Extension Study of PF‐05280586, a Potential Rituximab Biosimilar, Versus Rituximab in Subjects With Active Rheumatoid Arthritis

Abstract

ObjectiveThis extension study provided continued treatment to subjects with active rheumatoid arthritis who had participated for ≥16 weeks in a pharmacokinetic similarity study of PF‐05280586 (potential rituximab biosimilar). Objectives were to evaluate overall pharmacokinetics, pharmacodynamics, immunogenicity, safety, and tolerability of PF‐05280586 after transition from rituximab reference products to PF‐05280586, and follow‐up of biomarker and efficacy assessments.MethodsSubjects were offered ≤3 additional courses of treatment of PF‐05280586, with or without a single transition from rituximab in Europe (rituximab‐EU; MabThera) or the US (rituximab‐US; Rituxan) to PF‐05280586. Each course comprised 2 intravenous infusions (1,000 mg on days 1 and 15, separated by 24 weeks [± 8 weeks]).ResultsOf 220 subjects in the parent study, 185 were randomized and included in this study. There were no notable differences in drug concentrations between groups or across courses, with little variation in depletion of CD19+ B cells between groups, and no apparent relationship between infusion‐related reactions and antidrug antibodies with or without single transition from rituximab reference products to PF‐05280586. Long‐term safety and tolerability of PF‐05280586 was acceptable in all groups for up to 96 weeks, with a low incidence of treatment‐emergent adverse events independent of single drug transition. The percentage of subjects with a low disease activity score and disease activity score remission was similar across groups for all time points, and responses were sustained until end of study.ConclusionThis study demonstrated acceptable safety, tolerability, and immunogenicity, with or without single transition from rituximab reference products to PF‐05280586, without increased immunogenicity on single transition.

The Efficacy, Safety, and Immunogenicity of Switching Between Reference Biopharmaceuticals and Biosimilars: A Systematic Review

“…Five studies were conducted in the scope of the clinical biosimilar development (i.e., the single partial crossover switch to BCD-020 62 ; a Russian product, not approved in the EU or the United States, thus not to be considered a true biosimilar evaluated by a stringent regulatory framework), an open-label extension phase I study for CT-P10, 63 an open-label extension phase III study for CT-P10, 64 a double-blind RCT for GP2013, 65 and a randomized extension phase I study for PF-05280586. 66 All studies were performed in patients with RA. None of these studies detected safety, efficacy, or immunogenicity issues related to switching.…”

Long-term efficacy, safety and immunogenicity in patients with rheumatoid arthritis continuing on an etanercept biosimilar (LBEC0101) or switching from reference etanercept to LBEC0101: an open-label extension of a phase III multicentre, randomised, double-blind, parallel-group study

“…Several studies have documented continued efficacy and safety after switching from RPs to biosimilars, and after long-term treatment [18–21]. In a study by Emery et al [18], patients received the ETN biosimilar SB4 for 48 weeks in an open-label extension after an initial 52-week randomised controlled trial of SB4 or ETN.…”

“…While establishing the efficacy and safety of long-term use of biosimilars or that of switching from reference product (RP) to biosimilars is not mandatory for regulatory processes, it is very important to examine these parameters in clinical settings for prescribing doctors and patients. Indeed, clinical trials of several biosimilars have shown promising results in terms of long-term efficacy and safety, confirming their potential as an alternative to branded products in patients with RA [16–21].…”

Prospects for Anti-B-Cell Therapy in Immuno-Inflammatory Rheumatic Diseases

“…Снижение стоимости лечения дорогостоящими ГИБП и, как следствие, увеличение доступности инновационной терапии у пациентов, живущих в странах с ограниченными экономическими ресурсами, является при- оритетной задачей здравоохранения всех стран мира. Эта проблема частично решена благодаря разработке биоаналогов (biosimilars) ГИБП, широкое применение которых в клинической практике стало возможным благодаря окончанию срока действия патентов для многих оригинальных ГИБП [335][336][337][338][339], включая РТМ [340][341][342][343] В 2001 г. в России была основана биотехнологическая компания «БИОКАД», занимающаяся производством биоаналогов и оригинальных ГИБП. В настоящее время на разных стадиях разработки находятся ряд ГИБП, предназначенных для лечения аутоиммунных заболеваний, включая РТМ [344] Хотя бы одна НЛР / серьезная НЛР (СНЛР) была зарегистрирована у 48 (44,9%) пациентов в группе Ацеллбия ® + МТ и у 22 (43,1%) в группе ПЛ + МТ (р=0,974).…”