Dataset Information

A Randomized, Double-Blind, Efficacy and Safety Study of PF-05280586 (a Rituximab Biosimilar) Compared with Rituximab Reference Product (MabThera®) in Subjects with Previously Untreated CD20-Positive, Low-Tumor-Burden Follicular Lymphoma (LTB-FL).

ABSTRACT: BACKGROUND:Biosimilars are highly similar to the licensed biologic ("reference product"), with no clinically meaningful differences in safety, purity, or potency between the two products. OBJECTIVE:This comparative 52-week clinical study evaluated the efficacy, safety, immunogenicity, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-05280586 (Ruxience™ [a rituximab biosimilar]) versus rituximab reference product sourced from the EU (MabThera®; rituximab-EU). PATIENTS AND METHODS:Subjects with CD20-positive, low-tumor-burden follicular lymphoma (LTB-FL) and an Eastern Cooperative Oncology Group performance status 0-1 were randomized (1:1) to PF-05280586 or rituximab-EU (375 mg/m2 intravenously [once weekly for 4 weeks at days 1, 8, 15, and 22]), stratified using the Follicular Lymphoma International Prognostic Index 2 classification. The primary endpoint was overall response rate (ORR) at week 26 (percentage of subjects achieving complete response [CR] or partial response [PR]). Therapeutic equivalence was concluded if the two-sided 95% confidence interval (CI) for the difference in ORR between groups was within the prespecified margin (±?16%). Secondary endpoints included progression-free survival (PFS), CR rate, safety, immunogenicity, PK, and PD. RESULTS:A total of 394 subjects were randomized: PF-05280586 (n?=?196) or rituximab-EU (n?=?198). ORR at week 26 was 75.5% (PF-05280586) versus 70.7% (rituximab-EU), for a difference of 4.66%; 95% CI (-?4.16 to 13.47), which was entirely within the prespecified equivalence margin. Rates of CR were 29.3% (PF-05280586) versus 31.0% (rituximab-EU). Estimated 1-year PFS rates were 78.2% (95% CI 70.2-84.2) and 83.0% (95% CI 75.0-88.6) for PF-05280586 and rituximab-EU, respectively. Safety, immunogenicity, and mean serum concentrations were similar between groups. CONCLUSIONS:The efficacy, safety, immunogenicity, PK, and PD of PF-05280586 and rituximab-EU were similar up to week 52 in subjects with previously untreated CD20-positive LTB-FL. CLINICAL TRIAL REGISTRATION:ClinicalTrials.gov, NCT02213263 and EudraCT (2014-000132-41).

SUBMITTER: Sharman JP

PROVIDER: S-EPMC7113218 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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Publications

A Randomized, Double-Blind, Efficacy and Safety Study of PF-05280586 (a Rituximab Biosimilar) Compared with Rituximab Reference Product (MabThera<sup>®</sup>) in Subjects with Previously Untreated CD20-Positive, Low-Tumor-Burden Follicular Lymphoma (LTB-FL).

Sharman Jeff P JP Liberati Anna Marina AM Ishizawa Kenichi K Khan Tahira T Robbins Jeffery J Alcasid Ann A Rosenberg Julie Ann JA Aurer Igor I

BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy 20200401 2

<h4>Background</h4>Biosimilars are highly similar to the licensed biologic ("reference product"), with no clinically meaningful differences in safety, purity, or potency between the two products.<h4>Objective</h4>This comparative 52-week clinical study evaluated the efficacy, safety, immunogenicity, pharmacokinetics (PK), and pharmacodynamics (PD) of PF-05280586 (Ruxience™ [a rituximab biosimilar]) versus rituximab reference product sourced from the EU (MabThera<sup>®</sup>; rituximab-EU).<h4>Pa ...[more]

PMID: 31820339

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Project description:Development of bio-therapeutics has exhibited exponential growth in China over the past decade. However, no biosimilar drug has been approved in China (CN) due to the lack of a national biosimilar regulatory guidance. HLX01, a rituximab biosimilar developed in China under European Medicines Agency biosimilar guidelines and requirements, was the first such drug submitted for regulatory review in China, and it is expected to receive approval there as a biosimilar product. To demonstrate the analytical similarities of HLX01, CN-rituximab (sourced in China but manufactured in Europe) and EU-rituximab (sourced and manufactured in Europe), an extensive 3-way physicochemical and functional similarity assessment using a series of orthogonal and state-of-the-art techniques was conducted, following the similarity requirement guidelines recently published by China's Center for Drug Evaluation. The results of the similarity study showed an identical protein amino acid sequence and highly similar primary structures between HLX01 and the reference product (RP) MabThera®, along with high similarities in higher order structures, potency, integrity, purity and impurity profiles, biological and immunological binding functions, as well as degradation behaviors under stress conditions. In addition, HLX01 presented slightly lower aggregates and better photostability compared with the RP. Despite slight changes in relative abundance of glycan moieties and heavy chain C-terminal lysine modification, no differences in biological activities and immunological properties were observed between the RP and HLX01. In conclusion, HLX01 is highly similar to CN- and EU-sourced RP in terms of physicochemical properties and biological activities, suggesting similar product quality, efﬁcacy, and safety. The regulatory requirements interpreted and applied towards the HLX01 marketing application sets a precedent for analytical similarity assessment of biosimilar products in China.

Project description:ObjectiveThis multi-center, open-label, randomized, parallel-controlled phase II study aimed to compare the pharmacokinetics (PK), pharmacodynamics (PD) and safety profile of ripertamab (SCT400), a recombinant anti-CD20 monoclonal antibody, to rituximab (MabThera®) in patients with CD20-positive B-cell non-Hodgkin lymphoma (NHL).MethodsPatients with CD20-positive B-cell NHL who achieved complete remission or unconfirmed complete remission after standard treatment were randomly assigned at a 1:1 ratio to receive a single dose of ripertamab (375 mg/m2) or rituximab (MabThera®, 375 mg/m2). PK was evaluated using area under the concentration-time curve (AUC) from time 0 to d 85 (AUC0-85 d), AUC from time 0 to week 1 (AUC0-1 w), AUC from time 0 to week 2 (AUC0-2 w), AUC from time 0 to week 3 (AUC0-3 w), AUC from time 0 to week 8 (AUC0-8 w), maximum serum concentration (Cmax), terminal half-life (T1/2), time to maximum serum concentration (Tmax) and clearance (CL). Bioequivalence was confirmed if the 90% confidence interval (90% CI) of the geometric mean ratio of ripertamab/rituximab was within the pre-defined bioequivalence range of 80.0%-125.0%. PD, immunogenicity, and safety were also evaluated.ResultsFrom December 30, 2014 to November 24, 2015, a total of 84 patients were randomized (ripertamab, n=42; rituximab, n=42) and the PK analysis was performed on 76 patients (ripertamab, n=38; rituximab, n=38). The geometric mean ratios of ripertamab/rituximab for AUC0-85 d, AUC0-inf, and Cmax were 96.1% (90% CI: 87.6%-105.5%), 95.9% (90% CI: 86.5%-106.4%) and 97.4% (90% CI: 91.6%-103.6%), respectively. All PK parameters met the pre-defined bioequivalence range of 80.0%-125.0%. For PD and safety evaluation, there was no statistical difference in peripheral CD19-positive B-cell counts and CD20-positive B-cell counts at each visit, and no difference in the incidence of anti-drug antibodies was observed between the two groups. The incidences of treatment-emergent adverse events and treatment-related adverse events were also comparable between the two groups.ConclusionsIn this study, the PK, PD, immunogenicity, and safety profile of ripertamab (SCT400) were similar to rituximab (MabThera®) in Chinese patients with CD20-positive B-cell NHL.

Dataset Information

A Randomized, Double-Blind, Efficacy and Safety Study of PF-05280586 (a Rituximab Biosimilar) Compared with Rituximab Reference Product (MabThera®) in Subjects with Previously Untreated CD20-Positive, Low-Tumor-Burden Follicular Lymphoma (LTB-FL).

Publications

A Randomized, Double-Blind, Efficacy and Safety Study of PF-05280586 (a Rituximab Biosimilar) Compared with Rituximab Reference Product (MabThera<sup>®</sup>) in Subjects with Previously Untreated CD20-Positive, Low-Tumor-Burden Follicular Lymphoma (LTB-FL).

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