that mean changes of rheumatoid arthritis -specific parameters which are mainly based on physicians' and patients' subjective assessments (including pain intensity, patients' and physicians' assessment of disease activity, tender and swollen joint counts, and HAQ-DI) were similar in both groups at week 13, although all ACR/DAS scores were numerically higher in the vidofludimus group compared to placebo and even significantly superior at specific time points. In addition, a statistically significant negative influence of MTX dosing on vidofludimus plasma levels was observed; this might have been a reason why the full anti-inflammatory activity of vidofludimus could not be fully shown in this study since patients demonstrated to have increased ACR20 response with increasing vidofludimus plasma levels.
Final evaluation of the full data set of the COMPONENT study now revealed that vidofludimus showed a substantial anti-inflammatory activity in rheumatoid arthritis patients. This is in particular supported by decreases of objective inflammatory parameters comprising the biomarkers C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) in the vidofludimus treatment arm compared to placebo. Group comparison of mean CRP change at week 13 compared to baseline was a reduction of 1.82 mg/l for vidofludimus whereas in contrast an increase of 1.38 mg/l was recorded for placebo. Group comparison of mean ESR change at week 13 compared to baseline was a reduction of 3.98 mm/h for vidofludimus while an increase of 3.18 mm/h was detected for placebo. These results strongly confirm the drug's broad potential in autoimmune diseases including in particular IBD, an indication in which vidofludimus generated very positive results in a Phase IIa clinical trial (the ENTRANCE study).
