Low immunogenicity but reduced bioavailability of an interferon beta-1a biosimilar compared with its biological parent: results of MATRIX, a cross-sectional, multicenter phase 4 study

Abstract

Objective: Neutralizing antibody (NAb) formation reduces the clinical activity and efficacy of interferon beta (IFN(beta)) therapies. Avonex(registered trademark) (Biogen Idec, Weston, MA, United States), an intramuscular (IM) IFN(beta)-1a formulation, has low immunogenicity, affecting 2%-5% of patients, while the immunogenicity of the biosimilar drug Jumtab(registered trademark) (Probiomed, Miguel Hidalgo, Mexico) has not been reported. The primary objective of the present study was to compare the NAb frequency in multiple sclerosis (MS) patients treated weekly with either Avonex or Jumtab. Methods: MATRIX was a retrospective, cross-sectional phase 4 study conducted in Mexico and Colombia to determine NAb levels in MS patients with no prior disease-modifying therapy exposure who were treated with either Avonex or Jumtab (expected enrollment of n= 90 per drug) for 1-3 years prior to study enrollment. NAb levels >100 IU as measured with a luciferase assay were considered positive. Neopterin induction, a pharmacodynamic measure of IFN response, was taken as the change in serum levels from pre-dose to 48 h post-dose. Possible relationships between patient NAb status and drug tolerability/safety were also evaluated. Data are presented as the mean(plus or minus)standard deviation. Results: Study enrollment was limited due to pharmacy substitution of branded medications with locally produced biosimilars and a lack of availability of study medications in local pharmacy markets. The Avonex (n=36) and Jumtab (n=29) groups differed in age (37.1 vs 44.6 years; P<0.01); there were no other significant baseline differences. The mean duration of IFN(beta)-1a therapy was 24.5(plus or minus) 7.5 months for Avonex and 22.1(plus or minus)8.1 months for Jumtab. No patients developed NAb levels >100 IU during the study period. Avonex patients had higher levels of neopterin induction (2.4(plus or minus)2.2 ng/ml vs 0.7(plus or minus)1.2 ng/ml; P<0.01) and flu-like symptom (FLS) incidence (80.6% vs 31.0%) than Jumtab patients. The groups did not differ significantly in either relapse rate or incidence of unexpected adverse events. Conclusions: Both Avonex and Jumtab exhibited minimal immunoge-nicity. Neopterin activation and FLS were lower with Jumtab, suggesting that Jumtab has lower IFN activity than Avonex. These results underline the importance of performing a multimodal assessment to establish a biosimilar drug's immunogenicity, pharma-cokinetics, and pharmacodynamics. A prospective study with a larger sample size is needed to evaluate the relative safety and efficacy of these drugs. Supported by Biogen Idec Inc.