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Comparing biosimilar SB2 with reference infliximab after 54 weeks of a double-blind trial: clinical, structural and safety results.

ABSTRACT: SB2 is a biosimilar to the reference infliximab (INF). Similar efficacy, safety and immunogenicity between SB2 and INF up to 30 weeks were previously reported. This report investigates such clinical similarity up to 54 weeks, including structural joint damage.In this phase III, double-blind, parallel-group, multicentre study, patients with moderate to severe RA despite MTX were randomized (1:1) to receive 3 mg/kg of either SB2 or INF at 0, 2, 6 and every 8 weeks thereafter. Dose escalation by 1.5 mg/kg up to a maximum dose of 7.5 mg/kg was allowed after week 30. Efficacy, safety and immunogenicity were measured at each visit up to week 54. Radiographic damage evaluated by modified total Sharp score was measured at baseline and week 54.A total of 584 patients were randomized to receive SB2 (n = 291) or INF (n = 293). The rate of radiographic progression was comparable between SB2 and INF (mean modified total Sharp score difference: SB2, 0.38; INF, 0.37) at 1 year. ACR responses, 28-joint DAS, Clinical Disease Activity Index and Simplified Disease Activity Index were comparable between SB2 and INF up to week 54. The incidence of treatment-emergent adverse events and anti-drug antibodies were comparable between treatment groups. Such comparable trends of efficacy, safety and immunogenicity were consistent from baseline up to 54 weeks. The pattern of dose increment was also comparable between SB2 and INF.SB2 maintained similar efficacy, safety and immunogenicity with INF up to 54 weeks in patients with moderate to severe RA. Radiographic progression was comparable at 1 year.ClinicalTrials.gov (http://clinicaltrials.gov; NCT01936181) and EudraCT (https://www.clinicaltrialsregister.eu; 2012-005733-37).

SUBMITTER: Smolen JS

PROVIDER: S-EPMC5850768 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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Comparing biosimilar SB2 with reference infliximab after 54 weeks of a double-blind trial: clinical, structural and safety results.

Smolen Josef S JS Choe Jung-Yoon JY Prodanovic Nenad N Niebrzydowski Jaroslaw J Staykov Ivan I Dokoupilova Eva E Baranauskaite Asta A Yatsyshyn Roman R Mekic Mevludin M Porawska Wieskawa W Ciferska Hana H Jedrychowicz-Rosiak Krystyna K Zielinska Agnieszka A Choi Jasmine J Rho Young Hee YH

Rheumatology (Oxford, England) 20171001 10

<h4>Objectives</h4>SB2 is a biosimilar to the reference infliximab (INF). Similar efficacy, safety and immunogenicity between SB2 and INF up to 30 weeks were previously reported. This report investigates such clinical similarity up to 54 weeks, including structural joint damage.<h4>Methods</h4>In this phase III, double-blind, parallel-group, multicentre study, patients with moderate to severe RA despite MTX were randomized (1:1) to receive 3 mg/kg of either SB2 or INF at 0, 2, 6 and every 8 week ...[more]

PMID: 28957563

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Project description:BACKGROUND:BCD-022 is a trastuzumab biosimilar which was shown to be equivalent to reference trastuzumab in a wide panel of physicochemical studies as well as preclinical studies in vitro and in vivo. International multicenter phase III clinical trial was conducted to comparatively assess efficacy and safety of BCD-022 and reference trastuzumab in combination with paclitaxel used as the therapy of metastatic HER2(+) breast cancer. Pharmacokinetics and immunogenicity were also studied. METHODS:Patients with no previous treatment for metastatic HER2(+) breast cancer were randomly assigned 1:1 to BCD-022 or reference trastuzumab and were treated with trastuzumab + paclitaxel. Therapy continued for 6?cycles of therapy (every 3?weeks), until progression of the disease or unbearable toxicity. Primary study endpoint was overall response rate. Study goal was to prove equivalent efficacy of BCD-022 and reference trastuzumab. Equivalence margins for 95% CI for difference in overall response rates were set at [-?20%; 20%]. RESULTS:In total 225 patients were enrolled into the study, 115 in BCD-022 arm and 110 in reference trastuzumab arm. Overall response rate was 49.6% in BCD-022 arm and 43.6% in reference trastuzumab arm. Limits of 95% CI for difference of overall response rates between arms were [(-?8.05)-19.89%], thus, they lied within predetermined equivalence margins [-?20%; 20%]. Profile of adverse events was similar between groups (any AEs were reported in 93.81% of patients in BCD-022 arm and 94.55% of patients in reference arm). No unexpected adverse reactions were reported throughout the study. No statistically significant differences regarding antibody occurrence rate (either BAb or NAb) was found between BCD-022 (n?=?3; 2.65%) and comparator (n?=?4; 3.64%). Both drug products are characterized with low occurrence rate and short life of anti-trastuzumab antibodies. Pharmacokinetics assessment after 1st and 6th study drug injection also demonstrated equivalent PK parameters by all outcome measures: AUC0-504, ?m??, ?max, T1/2. Analysis of Ctrough did not reveal any significant inter-group differences as well. CONCLUSIONS:Thus, results of this study have demonstrated therapeutic equivalence of trastuzumab biosimilar BCD-022 and referent trastuzumab drug. TRIAL REGISTRATION:The trial was registered with ClinicalTrials.gov (Study Number NCT01764022 ). The date of registration was January 9, 2013.

Project description:Background:Following the functional and physicochemical characterization of a proposed biosimilar, comparative clinical studies help to confirm biosimilarity by demonstrating similar safety and efficacy to the reference product in a sensitive patient population. Patients and methods:LA-EP2006 is a proposed biosimilar that has been developed for pegfilgrastim, a long-acting form of granulocyte colony-stimulating factor for the prevention of neutropenia. The current analysis reports data pooled from two independent, multinational, prospective, randomized, controlled, double-blind phase III studies of similar design comparing the safety and efficacy of reference pegfilgrastim with LA-EP2006 in patients with breast cancer receiving myelotoxic (neo)adjuvant TAC (docetaxel, doxorubicin, and cyclophosphamide) chemotherapy and requiring granulocyte colony-stimulating factor. Results:A total of 624 patients were randomized in the PROTECT-1 and PROTECT-2 studies (NCT01735175; NCT01516736) (LA-EP2006: n?=?314; reference: n?=?310). Baseline characteristics of patients were well balanced across treatment groups. The primary end point, mean duration of severe neutropenia in the first chemotherapy cycle was similar in both the LA-EP2006 and reference groups (1.05?±?1.055 days versus 1.01?±?0.958 days), with a treatment difference of?-?0.04 days [95% confidence interval (CI): -0.19 to 0.11] that met the equivalence criteria (the 95% CI were within the defined margin of?±1?day). Secondary end points, such as the nadir of absolute neutrophil count and the incidence of febrile neutropenia, were also similar between LA-EP2006 and reference pegfilgrastim. The safety and tolerability profile of LA-EP2006 was similar to that observed with reference pegfilgrastim, and there were no reports of neutralizing antibodies. Conclusions:This pooled analysis confirms, as a part of totality of evidence approach, that the proposed biosimilar pegfilgrastim LA-EP2006 has a comparable efficacy and safety profile to reference pegfilgrastim in patients with breast cancer receiving TAC chemotherapy. Clinical trial numbers:NCT01735175 and NCT01516736.

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Comparing biosimilar SB2 with reference infliximab after 54 weeks of a double-blind trial: clinical, structural and safety results.

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Comparing biosimilar SB2 with reference infliximab after 54 weeks of a double-blind trial: clinical, structural and safety results.

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