A multicenter, open-label, phase II study of the immunogenicity and safety of a new prefilled syringe (liquid) formulation of avonex in patients with multiple sclerosis

• Published in: Clinical therapeutics Vol. 26; no. 4; pp. 511 - 521
• Main Authors: Phillips, J.Theodore, Rice, George, Frohman, Elliot, Vande Gaer, Luc, Scott, Thomas, Haas, Judith, Eggenberger, Eric, Freedman, Mark S, Stuart, William, Cunha, Luis, Jacobs, Lawrence, Oger, Joel, Arnold, Douglas, Jock Murray, T, DiBiase, Mary, Jethwa, Vijay, Goelz, Susan
• Format: Journal Article
• Language: English
• Published: Belle Mead, NJ EM Inc USA 01.04.2004; Excerpta Medica; Elsevier Limited
• Subjects: Adjuvants, Immunologic - administration & dosage; Adjuvants, Immunologic - therapeutic use; Adult; Antibodies; Bioavailability; Biological and medical sciences; Collaboration; Cytokines; Disposable Equipment; Drug dosages; Enzyme-Linked Immunosorbent Assay; Female; Humans; immunogenicity; Injections, Intramuscular; Interferon; Interferon beta-1a; Interferon-beta - administration & dosage; Interferon-beta - immunology; Interferon-beta - therapeutic use; liquid Avonex; Male; Medical sciences; Middle Aged; Multiple sclerosis; Multiple Sclerosis, Relapsing-Remitting - drug therapy; Multiple Sclerosis, Relapsing-Remitting - immunology; Neurology; neutralizing antibodies; Pharmacology. Drug treatments; prefilled syringe; Syringes; Canada; Atlanta Georgia; Montreal Quebec Canada; United States > US; Texas; Michigan; interferon beta-1a; liquid Avonex; neutralizing antibodies; prefilled syringe; multiple sclerosis; immunogenicity; Human; Nervous system diseases; Multiple sclerosis; Toxicity; Cytokine; Inflammatory disease; Immunogenicity; Formulation; Central nervous system disease; Phase II trial; Interferon; interferon beta-la
• ISSN: 0149-2918; 1879-114X
• DOI: 10.1016/S0149-2918(04)90053-7

Background: A new liquid formulation of Avonex (interferon beta-1a [IFNβ-1a]) in a prefilled syringe has been developed to make administration of the drug easier for patients with multiple sclerosis (MS). This formulation does not contain human serum albumin (HSA), often added to interferon (IFN) products for stabilization. However, formulation changes may alter the secondary, tertiary, and quaternary structures of IFNβ products. These kinds of structural changes could lead to the formation of antibodies directed against IFNβ. Some of these anti-IFN antibodies may neutralize the biologic activity of IFNβ. Objective: This study was designed to determine the immunogenicity and safety of the new prefilled syringe (liquid) HSA-free formulation of Avonex in patients with relapsing MS. Methods: This was a multicenter, single-arm, open-label study. Patients with relapsing MS received liquid, HSA-free Avonex 30 μg by IM injection from a prefilled syringe once weekly for up to 24 months. Immunogenicity and safety were assessed every 3 months. Serum levels of neutralizing antibodies (NAbs) were measured at baseline and every 3 months using a 2-step enzyme-linked immunosorbent assay and antiviral cytopathic effect assay. Results: A total of 153 patients (121 women, 32 men; mean [SD] age, 39.6 [9.9] years; age range, 19.0–59.0 years) were enrolled in the study. Sera were available for analysis from 125 and 119 patients after 18 and 24 months of treatment, respectively. By 18 months, 1 patient (1%) had ≥2 consecutive titers of ≥20, a level at which the persistent presence of NAbs has been shown in some studies to have clinical consequences. By 24 months, 1 additional patient (total 2%) had ≥2 consecutive titers of ≥20. At 18 months, 5 patients (4%) had ≥1 NAb titer of ≥5; at 24 months, 6 patients (5%) had ≥1 NAb titer of ≥5. The safety profile of liquid Avonex was comparable to the lyophilized form containing HSA. Conclusions: The prefilled syringe (liquid) HSA-free formulation of Avonex was well tolerated and showed a low level of immunogenicity. Over 24 months, 2% of patients developed persistent NAbs (≥2 consecutive titers of ≥20).