Biosimilar Monoclonal Antibodies Research Articles

HSD116 Real-World Utilization Patterns of Oncology Biosimilar Monoclonal Antibodies and Their Corresponding Reference Products

Multiple oncology biosimilar monoclonal antibodies (mAbs) are now available for use as therapeutic options with comparable safety/efficacy profiles to that of their reference biologics. The objective of this study was to describe real-world treatment pattens of rituximab-pvvr, trastuzumab-qyyp, and bevacizumab-bvzr and their associated reference biologics.

RWD71 Real-World Usage and Pattern of Biosimilar Monoclonal Antibodies of Trastuzumab, Rituximab and Bevacizumab in Oncology Practice in Japan

Oncology biosimilars hold the promise of reducing costs in Japan. Although the adoption of oncology biosimilars have been modest due to physicians’ perceptions and lack of operational guidance that supports usage to biosimilars, Japan showed an increase in the uptake of biosimilars.

Abstract 1734: Encapsulating therapeutic antibodies for tumor specific activation and delivery using a clinically validated pH-sensitive nanoparticle platform

Abstract Background: Though antibodies for cancer treatment have achieved clinical and commercial success over the past few decades, a large portion are limited by suboptimal efficacy and on-target off-tumor toxicity due to ubiquitous expression of their targets. A plethora of molecular engineering approaches have been introduced to restrict the activity of antibodies solely to tumor instead of healthy tissue with the goal of improving the therapeutic index, such as masking the binding sites of antibodies with inhibitory domains. However, sophisticated modification is usually required while the outcomes are often mediocre. Previously we developed an ultra-pH sensitive nanoparticle platform named ON-BOARD. The strength of this technology stems from its ability to preferentially release the payload specifically in the acidic tumor microenvironment while staying intact in normal tissue. The safety and feasibility of using such a platform have been demonstrated by successful delivery of fluorophore to tumors for imaging of multiple tumor types in Phase I and II clinical trials with Pegsitacianine (formerly “ONM-100”). Pegsitacianine has been shown to be generally well-tolerated with an infusion-related reaction as the most common adverse event in the clinical trials conducted to date. Based on the clinical results, we present the ON-BOARD platform herein as a potential universal and effective tool for tumor specific activation and delivery of therapeutic antibodies without the need for sophisticated antibody chemistry or engineering. Methods: Biosimilar monoclonal antibodies of atezolizumab, cetuximab, pembrolizumab, trastuzumab, and ipilimumab with the same variable region sequences as the original pharmaceutical drugs were used to demonstrate encapsulation by the ON-BOARD platform and pH-dependent activation. Encapsulated antibodies were purified using SEC and the encapsulation efficiencies were quantified by HPLC. Particle size and uniformity were studied by DLS. The formulations were accessed for bioactivity in vitro under neutral pH or acidified conditions using appropriate cell-based reporter assays. Results: ON-BOARD nanoparticles successfully encapsulated the antibodies mentioned above without additional modification of the original antibody. Encapsulation efficiency ranged from 50-100%. The formulations were characterized as uniformly distributed particles < 100nm in size with good stability. In vitro assessment by cell-based reporter assays demonstrated > 100-fold activation window between the acid-activated and intact formulations. The pH-dependent activation was further confirmed by affinity and binding assay. Conclusions: The ON-BOARD pH-sensitive nanoparticle platform demonstrated potential as an effective and universal tool for tumor specific activation and delivery of antibody-based therapeutics. Citation Format: Gaurav Bharadwaj, Qingtai Su, Stephen Gutowski, Curran Parpia, Ashley Campbell, Jason Miller, Tian Zhao. Encapsulating therapeutic antibodies for tumor specific activation and delivery using a clinically validated pH-sensitive nanoparticle platform [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1734.

Development of a flow cytometry-based potency assay for prediction of cytokine storms induced by biosimilar monoclonal antibodies

Cytokine release syndrome (CRS) is an undesired immune reaction that may cause dangerous side effects after the administration of novel biological therapies. In vitro cytokine release assays (CRA) are used for preclinical safety assessment prior to first-in-man dose administration of therapeutic monoclonal antibodies (mAbs). A variety of CRA platforms has been developed where the analysis of secreted cytokines is performed. Analysis of T cell activation markers is not performed routinely in CRA platforms and few studies have described intracellular cytokine levels after stimulation with therapeutic mAbs. In the present study, we performed a CRA using intracellular cytokine staining and assessment of extracellular T cell activation markers by flow cytometry. We used commercially available reference mAbs for the stimulation of peripheral blood mononuclear cells (PBMCs). We found that stimulation using solid phase (SP) dry coating with two different CD28 antibodies and muromonab-CD3 increased the percentage of IFN-ɣ + CD4+ and CD8+ T cells as well as of CD3-CD56+ NK cells compared to stimulation with antibodies in aqueous phase (AP). Expression of the T cell activation markers CD25 and CD69 on CD4+ and CD8+ T cells was also increased upon SP muromonab-CD3 stimulation.Using multiplex cytokine assessment, we showed that stimulation in AP using ANC28.1, CD28.2 and muromonab-CD3 led to an increase of IFN-ɣ, GM-CSF, TNF-α, and IL-2 secretion.Stimulation of PBMCs preincubated at high-density culture led to an increase in IFN-ɣ production but not in the expression of activation markers compared to low-density culture.Our findings demonstrated that flow cytometry analyses for assessing relevant T cell and NK cell markers may be used as a supplement to multiplex cytokine analysis in CRAs. The approach may be a valuable addition that enables a more precise description of the mechanisms leading to CRS.

Sample displacement chromatography of monoclonal antibody charge variants and aggregates.

The rise of biosimilar monoclonal antibodies has renewed the interest in monoclonal antibody (mAb) charge variants composition and separation. The sample displacement chromatography (SDC) has the potential to overcome the low separation efficiency and productivity associated with bind-elute separation of mAb charge variants. SDC in combination with weak cation exchanging macroporous monolithic chromatographic column was successfully implemented for a separation of charge variants and aggregates of monoclonal IgG under overloading conditions. The charge variants composition was at-line monitored by a newly developed, simple and fast analytical method, based on weak cation exchange chromatography. It was proven that basic charge variants acted as displacers of IgG molecules with lower pI, when the loading was performed 1 to 1.5pH unit below the pI of acidic charge variants. The efficiency of the SDC process is flow rate independent due to a convection-based mass transfer on the macroporous monolith. The productivity of the process at optimal conditions is 35mg of purified IgG fraction per milliliters of monolithic support with 75-80% recovery. As such, an SDC approach surpasses the standard bind-elute separation in the productivity for a factor of 3, when performed on the same column. The applicability of the SDC approach was confirmed for porous particle-based column as well, but with 1.5 lower productivity compared to the monoliths.

Evolving Perceptions, Utilization, and Real-World Implementation Experiences of Oncology Monoclonal Antibody Biosimilars in the USA: Perspectives from Both Payers and Physicians.

BackgroundThe adoption of oncology biosimilars has been slow in the USA, which may be attributed in part to stakeholder perceptions and lack of operational guidance that supports favorable access to biosimilars.ObjectiveOur objective was to understand the real-world implementation experiences with oncology biosimilars of US payers and healthcare professionals (HCPs) as their experience with biosimilars has evolved.MethodsIn-depth qualitative interviews with payers (n = 20) and HCPs (n = 17 physicians, n = 3 practice managers) were conducted. Payers included managed care organizations (MCOs), integrated delivery networks, and pharmacy benefit managers (PBMs). Physicians were affiliated with a healthcare network or were community based, specialized in hematology/oncology, and had prescribed oncology biosimilars. Audio transcripts of the interviews were coded using MaxQDA software to enable descriptive analysis of the qualitative data.ResultsOver 80.0% of physicians perceived the efficacy and safety of biosimilars to be highly comparable to that of originators. Up to 87.5% of physicians reported using biosimilars in > 50% of their treatment-naïve patients and were comfortable using biosimilars in all approved indications. To encourage utilization, 75.0% of MCOs/PBMs preferred biosimilars over originators in treatment-naïve patients and implementation via step therapy. Physician involvement in choosing biosimilars was minimal, which was largely dependent on practice protocols or insurance preferences. The major factor influencing payers’ coverage decisions and biosimilar adoption was potential cost savings.ConclusionsUS payers and physicians who have experience with biosimilars have favorable views of oncology biosimilars, particularly for treatment-naïve patients. A framework for integrating biosimilars into oncology practice is developing, primarily driven by insurance coverage, contracting, and cost benefits.

Safety, Immunogenicity and Interchangeability of Biosimilar Monoclonal Antibodies and Fusion Proteins: A Regulatory Perspective.

BackgroundBiosimilars have been used for 15 years in the European Union (EU), and have been shown to reduce costs and increase access to important biological medicines. In spite of their considerable exposure and excellent safety record, many prescribers still have doubts on the safety and interchangeability of biosimilars, especially monoclonal antibodies (mAbs) and fusion proteins.ObjectivesThe aim of this study was to analyse the short- and long-term safety and interchangeability data of biosimilar mAbs and fusion proteins to provide unbiased information to prescribers and policy makers.MethodsData on the safety, immunogenicity and interchangeability of EU-licensed mAbs and fusion proteins were examined using European Public Assessment Reports (EPARs) and postmarketing safety surveillance reports from the European Medicines Agency (EMA). As recent biosimilar approvals allow self-administration by patients by the subcutaneous route, the administration devices were also analyzed.ResultsPrelicensing data of EPARs (six different biosimilar adalimumabs, three infliximabs, three etanercepts, three rituximabs, two bevacizumabs, and six trastuzumabs) revealed that the frequency of fatal treatment-emergent adverse events (TEAEs), TEAEs leading to discontinuation of treatment, serious adverse events (SAEs), and main immune-mediated adverse events (AEs) were comparable between the biosimilars and their reference products. The availability of new biosimilar presentations and administration devices may add to patient choice and be an emerging factor in the decision to switch patients. Analysis of postmarketing surveillance data covering up to 7 years of follow-up did not reveal any biosimilar-specific adverse effects. No product was withdrawn for safety reasons. This is in spite of considerable exposure to biosimilars in treatment-naïve patients and in patients switched from the reference medicinal product to the biosimilar. Analysis of data from switching studies provided in regulatory submissions showed that single or multiple switches between the originator and its biosimilar versions had no negative impact on efficacy, safety or immunogenicity.ConclusionsIn line with previous reports of prelicensing studies of biosimilar mAbs and etanercepts, this study demonstrated comparable efficacy, safety, and immunogenicity compared with the reference products. This is the first study to comprehensively analyze postmarketing surveillance data of the biosimilar mAbs and etanercept. An analysis of more than 1 million patient-treatment years of safety data raised no safety concerns. Based on these data, we argue that biosimilars approved in the EU are highly similar to and interchangeable with their reference products. Thus, additional systematic switch studies are not required to support the switching of patients.Supplementary InformationThe online version contains supplementary material available at 10.1007/s40265-021-01601-2.

Evaluation of real-world cost savings and utilization of biosimilar drugs in a community-based oncology practice.

73 Background: Biosimilar drugs, defined as biologic products with no clinically significant differences in quality, efficacy and safety compared to approved reference products have gained increasing adoption based on studies projecting significant cost savings[1]. Real world evaluation of biosimilar related cost savings and adoption is however still limited. We prospectively evaluate cost savings generated by transitioning to biosimilar monoclonal antibodies in a community based oncology practice. Methods: In July 2020, a process for transitioning patients to biosimilar equivalents of Rituximab, Trastuzumab and Bevacizumab was implemented in a community based oncology practice. Provider adoption was facilitated by monthly oncology pharmacy governance meetings that allowed provider participation and feedback followed by defaulting the preferred biosimilar product in oncology chemotherapy software (Epic Beacon, Epic Systems, Verona, WI). The treatment templates allowed for care personalization by listing reference products that could be chosen if desired. Cost savings achieved by switching to biosimilars was calculated by subtracting the actual spending on the biosimilar product from projected acquisition cost of the branded reference product (Table). Biosimilar adoption, defined as amount of biosimilar drug used over total amount of the drug ordered was also calculated. Results: Between July 2020 and April 2021, transitioning to biosimilar products for Rituximab, Bevacizumab and Trastuzumab resulted in net savings of $268,194.64, $285,251.89 and $274,359.51 respectively. Actual spending on Rituximab biosimilar product was $726,476.10 against a projected spending of $994,670.74 on the branded reference product. Actual spending on Bevacizumab biosimilar product was $1,254,977.30 against a projected spending of $1,540,229.19 on the branded reference product. Actual spending on Trastuzumab biosimilar product was $1,218,641.60 against a projected spending of $1,493,001.11 on the branded product. Average biosimilar utilization between October 2020 and April 2020 has been 92%, 100% and 98% for Rituximab, Bevacizumab and Trastuzumab respectively. Conclusions: Significant cost-savings can result from widespread utilization of biosimilar drugs in community oncology practices.

Mechanistic modeling of continuous capture step purification of biosimilar monoclonal antibody therapeutic

AbstractBACKGROUNDContinuous multicolumn Protein A chromatography offers various advantages for capture stage purification of monoclonal antibody therapeutics, like higher productivity and resin capacity utilization, lower buffer consumption, small footprint, etc. Due to the complexity of the continuous process, experimental optimization is time‐consuming and cost‐intensive. This investigation proposes a hybrid process development approach integrating experimental and mechanistic modeling for time‐ and cost‐effective development and optimization of continuous Protein A affinity chromatography.RESULTSProductivity and capacity utilization of the continuous CaptureSMB process under varying operating conditions were predicted using the Chromatography Analysis and Design Toolkit (CADET) framework and validated with experimental results. Effects of critical process parameters like feed concentration (c0), loading breakthrough (s) and residence time (RT) on productivity and capacity utilization were evaluated. Model predictions were validated using the experimental results proving the reliability and feasibility of the modeling approach. At 15.00 ± 0.20 mg mL–1 feed model mAb concentration, the model‐based approach predicted the best performance giving 27.56 g L–1 h–1 productivity (RT = 2 min, s = 80%) using MabSelect™ PrismA resin. This productivity prediction was validated by performing the continuous CaptureSMB experiment at the same operating conditions and was found to be 25.59 g L–1 h–1 with a root mean square error of 1.96.CONCLUSIONSThe hybrid process development and optimization approach for CaptureSMB purification of biosimilar mAb purification is demonstrated and validated using the experimental and model‐based framework. The observed results showcase the effectiveness of the proposed hybrid process development approach, enabling a better understanding of the chromatography process and parameters affecting the CaptureSMB process. © 2021 Society of Chemical Industry (SCI).

Adalimumab biosimilar in inflammatory bowel disease

The use of biosimilars of monoclonal antibodies against TNFα is one of the key pillars in the treatment of inflammatory bowel disease (IBD), and, more generally, in all immune-mediated diseases. In relation to IBD, the Biosimilar Council estimated that the increasing availability of biosimilars has provided a potential saving between US$53 and $106 billion in western Europe and the USA between 2015 and 2020.1 The substantial cost reduction for treating IBD has increased access to biologics, leading to improvements in clinical outcomes for patients and greater health-care system efficiency.

Real-world use and acceptance of biosimilar monoclonal antibodiesof rituximab in oncology practice in the USA.

Aim: To describe treatment patterns and patient and provider characteristics associated with the recently introduced biosimilarrituximab-pvvr. Methods: This retrospective analysis included adult patients with one or more claims for rituximab-pvvr, withan index date of 23January 2020and astudy period covering 1January2019-31July2020. Results: Of 249 patients included, the most common rituximab-pvvr indications were non-Hodgkin's lymphoma (77.5%) and chronic lymphocytic leukemia (11.2%). Some patients withnon-Hodgkin's lymphoma (42.5%) and chronic lymphocytic leukemia(39.3%) switched to rituximab-pvvr from the reference product or another rituximab biosimilar. Most patients were aged ≥65years (63.5%) and weremale (54.6%). Most (59.0%) rituximab-pvvr prescribers practiced in the south of the USA. Conclusion: Utilization occurred in approved and extrapolated indications. These preliminary findings suggest switching between reference product and rituximab biosimilars;rituximab-pvvr combination regimensare being adopted in real-world oncology practice.

Cetuximab produced from a goat mammary gland expression system is equally efficacious as innovator cetuximab in animal cancer models

There is increasing demand for improved production and purification systems for biosimilar or biobetter humanised monoclonal antibodies and animal production systems offer one such possibile option. Cetuximab, also known as ‘Erbitux’, is a humanised monoclonal antibody widely used in cancer therapy. We have previously reported on a genetically engineered goat system to produce cetuximab (gCetuximab) in milk. Herein we report that gCetuximab has similar bioactivity and pharamacokinetic properties compared with the commercial product produced in mammalian cell culture. In particular both forms have very similar efficacy in a HT29 colorectal cancer xenograft model alone or when conjugated to the toxin MMAE. This also demonstrates that the gCetuximab will be a viable vehicle for antibody drug conjugate based therapies. Taken together, this shows that the goat milk monoclonal antibody production system is an effective way of producing a biosimilar form of cetuximab.

Budget Impact Analysis of Switching to Rituximab's Biosimilar in Rheumatology and Cancer in 13 Countries Within the Middle East and North Africa.

IntroductionBiosimilars of monoclonal antibodies are being rapidly developed and approved by public health regulatory authorities worldwide. These biosimilars are expected to bring significant budgetary savings to national governments and consequently increase patients’ accessibility to biological therapy. Rituximab has been used extensively for the treatment of cancer and rheumatoid disorders over the past two decades. New biosimilars of Rituximab have been developed and introduced into clinical practice. We have analyzed the budgetary impact and savings outcome of introducing Rituximab’s biosimilar into 13 countries within the Middle East and North Africa through the implementation of a budget impact analysis model.MethodsOur model was based on a 1-year full uptake and switch scenario of the Rituximab’s biosimilar CT-P10. The model calculated the total number of patients based on the total national consumption of Rituximab per country. Accordingly, the model produced savings per each indication which were translated into the additional number of patients that would be permitted access to Rituximab’s therapy as a result of these savings.ResultsIn our modeling scenario, the total projected savings that will result from the uptake of Rituximab’s biosimilar within the MENA region were estimated to be 46.59 million dollars. The cumulative savings in all 13 countries would allow access of Rituximab’s therapy for a total of 6589 patients which is equivalent to a 14% increase in the number of patients benefiting from Rituximab’s therapy.ConclusionThe introduction of Rituximab’s biosimilar within the Middle East and North Africa region is associated with significant budgetary savings that will allow public national health authorities to reinvest such economic gains either in expanding access to Rituximab therapy or other costly lifesaving biologicals.

Clustering and curation of electropherograms: an efficient method for analyzing large cohorts of capillary electrophoresis glycomic profiles for bioprocessing operations.

The accurate assessment of antibody glycosylation during bioprocessing requires the high-throughput generation of large amounts of glycomics data. This allows bioprocess engineers to identify critical process parameters that control the glycosylation critical quality attributes. The advances made in protocols for capillary electrophoresis-laser-induced fluorescence (CE-LIF) measurements of antibody N-glycans have increased the potential for generating large datasets of N-glycosylation values for assessment. With large cohorts of CE-LIF data, peak picking and peak area calculations still remain a problem for fast and accurate quantitation, despite the presence of internal and external standards to reduce misalignment for the qualitative analysis. The peak picking and area calculation problems are often due to fluctuations introduced by varying process conditions resulting in heterogeneous peak shapes. Additionally, peaks with co-eluting glycans can produce peaks of a non-Gaussian nature in some process conditions and not in others. Here, we describe an approach to quantitatively and qualitatively curate large cohort CE-LIF glycomics data. For glycan identification, a previously reported method based on internal triple standards is used. For determining the glycan relative quantities our method uses a clustering algorithm to ‘divide and conquer’ highly heterogeneous electropherograms into similar groups, making it easier to define peaks manually. Open-source software is then used to determine peak areas of the manually defined peaks. We successfully applied this semi-automated method to a dataset (containing 391 glycoprofiles) of monoclonal antibody biosimilars from a bioreactor optimization study. The key advantage of this computational approach is that all runs can be analyzed simultaneously with high accuracy in glycan identification and quantitation and there is no theoretical limit to the scale of this method.

Evaluation of different IRES-mediated tricistronic plasmid designs for expression of an anti-PCSK9 biosimilar monoclonal antibody in CHO cells.

To compare different approaches for the expression of an anti-PCSK9 biosimilar monoclonal antibody (mAb) in CHO cells using IRES-mediated tricistronic plasmid vectors combining different signal peptides, IRES elements and selection markers. Transient transfection indicated a similar level of secreted mAb 48h post-transfection for all constructs. However, transfections carried out with circular plasmids showed a higher expression than with linearized plasmids. After two months under selection pressure, only part of the transfected pools recovered. The cultures co-transfected using two antibiotics as selection markers for double selection did not recover. Growth, metabolism and mAb production profiles of the only part of the transfected pools recovered resulting stable pools were compared and the stable pool transfected with circular L1-LC-IRES-H7-HC-IRES-NEO plasmid was chosen for further studies, due to higher cell growth and mAb production. Critical quality attributes of the protein A-purified mAb such as purity, homogeneity, binding affinity to PCSK9, and amino acid sequence were assessed confirming the success of the approach adopted in this study. The expression platform proposed showed to be efficient to produce a high-quality anti-PCSK9 mAb in stable CHO cell pools and provides benchmarks for fast production of different mAbs for characterization, formulation studies and pre-clinical investigation.

First-line therapy of indolent non-Hodgkin’s lymphoma in routine clinical practice

The aim is to evaluate the efficacy of the first-line rituximab-containing therapy of B-cell lymphoproliferative diseases in Russian clinical practice between 2014 and 2017.
 Materials and methods. In the post-authorisation multicenter study EQUILIBRIUM were included 1 thousand patients aged from 21 to 91 with B-cell non-Hodgkins lymphoma or chronic lymphatic leukemia who had received at least 4 cycles of rituximab-containing therapy using the drug Acellbia. This article was devoted to the group of indolent non-Hodgkins lymphomas and included 253 patients: follicular lymphoma 51% of cases, marginal zone lymphoma 44% of patients, extremely rare were registered lymphoplasmacytic lymphoma and Waldenstrom macroglobulinemia in 3% and in 2% of cases, respectively. The median age in patients with indolent non-Hodgkins lymphomas was 62 years (2191 years). The vast majority of patients were diagnosed with stage IIIIV 190 (75%) of patients. More than 1/2 (53.4%) of patients in routine practice received R-CHOP therapy as a first-line. BR regimen was applied in 15.4% of cases, 14.2% of patients were treated with R-CVP/R-COP. We indicated rare use of rituximab as monotherapy in induction mode only 4.4% of patients. And 2.4% of patients were treated with fludarabine-containing therapy.
 Results. The final assessment of the effect was carried out after 68 cycles of treatment and as a result the overall effect was more than 90%: the frequency of complete remission was 61%, partial responses 32.9%. The progression admitted only in 17 (6.7%) patients among 253 observed. With a median of 15 months, the median of overall survival and event-free survival was not achieved.
 Conclusion. The use of the available and appropriate treatment according to the domestic clinical guidelines with the inclusion of the Russian biosimilar anti-CD20 monoclonal antibody Acellbia, demonstrates high direct efficacy and satisfactory long-term treatment results comparable to the retrospective analysis of the previous clinical studies of the original drug rituximab.

A randomized phase I clinical trial comparing the pharmacokinetic, safety, and immunogenicity of potential biosimilar recombinant human HER2 monoclonal antibody for injection and trastuzumab in healthy Chinese adults

ABSTRACT Objectives Recombinant human HER2 monoclonal antibody for injection (AK-HER2) is a potential biosimilar of trastuzumab (Herceptin®). This phase Ⅰ study aimed to demonstrate the pharmacokinetic (PK) equivalence between AK-HER2 and trastuzumab in healthy volunteers. Besides, safety and immunogenicity were investigated. Research design and methods This was a randomized, double-blind phase Ⅰ trial in 96 healthy adults who received a single intravenous infusion of AK-HER2 or trastuzumab at 6 mg/kg. The primary PK endpoints were area under the serum concentration curve (AUC) from time 0 to the last time point (AUC0-t) and peak concentration in serum (Cmax). The PK bioequivalence was confirmed using the standard equivalence margins of 80%-125%. Results The PK profiles of AK-HER2 and trastuzumab displayed high similarity. The geometric mean ratios (90% confidence intervals) of primary PK endpoints were within 80%-125%. The C max and AUC 0-t of female subjects in the AK-HER2 group were greater than those of male subjects (P <0.05). No infusion-related reactions (IRRs) or anti-drug antibody-positivity was observed after dosing. Conclusions AK-HER2 was demonstrated to have highly similar PK to trastuzumab in healthy Chinese adults. Both drugs showed comparable safety and immunogenicity using dexamethasone as premedication to prevent IRRs..

Quality by Design\u2013Based Assessment for Analytical Similarity of Adalimumab Biosimilar HLX03 to Humira\xae

Quality by design (QbD) is an efficient but challenging approach for the development of biosimilar due to the complex relationship among process, quality, and efficacy. Here, the analytical similarity of adalimumab biosimilar HLX03 to Humira® was successfully established following a QbD quality study. Quality target product profile (QTPP) of HLX03 was first generated according to the public available information and initial characterization of 3 batches of Humira®. The critical quality attributes (CQAs) were then identified through risk assessment according to impact of each quality attribute on efficacy and safety. The anticipated range for each CQA was derived from similarity acceptance range and/or the corresponding regulatory guidelines. Finally, a panel of advanced and orthogonal physicochemical and functional tests and comparison of 6 batches of HLX03 and 10 batches of the reference standard demonstrated high similarity of HLX03 to Humira®, except for slightly lower percentage of high mannosylated glycans (%HM) in HLX03 which had no effect on FcγRIII binding and antibody-dependent cell-mediated cytotoxicity (ADCC) activity in human peripheral blood mononuclear cell (PBMC). All above demonstrated the feasibility and efficiency of QbD-based similarity assessment of a biosimilar monoclonal antibody (mAb).

Biosimilars of monoclonal antibodies in inflammatory diseases and cancer: current situation, challenges, and opportunities.

The approval pathway for biosimilars of monoclonal antibodies in theEuropeanUnion is aimed at ruling out the presence of significant differenceswith the original biological in quality attributes, efficacy, immunogenicityand safety. It also provides the rationale for extrapolating the evidenceobtained with a biosimilar in at least one indication to the rest of theapproved indications of its original biological, thus simplifying the developmentprogramme of biosimilars. Biosimilars of monoclonal antibodiesavailable in the European Union for the treatment of inflammatory diseasesand cancer have fulfilled all the requirements for approval, and manyof them have additional evidence available. Moreover, real world dataconfirms the safety and efficacy of these drugs in the indications they arebeing used for. In Spain, many scientific societies endorse the regulatorypathway of biosimilars and acknowledge their role in the efficiency of thehealthcare system. Even so, some barriers remain that limit their use. Theimplementation of different measures at the patient, prescriber, institutional, and national levels might increase the penetration of biosimilars, freeing up resources that may be invested in other therapies and, potentially, boost innovation.

Biosimilar monoclonal antibodies for cancer treatment

Biosimilar monoclonal antibodies for cancer treatment