Disease modifying therapyThursday, September 28, 2006, 15:30 - 17:00
BG00012, a novel oral fumarate, is effective in patients with relapsing-remitting multiple sclerosisL. Kappos, D.H. Miller, D.G. MacManus, R. Gold, E. Havrdova, V. Limmroth, C.H. Polman, K. Schmierer, T.A. Yousry, M. Yang, M. Eraksoy, E. Meluzinova, I. Rektor, G. O'Neill (Basel, CH; London, GB; Gottingen, D; Prague, CZ; Cologne, D; Amsterdam, NL; Cambridge, USA; Istanbul, TR; Brno, CZ)
Background: There is a need for more effective and more easily administered treatments in patients with multiple sclerosis (MS). Results of a phase 3 study showed that BG00012, a novel oral fumaric acid ester, is an effective treatment for chronic plaque psoriasis. Preliminary results from another study indicated that BG00012 may also be effective in patients with relapsing-remitting MS (RRMS). Here, we report the results of a randomised, double-blind, placebo-controlled, dose-ranging phase 2b study conducted to determine the efficacy of three dose levels of BG00012 on disease activity as reflected by the accumulation of new lesions on serial magnetic resonance imaging (MRI) in patients with RRMS.
Methods: Patients 18 to 55 years of age with a diagnosis of RRMS and an Expanded Disability Status Scale score between 0.0 and 5.0 were eligible. In addition, eligible patients were required to have either >=1 relapse within 12 months prior to randomisation or >=1 gadolinium-enhancing (Gd+) lesion on cranial MRI at the time of screening. During a 24-week treatment period patients received one of four treatments: BG00012 capsules 120 mg by mouth once daily (120 mg/day), 120 mg three times daily (tid) (360 mg/day), 240 mg tid (720 mg/day), or placebo. All patients then received BG00012 during a 24-week dose-blinded safety-extension period. The primary end point was the total number of Gd+ lesions, calculated as the sum of four MRI scans at Weeks 12, 16, 20, and 24. Additional MRI end points included the cumulative number of new Gd+ lesions from baseline to Week 24, the number of new and enlarging T2-hyperintense lesions at Week 24, and the number of new T1-hypointense lesions at Week 24. Relapses and disability progression were also assessed.
Results: A total of 257 patients were evenly randomised to the four treatment groups. Compared with placebo, treatment with BG00012 240 mg tid led to a 69% reduction in the total number of Gd+ lesions on scans acquired at Weeks 12 to 24 (4.5 ± 7.4 vs 1.4 ± 3.8; P<0.001), and a reduction in the number of new and enlarging T2-hyperintense (4.2 ± 5.4 vs 2.2 ± 5.4; P<0.001) and of new T1-hypointense lesions (1.7 ± 2.5 vs 0.8 ± 2.0; P=0.014). In addition, a 32% reduction in relapse rate was observed, however this effect was not significant.
Conclusion: BG00012 significantly reduced MRI-detectable brain lesion activity in patients with RRMS over 24 weeks of treatment.