By Maria Bishop
BOSTON, MA -- May 8, 2007 -- One-year results of a phase 3b trial of the new formulation interferon beta-1a (Rebif New Formulation; RNF) demonstrate an improved safety and immunogenicity profile at a high dose and high frequency in patients with relapsing multiple sclerosis (MS), according to research presented here at the American Academy of Neurology (AAN) 59th Annual Meeting.
Treatment with interferon beta in MS patients can be associated with the development of neutralizing antibodies (NAbs), which have been shown to reduce the therapeutic effect of interferon at high titers, said lead investigator James P. Simsarian, MD, director, Multiple Sclerosis Program, Neurology Center of Fairfax, Ltd., Fairfax, Virginia, and neurologist, Inova Fairfax Hospital, Falls Church, Virginia.
The new human serum albumin-free formulation of Rebif was created to minimize the incidence of NAbs and to optimize the potential benefits of treatment with interferon.
A 96-week multicenter, single-arm, open-label study of RNF enrolled 260 adults with an Expanded Disability Status Scale score < 6.0 and a diagnosis of relapsing MS according to the McDonald criteria. Patients in the study self-injected RNF 44 mcg/0.5 mL subcutaneously, 3 times weekly.
Blood samples were examined at weeks 12, 24, and 48, and the proportion of RNF-treated Nab-positive patients was compared with historical Rebif data from similar patients treated with 44 mcg Rebif, 3 times weekly in the Evidence of Interferon Dose-response: European North American Comparative Efficacy (EVIDENCE) study.
At 48 weeks, 227 (87.3%) of patients were still on treatment. Patients treated with RNF were nearly 6 times less likely to become Nab-positive (titer >/= 20 NU/mL) at both 24 weeks and 48 weeks compared with patients in the EVIDENCE study.
Incidence of prespecified adverse events was markedly lower for injection-site reaction in RNF (30%) versus historical data (84%), which represented a threefold reduction. Similar reductions were noted for cytopenia (10% vs 12%), depression and suicidal ideation (6% vs 20%), hepatic disorders (13% vs 17%), skin rashes (5% vs 12%), thyroid disorders (2% vs 5%), and hypersensitivity reactions (5% vs 3%).
According to the authors, these changes constitute notable improvements to the typical safety profile of injectable Rebif.
As expected with an HSA-free formulation, incidence of flu-like symptoms was higher with RNF (71% vs 48%), although most events were mild/moderate in severity.
This study was sponsored by Merck Serono International SA.
[Presentation titles: Safety and Immunogenicity of Rebif New Formulation (RNF) a New Subcutaneous Formulation of Interferon beta-1a 44 mcg Three Times Weekly: 1-Year Results of a Phase IIIb Study in Patients With Relapsing Multiple Sclerosis. Abstract P06.077. Safety and Immunogenicity of Rebif New Formulation (RNF) a New Subcutaneous Formulation of Interferon beta-1a 44 mcg Three Times Weekly: 1-Year Results of a Phase IIIb Study in Patients With Relapsing Multiple Sclerosis. Abstract P06.077]
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