A Phase 1 study comparing subcutaneous and intramuscular routes of administration of peginterferon beta-1a: macrophage-producing neopterin levels as biomarker

Abstract

Abstract Background Developing effective therapies for patients can be difficult as many fail due to safety concerns. Changes in route of administration (ROA) for approved therapies offers options to patients while mitigating known side effects. Peginterferon beta-1a (PEG) is approved for subcutaneous (SC) administration at 125 mcg every 2 weeks for patients with relapsing forms of multiple sclerosis. Intramuscular (IM) administration is associated with a different safety profile from SC and could offer patients receiving PEG an additional treatment option. To confirm efficacy is maintained, neopterin – a reliable pharmacodynamic measure for IFN therapies that is produced by macrophages – was tested in a bioequivalence study. Methods A two-period, crossover study with healthy volunteers who received a single dose of PEG administered SC followed by a single dose administered IM (or vice versa) was conducted. Blood samples were collected up to 504 hours post dose to evaluate pharmacokinetic and pharmacodynamic measures, including neopterin. Results The study enrolled 136 participants. Serum neopterin concentrations following SC and IM administration were similar, with maximal concentrations (Epeak) reached at a median ETmax of 40.1 hours and 44.0 hours, respectively. Geometric mean neopterin levels increased from baseline to maximum concentration similarly between both routes, with an increase from 8.0 to 22.6 nmol/L for SC and from 8.1 to 23.2 nmol/L for IM. The overall exposure to neopterin was also similar between both routes. Conclusion These results demonstrate no major difference in PEG activity; therefore, PEG administered SC or IM is expected to have a comparable pharmacological impact on the body.