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
Author(s)
James Simsarian, MD, Neurologist1, Ahmad AL-Sabbagh, MD, Vice President Medical Affairs, Neurology, US2, Randy Bennett, BA, Director, Medical Affairs2, Bettina Stubinski, MD, Medical Director3, Gabriel Pardo, MD, Medical Director41Neurology Center of Fairfax, Fairfax, VA, USA; 2 Serono, Inc, Rockland, MA, USA; 3 Serono, Inc, Geneva, Switzerland; 4 Multiple Sclerosis Center of Oklahoma, Oklahoma City, OK, USA
OBJECTIVES: To compare the safety and immunogenicity of a new human serum albumin (HSA)-free formulation of interferon (IFN) beta-1a (Rebif New Formulation; RNF) with historical Rebif data. RNF was developed through an extensive research program to maximize treatment benefit and patient outcomes by improving injection tolerability and reducing neutralizing antibodies (NAbs). METHODS: This 48-week analysis of a 96-week phase IIIb multicenter single-arm open-label study (25632) compared RNF (44mcg/0.5mL, self-injected subcutaneously three-times weekly [tiw]) with historical Rebif® 44mcg tiw data (EVIDENCE study) in patients with relapsing multiple sclerosis (18–60 years; EDSS<6.0). Safety analyses included eight pre-specified adverse event (AE) groups of interest, including injection-site reactions (ISR) and flu-like symptoms (FLS; includes ‘influenza-like illness' or =2 other FLS terms within 48-hours). NAb titers =20NU/mL at last assessment up to week 48 were considered NAb+; ‘persistent NAbs' was defined as NAb+ at 24 and 48 weeks. RESULTS: At week 48, 227/260 patients (87.3%) remained on treatment. Compared with historical data, incidence of pre-specified AEs in the RNF study was markedly lower for ISR (29.6% versus 83.8%; a three-fold reduction), and similar or lower for cytopenia (9.6% versus 11.8%), depression and suicidal ideation (5.8% versus 19.8%), hepatic disorders (13.1% versus 16.8%), skin rashes (5.4% versus 12.1%), thyroid disorders (2.3% versus 5.0%) and hypersensitivity reactions (5.4% versus 3.2%). As expected with an HSA-free formulation, incidence of FLS was higher with RNF (70.8% versus 48.1%) and most events were mild/moderate in severity. Compared with historical data, a markedly smaller proportion of RNF patients had persistent NAbs (2.5% [95%CI: 1.0–5.4] versus 14.3% [95%CI: 10.7–18.6]) or NAbs at week 48 (13.9% [95%CI: 9.9–18.7] versus 24.4% [95%CI: 19.9–29.4]). 50% of NAb+ titers were low (below 200NU/mL). CONCLUSION: These data suggest that RNF has better overall safety and lower immunogenic potential than Rebif®.
Conference/Value in Health Info
2007-05, ISPOR 2007, Arlington, VA, USA
Value in Health, Vol. 10, No.3 (May/June 2007)
Code
PND2
Topic
Epidemiology & Public Health
Topic Subcategory
Safety & Pharmacoepidemiology
Disease
Multiple Diseases, Neurological Disorders