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:

MATRIX (Measuring neutralizing Antibodies in patients TReated with Interferon beta-1a IM in MeXico) was primarily a cross-sectional phase 4 study of patients with relapsing multiple sclerosis (RMS) that evaluated neutralizing antibody (NAb) frequency in Mexican and Colombian patients treated with intramuscular interferon (IFN) beta-1a in the form of Avonex^® or the biosimilar drug Jumtab^®. A secondary long-term retrospective observational evaluation of safety, tolerability, and relapses was also performed for patients in each arm of the study. In the cross-sectional portion of the study, patients with multiple sclerosis who had been treated with once-weekly Avonex (n=36) or Jumtab (n=29) self-injections as their first and only disease-modifying therapy for 1–3 years were retrospectively identified. The primary and secondary endpoints were proportion of patients with NAb levels >100 tenfold reduction units (TRU) and >20 TRU. The biological response to IFN beta-1a injections was assessed by change in serum neopterin levels and by pre- versus post-dose concentration difference. Safety, tolerability, and relapse-related information were also retrospectively assessed. No patients developed NAb levels >100 TRU. Neopterin levels were significantly higher relative to baseline with Avonex than with Jumtab. Supporting this result, flu-like symptoms were reported in a greater proportion of Avonex-treated than Jumtab-treated patients. No unexpected adverse events or significant differences in relapses were observed. In conclusion, Avonex and Jumtab exhibited minimal immunogenicity; Jumtab was associated with significantly lower neopterin activation and flu-like symptom frequency compared with Avonex, suggesting less IFN bioactivity with Jumtab.

Keywords::

• multiple sclerosis
• neutralizing antibodies
• flu-like symptoms
• neopterin
• follow-on biologics
• biosimilars

Acknowledgments

Biogen provided funding for editorial support in the development of this paper. Kristine Zerkowski and Anne Williamson of Infusion Communications wrote the first draft of the manuscript based on input from authors, and Joshua Safran of Infusion Communications copyedited and styled the manuscript per journal requirements. Biogen participated in the design of the study; in the collection, analysis, and interpretation of data; in the writing of the report; and in the decision to submit the article for publication. The MATRIX Investigator Group includes the following individuals: Carlos Cuevas (Instituto Mexicano del Seguro Social, Mexico City, Mexico), Francisco Flores-Ramírez (Hospital Regional ISSSTE Monterrey, Monterrey, Mexico), Miguel Macías-Islas (Universidad de Guadalajara, Guadalajara, Mexico), Sergio Sauri-Suárez (Centro Medico Nacional 20 de Noviembre, Mexico City, Mexico), Jose Manuel Aleman Pedroza (Universidad Autónoma de Guadalajara, Guadalajara, Mexico), Eduardo Duriez Sotelo (Universidad de Monterrey, Monterrey, Mexico), Maria de la Luz Villalpando Gueich (Hospital Angeles Leon, Leon, Mexico), Raul Arcega Revilla (Clinica Neurologica, Puebla, Mexico), Leonardo Llamas Lopez (Hospital Regional ISSSTE Dr Valentín Gómez Farías, Guadalajara, Mexico), Ernesto Ojeda (Universidad del Rosario, Bogota, Colombia), and Pablo Lopez (Neurologos Clinicos Asociados Cia., Ltda, Bogota, Colombia). The authors had full editorial control of the paper and provided their final approval of all content. These results were presented in part at the 28th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (abstract published in Multiple Sclerosis Journal: http://msj.sagepub.com/content/18/4_suppl.toc) and the 11th International Congress of Neuroimmunology (abstract published in Journal of Neuroimmunology: http://www.jni-journal.com/article/S0165-5728(12)00304-9/abstract) as poster presentations. The actual paper, however, has never been published.

Disclosure

This work was supported by Biogen (study number MEX-AVX-12-10324). Carlos Cuevas, Francisco Flores-Ramírez, Miguel Macías-Islas, and Sergio Sauri-Suárez have nothing to disclose. Florian Deisenhammer has participated in meetings sponsored by or received honoraria for acting as an advisor/speaker for Bayer Healthcare, Biogen, Genzyme-Sanofi, Merck, Novartis Pharma, and Teva-Ratiopharm; his institution has received financial support for participation in randomized controlled trials from Bayer Schering Pharma, Biogen, Merck Serono, and Teva Pharmaceuticals. Xiaojun You and Bjørn Sperling are employees of Biogen. Mariano Scolnik and Regine Buffels were employees of Biogen at the time of this analysis. The authors report no other conflicts of interest in this work.