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-β-1a has been developed (Rebif® 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 μg 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.