Safety and immunogenicity of a new formulation of interferon β-1a (Rebif® New Formulation) in a Phase IIIb study in patients with relapsing multiple sclerosis: 96-week results

Background A new formulation of subcutaneous (s.c.) interferon-beta-1a has been developed (Rebif (R) New Formulation, RNF), produced without fetal bovine serum and without human serum albumin as an excipient, with the aim of improving injection tolerability, and reducing immunogenicity. Objectives This article reports 96-week analyses of a Phase IIIb, open-label study of the safety and immunogenicity of RNF compared with historical (EVIDENCE study) and recent (REGARD study) data on the original formulation. Methods Patients with relapsing multiple sclerosis (McDonald criteria) and an Expanded Disability Status Scale score < 6.0 received RNF, 44 mu g s.c. three times weekly. Results The proportion of neutralizing antibody-positive (NAb+) patients (serum NAb status >= 20 neutralizing units/mL) at week 96 (last observation carried forward; primary endpoint) was 17.4% (exact 95% confidence interval [CI]: 13.0-22.5), compared with 21.4% (95% CI: 17.2-26.2) in the EVIDENCE study, and 27.3% ( 95% CI: 22.8-32.1) in the REGARD study. The proportion of patients NAb+ at any time during the 96 weeks was 18.9% (95% CI: 14.4-24.2), compared with 27.1% (95% CI: 22.4-32.2) and 33.7% (95% CI: 28.9-38.7), respectively. Most pre-specified categories of adverse events were reported by patients in the RNF study at a similar or lower proportion than in the EVIDENCE and REGARD studies. Injection-site reactions were experienced by fewer patients than in the EVIDENCE and REGARD studies. Conclusions RNF has improved overall immunogenicity and safety profiles compared with the original formulation. Multiple Sclerosis 2009; 15: 219-228. http://msj.sagepub.com