26 results on '"Biosimilars"'
Search Results
2. Population Pharmacokinetic Analysis and Simulation of Alternative Dosing Regimens for Biosimilars to Adalimumab and Etanercept in Patients with Rheumatoid Arthritis.
- Author
-
Ling, Stephanie F., Ogungbenro, Kayode, Darwich, Adam S., Ariff, Amirah Binti Mohammad, Nair, Nisha, Bluett, James, Morgan, Ann W., Isaacs, John D., Wilson, Anthony G., Hyrich, Kimme L., Barton, Anne, and Plant, Darren
- Subjects
- *
ADALIMUMAB , *BIOSIMILARS , *RHEUMATOID arthritis , *ETANERCEPT , *PHARMACOKINETICS , *BIOLOGICALS - Abstract
Efficacy to biologics in rheumatoid arthritis (RA) patients is variable and is likely influenced by each patient's circulating drug levels. Using modelling and simulation, the aim of this study was to investigate whether adalimumab and etanercept biosimilar dosing intervals can be altered to achieve therapeutic drug levels at a faster/similar time compared to the recommended interval. RA patients starting subcutaneous Amgevita or Benepali (adalimumab and etanercept biosimilars, respectively) were recruited and underwent sparse serum sampling for drug concentrations. Drug levels were measured using commercially available kits. Pharmacokinetic data were analysed using a population approach (popPK) and potential covariates were investigated in models. Models were compared using goodness-of-fit criteria. Final models were selected and used to simulate alternative dosing intervals. Ten RA patients starting the adalimumab biosimilar and six patients starting the etanercept biosimilar were recruited. One-compartment PK models were used to describe the popPK models for both drugs; no significant covariates were found. Typical individual parameter estimates were used to simulate altered dosing intervals for both drugs. A simulation of dosing the etanercept biosimilar at a lower rate of every 10 days reached steady-state concentrations earlier than the usual dosing rate of every 7 days. Simulations of altered dosing intervals could form the basis for future personalised dosing studies, potentially saving costs whilst increasing efficacy. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
3. Trends in Targeted Therapy Usage in Inflammatory Bowel Disease: TRENDY Study of ENEIDA.
- Author
-
Gómez-Labrador, Celia, Ricart, Elena, Iborra, Marisa, Iglesias, Eva, Martín-Arranz, María Dolores, de Castro, Luisa, De Francisco, Ruth, García-Alonso, Francisco Javier, Sanahuja, Ana, Gargallo-Puyuelo, Carla J., Mesonero, Francisco, Casanova, María José, Mañosa, Míriam, Rivero, Montserrat, Calvo, Marta, Sierra-Ausin, Mónica, González-Muñoza, Carlos, Calvet, Xavier, García-López, Santiago, and Guardiola, Jordi
- Subjects
- *
INFLAMMATORY bowel diseases , *CROHN'S disease , *MACHINE learning , *ULCERATIVE colitis , *BIOSIMILARS - Abstract
Markers that allow for the selection of tailored treatments for individual patients with inflammatory bowel diseases (IBD) are yet to be identified. Our aim was to describe trends in real-life treatment usage. For this purpose, patients from the ENEIDA registry who received their first targeted IBD treatment (biologics or tofacitinib) between 2015 and 2021 were included. A subsequent analysis with Machine Learning models was performed. The study included 10,009 patients [71% with Crohn's disease (CD) and 29% with ulcerative colitis (UC)]. In CD, anti-TNF (predominantly adalimumab) were the main agents in the 1st line of treatment (LoT), although their use declined over time. In UC, anti-TNF (mainly infliximab) use was predominant in 1st LoT, remaining stable over time. Ustekinumab and vedolizumab were the most prescribed drugs in 2nd and 3rd LoT in CD and UC, respectively. Overall, the use of biosimilars increased over time. Machine Learning failed to identify a model capable of predicting treatment patterns. In conclusion, drug positioning is different in CD and UC. Anti-TNF were the most used drugs in IBD 1st LoT, being adalimumab predominant in CD and infliximab in UC. Ustekinumab and vedolizumab have gained importance in CD and UC, respectively. The approval of biosimilars had a significant impact on treatment. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
4. A Regulatory Perspective on Biosimilar Medicines.
- Author
-
Cordeiro, Marta Agostinho, Vitorino, Carla, Sinogas, Carlos, and Sousa, João J.
- Subjects
- *
BIOSIMILARS , *GENERIC drugs , *CHEMICAL processes , *MANUFACTURING processes , *MEDICAL personnel , *GOVERNMENT agencies - Abstract
By definition, biosimilar medicinal products are biological medicinal products that are similar to other biological medicinal products that are already on the market—the reference medicinal products. Access to biosimilar medicines is a current reality. However, to achieve this goal, it is extremely important to consistently and scientifically substantiate the regulatory requirements necessary for biosimilar medicines when accessing the market. Based on an analysis of the raw materials and the type of methods used in the manufacturing processes of biological medicines, it is known that this tends to be more complex for the quality of the finished product than the manufacture of molecules obtained through a chemical process. It is then relevant to highlight the main differences between both products: biological medicines manufactured using biotechnology and the current generics containing active pharmaceutical ingredients (APIs) obtained from synthetic processes. Once arriving at the approval process of these medicinal products, it is imperative to analyse the guidance documents and the regulatory framework that create the rules that allow these biosimilar medicinal products to come to the market. The present review aimed at documenting comparatively the specific provisions of European legislation, through the European Medicines Agency (EMA), as well as the legislation of the United States of America, through the Food and Drug Administration (FDA). This was then translated into a critical appraisal of what concerns the specific criteria that determine the favourable evaluation of a biosimilar when an application for marketing authorisation is submitted to different regulatory agencies. The gathered evidence suggests that the key to the success of biosimilar medicines lies in a more rigorous and universal regulation as well as a greater knowledge, acceptance, and awareness of health professionals to enable more patients to be treated with biological strategies at an earlier stage of the disease and with more affordable medicines, ensuring always the safety and efficacy of those medicines. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
5. Advice to the US FDA to Allow US Pharmacopeia to Create Biological Product Specifications (BPS) to Remove Side-by-Side Analytical Comparisons of Biosimilars with Reference Products
- Author
-
Sarfaraz K. Niazi
- Subjects
biosimilars ,FDA ,US Pharmacopoeia (USP 2024) ,biological product specification (BPS) ,novel monograph ,side-by-side reference product testing ,Pharmacy and materia medica ,RS1-441 - Abstract
Pharmacopeia monographs are not intended to establish biosimilarity. However, the US Food and Drug Administration (FDA) has stopped the US Pharmacopeia (USP) from creating monographs for biological drugs due to the need for side-by-side comparisons with the reference products. The USP can create Biological Product Specifications (BPS), not to be labeled as monographs, based on the analytical testing of reference products and validated test methods that will remove the need for side-by-side analytical testing of biosimilars with reference products. Scientific arguments confirm that this plan is logical and capable of creating global quality standards for biosimilars to allow their interchangeability with other biosimilars. While the regulatory agencies have waived many high-cost biosimilar tests, analytical assessment is the most sensitive test; reducing its cost will further enhance the entry of biosimilars with no clinically meaningful difference.
- Published
- 2024
- Full Text
- View/download PDF
6. Population Pharmacodynamic Modelling of the CD19+ Suppression Effects of Rituximab in Paediatric Patients with Neurological and Autoimmune Diseases.
- Author
-
Riva, Natalia, Brstilo, Lucas, Sancho-Araiz, Aymara, Molina, Manuel, Savransky, Andrea, Roffé, Georgina, Sanz, Marianela, Tenembaum, Silvia, Katsicas, Maria M., Trocóniz, Iñaki F., and Schaiquevich, Paula
- Subjects
- *
RITUXIMAB , *CD19 antigen , *CHILD patients , *AUTOIMMUNE diseases , *NEUROLOGICAL disorders , *BIOSIMILARS - Abstract
Background: Limited pharmacotherapy and the failure of conventional treatments in complex pathologies in children lead to increased off-label use of rituximab. We aimed to characterize the time course of CD19+ B lymphocytes (CD19+) under treatment with intravenous rituximab in children with neurologic and autoimmune diseases and to evaluate the impact of covariates (i.e., demographics, diagnosis and substitution between innovator and biosimilar product) on rituximab pharmacodynamics and disease activity. Methods: Pre- and post-drug infusion CD19+ in peripheral blood were prospectively registered. A population pharmacodynamic model describing the time course of CD19+ was developed with NONMEM v7.4. Simulations of three different rituximab regimens were performed to assess the impact on CD19+. Logistic regression analysis was performed to identify predictors of clinical response recorded through disease activity scores. Results: 281 measurements of CD19+ lymphocyte counts obtained from 63 children with neurologic (n = 36) and autoimmune (n = 27) diseases were available. The time course of CD19+ was described with a turn-over model in which the balance between synthesis and degradation rates is disrupted by rituximab, increasing the latter process. The model predicts half-lives (percent coefficient of variation, CV(%)) of rituximab and CD19+ of 11.6 days (17%) and 173.3 days (22%), respectively. No statistically significant effect was found between any of the studied covariates and model parameters (p > 0.05). Simulations of different regimens showed no clinically significant differences in terms of CD19+ repopulation times. A trend towards a lack of clinical response was observed in patients with lower CD19+ repopulation times and higher areas under the CD19+ versus time curve. Conclusions: Rituximab pharmacodynamics was described in a real-world setting in children suffering from autoimmune and neurologic diseases. Diagnosis, substitution between innovator rituximab and its biosimilars or type of regimen did not affect rituximab-induced depletion of CD19+ nor the clinical response in this cohort of patients. According to this study, rituximab frequency and dosage may be chosen based on clinical convenience or safety reasons without affecting CD19+ repopulation times. Further studies in larger populations are required to confirm these results. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
7. Population Pharmacokinetic Analysis and Simulation of Alternative Dosing Regimens for Biosimilars to Adalimumab and Etanercept in Patients with Rheumatoid Arthritis
- Author
-
Stephanie F. Ling, Kayode Ogungbenro, Adam S. Darwich, Amirah Binti Mohammad Ariff, Nisha Nair, James Bluett, Ann W. Morgan, John D. Isaacs, Anthony G. Wilson, Kimme L. Hyrich, Anne Barton, and Darren Plant
- Subjects
rheumatoid arthritis ,pharmacokinetics ,population pharmacokinetics ,simulation ,biologics ,biosimilars ,Pharmacy and materia medica ,RS1-441 - Abstract
Efficacy to biologics in rheumatoid arthritis (RA) patients is variable and is likely influenced by each patient’s circulating drug levels. Using modelling and simulation, the aim of this study was to investigate whether adalimumab and etanercept biosimilar dosing intervals can be altered to achieve therapeutic drug levels at a faster/similar time compared to the recommended interval. RA patients starting subcutaneous Amgevita or Benepali (adalimumab and etanercept biosimilars, respectively) were recruited and underwent sparse serum sampling for drug concentrations. Drug levels were measured using commercially available kits. Pharmacokinetic data were analysed using a population approach (popPK) and potential covariates were investigated in models. Models were compared using goodness-of-fit criteria. Final models were selected and used to simulate alternative dosing intervals. Ten RA patients starting the adalimumab biosimilar and six patients starting the etanercept biosimilar were recruited. One-compartment PK models were used to describe the popPK models for both drugs; no significant covariates were found. Typical individual parameter estimates were used to simulate altered dosing intervals for both drugs. A simulation of dosing the etanercept biosimilar at a lower rate of every 10 days reached steady-state concentrations earlier than the usual dosing rate of every 7 days. Simulations of altered dosing intervals could form the basis for future personalised dosing studies, potentially saving costs whilst increasing efficacy.
- Published
- 2024
- Full Text
- View/download PDF
8. Trends in Targeted Therapy Usage in Inflammatory Bowel Disease: TRENDY Study of ENEIDA
- Author
-
Celia Gómez-Labrador, Elena Ricart, Marisa Iborra, Eva Iglesias, María Dolores Martín-Arranz, Luisa de Castro, Ruth De Francisco, Francisco Javier García-Alonso, Ana Sanahuja, Carla J. Gargallo-Puyuelo, Francisco Mesonero, María José Casanova, Míriam Mañosa, Montserrat Rivero, Marta Calvo, Mónica Sierra-Ausin, Carlos González-Muñoza, Xavier Calvet, Santiago García-López, Jordi Guardiola, Lara Arias García, Lucía Márquez-Mosquera, Ana Gutiérrez, Yamile Zabana, Mercè Navarro-Llavat, Rufo Lorente Poyatos, Marta Piqueras, Leyanira Torrealba, Fernando Bermejo, Ángel Ponferrada-Díaz, José L. Pérez-Calle, Manuel Barreiro-de Acosta, Coral Tejido, José Luis Cabriada, Ignacio Marín-Jiménez, Óscar Roncero, Yolanda Ber, Luis Fernández-Salazar, Blau Camps Aler, Alfredo J. Lucendo, Jordina Llaó, Luis Bujanda, Carmen Muñoz Villafranca, Eugeni Domènech, María Chaparro, and Javier P. Gisbert
- Subjects
biologics ,biosimilars ,targeted therapy ,inflammatory bowel disease ,Crohn’s disease ,ulcerative colitis ,Pharmacy and materia medica ,RS1-441 - Abstract
Markers that allow for the selection of tailored treatments for individual patients with inflammatory bowel diseases (IBD) are yet to be identified. Our aim was to describe trends in real-life treatment usage. For this purpose, patients from the ENEIDA registry who received their first targeted IBD treatment (biologics or tofacitinib) between 2015 and 2021 were included. A subsequent analysis with Machine Learning models was performed. The study included 10,009 patients [71% with Crohn’s disease (CD) and 29% with ulcerative colitis (UC)]. In CD, anti-TNF (predominantly adalimumab) were the main agents in the 1st line of treatment (LoT), although their use declined over time. In UC, anti-TNF (mainly infliximab) use was predominant in 1st LoT, remaining stable over time. Ustekinumab and vedolizumab were the most prescribed drugs in 2nd and 3rd LoT in CD and UC, respectively. Overall, the use of biosimilars increased over time. Machine Learning failed to identify a model capable of predicting treatment patterns. In conclusion, drug positioning is different in CD and UC. Anti-TNF were the most used drugs in IBD 1st LoT, being adalimumab predominant in CD and infliximab in UC. Ustekinumab and vedolizumab have gained importance in CD and UC, respectively. The approval of biosimilars had a significant impact on treatment.
- Published
- 2024
- Full Text
- View/download PDF
9. Biosimilars in Oncology: Latest Trends and Regulatory Status.
- Author
-
Joshi, Deeksha, Khursheed, Rubiya, Gupta, Saurabh, Wadhwa, Diksha, Singh, Thakur Gurjeet, Sharma, Sumit, Porwal, Sejal, Gauniyal, Swati, Vishwas, Sukriti, Goyal, Sanjay, Gupta, Gaurav, Eri, Rajaraman D., Williams, Kylie A., Dua, Kamal, and Singh, Sachin Kumar
- Subjects
- *
MEDICAL personnel , *BIOSIMILARS , *FUTURES sales & prices , *PATIENT decision making , *ONCOLOGY , *ANTIRHEUMATIC agents - Abstract
Biologic-based medicines are used to treat a variety of diseases and account for around one-quarter of the worldwide pharmaceutical market. The use of biologic medications among cancer patients has resulted in substantial advancements in cancer treatment and supportive care. Biosimilar medications (or biosimilars) are very similar to the reference biologic drugs, although they are not identical. As patent protection for some of the most extensively used biologics begins to expire, biosimilars have the potential to enhance access and provide lower-cost options for cancer treatment. Initially, regulatory guidelines were set up in Europe in 2003, and the first biosimilar was approved in 2006 in Europe. Many countries, including the United States of America (USA), Canada, and Japan, have adopted Europe's worldwide regulatory framework. The use of numerous biosimilars in the treatment and supportive care of cancer has been approved and, indeed, the count is set to climb in the future around the world. However, there are many challenges associated with biosimilars, such as cost, immunogenicity, lack of awareness, extrapolation of indications, and interchangeability. The purpose of this review is to provide an insight into biosimilars, which include various options available for oncology, and the associated adverse events. We compare the regulatory guidelines for biosimilars across the world, and also present the latest trends and challenges in medical oncology both now and in the future, which will assist healthcare professionals, payers, and patients in making informed decisions, increasing the acceptance of biosimilars in clinical practice, increasing accessibility, and speeding up the health and economic benefits associated with biosimilars. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
10. Under the Umbrella of Clinical Pharmacology: Inflammatory Bowel Disease, Infliximab and Adalimumab, and a Bridge to an Era of Biosimilars.
- Author
-
Petric, Zvonimir, Goncalves, Joao, and Paixao, Paulo
- Subjects
- *
INFLAMMATORY bowel diseases , *CROHN'S disease , *CLINICAL pharmacology , *BIOSIMILARS , *ULCERATIVE colitis , *ADALIMUMAB - Abstract
Monoclonal antibodies (MAbs) have revolutionized the treatment of many chronic inflammatory diseases, including inflammatory bowel disease (IBD). IBD is a term that comprises two quite similar, yet distinctive, disorders—Crohn's disease (CD) and ulcerative colitis (UC). Two blockbuster MAbs, infliximab (IFX) and adalimumab (ADL), transformed the pharmacological approach of treating CD and UC. However, due to the complex interplay of pharmacology and immunology, MAbs face challenges related to their immunogenicity, effectiveness, and safety. To ease the burden of IBD and other severe diseases, biosimilars have emerged as a cost-effective alternative to an originator product. According to the current knowledge, biosimilars of IFX and ADL in IBD patients are shown to be as safe and effective as their originators. The future of biosimilars, in general, is promising due to the potential of making the health care system more sustainable. However, their use is accompanied by misconceptions regarding their effectiveness and safety, as well as by controversy regarding their interchangeability. Hence, until a scientific consensus is achieved, scientific data on the long-term effectiveness and safety of biosimilars are needed. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
11. Structural and Functional Analysis of CEX Fractions Collected from a Novel Avastin ® Biosimilar Candidate and Its Innovator: A Comparative Study.
- Author
-
Gurel, Busra, Berksoz, Melike, Capkin, Eda, Parlar, Ayhan, Pala, Meltem Corbacioglu, Ozkan, Aylin, Capan, Yılmaz, Daglikoca, Duygu Emine, and Yuce, Meral
- Subjects
- *
BEVACIZUMAB , *SURFACE plasmon resonance , *FUNCTIONAL analysis , *SIGNAL peptides , *POST-translational modification , *PEPTIDES , *MONOCLONAL antibodies , *FRACTIONS - Abstract
Avastin® is a humanized recombinant monoclonal antibody used to treat cancer by targeting VEGF-A to inhibit angiogenesis. SIMAB054, an Avastin® biosimilar candidate developed in this study, showed a different charge variant profile than its innovator. Thus, it is fractionated into acidic, main, and basic isoforms and collected physically by Cation Exchange Chromatography (CEX) for a comprehensive structural and functional analysis. The innovator product, fractionated into the same species and collected by the same method, is used as a reference for comparative analysis. Ultra-Performance Liquid Chromatography (UPLC) ESI-QToF was used to analyze the modifications leading to charge heterogeneities at intact protein and peptide levels. The C-terminal lysine clipping and glycosylation profiles of the samples were monitored by intact mAb analysis. The post-translational modifications, including oxidation, deamidation, and N-terminal pyroglutamic acid formation, were determined by peptide mapping analysis in the selected signal peptides. The relative binding affinities of the fractionated charge isoforms against the antigen, VEGF-A, and the neonatal receptor, FcRn, were revealed by Surface Plasmon Resonance (SPR) studies. The results show that all CEX fractions from the innovator product and the SIMAB054 shared the same structural variants, albeit in different ratios. Common glycoforms and post-translational modifications were the same, but at different percentages for some samples. The dissimilarities were mostly originating from the presence of extra C-term Lysin residues, which are prone to enzymatic degradation in the body, and thus they were previously assessed as clinically irrelevant. Another critical finding was the presence of different glyco proteoforms in different charge species, such as increased galactosylation in the acidic and afucosylation in the basic species. SPR characterization of the isolated charge variants further confirmed that basic species found in the CEX analyses of the biosimilar candidate were also present in the innovator product, although at lower amounts. The charge variants' in vitro antigen- and neonatal receptor-binding activities varied amongst the samples, which could be further investigated in vivo with a larger sample set to reveal the impact on the pharmacokinetics of drug candidates. Minor structural differences may explain antigen-binding differences in the isolated charge variants, which is a key parameter in a comparability exercise. Consequently, such a biosimilar candidate may not comply with high regulatory standards unless the binding differences observed are justified and demonstrated not to have any clinical impact. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
12. Biosimilars in Oncology: Latest Trends and Regulatory Status
- Author
-
Deeksha Joshi, Rubiya Khursheed, Saurabh Gupta, Diksha Wadhwa, Thakur Gurjeet Singh, Sumit Sharma, Sejal Porwal, Swati Gauniyal, Sukriti Vishwas, Sanjay Goyal, Gaurav Gupta, Rajaraman D. Eri, Kylie A. Williams, Kamal Dua, and Sachin Kumar Singh
- Subjects
oncology ,biologics ,biosimilars ,regulatory framework ,traceability ,Pharmacy and materia medica ,RS1-441 - Abstract
Biologic-based medicines are used to treat a variety of diseases and account for around one-quarter of the worldwide pharmaceutical market. The use of biologic medications among cancer patients has resulted in substantial advancements in cancer treatment and supportive care. Biosimilar medications (or biosimilars) are very similar to the reference biologic drugs, although they are not identical. As patent protection for some of the most extensively used biologics begins to expire, biosimilars have the potential to enhance access and provide lower-cost options for cancer treatment. Initially, regulatory guidelines were set up in Europe in 2003, and the first biosimilar was approved in 2006 in Europe. Many countries, including the United States of America (USA), Canada, and Japan, have adopted Europe’s worldwide regulatory framework. The use of numerous biosimilars in the treatment and supportive care of cancer has been approved and, indeed, the count is set to climb in the future around the world. However, there are many challenges associated with biosimilars, such as cost, immunogenicity, lack of awareness, extrapolation of indications, and interchangeability. The purpose of this review is to provide an insight into biosimilars, which include various options available for oncology, and the associated adverse events. We compare the regulatory guidelines for biosimilars across the world, and also present the latest trends and challenges in medical oncology both now and in the future, which will assist healthcare professionals, payers, and patients in making informed decisions, increasing the acceptance of biosimilars in clinical practice, increasing accessibility, and speeding up the health and economic benefits associated with biosimilars.
- Published
- 2022
- Full Text
- View/download PDF
13. Structural and Functional Analysis of CEX Fractions Collected from a Novel Avastin® Biosimilar Candidate and Its Innovator: A Comparative Study
- Author
-
Busra Gurel, Melike Berksoz, Eda Capkin, Ayhan Parlar, Meltem Corbacioglu Pala, Aylin Ozkan, Yılmaz Capan, Duygu Emine Daglikoca, and Meral Yuce
- Subjects
biosimilars ,monoclonal antibodies ,avastin ,bevacizumab ,cation exchange chromatography ,charge variants ,Pharmacy and materia medica ,RS1-441 - Abstract
Avastin® is a humanized recombinant monoclonal antibody used to treat cancer by targeting VEGF-A to inhibit angiogenesis. SIMAB054, an Avastin® biosimilar candidate developed in this study, showed a different charge variant profile than its innovator. Thus, it is fractionated into acidic, main, and basic isoforms and collected physically by Cation Exchange Chromatography (CEX) for a comprehensive structural and functional analysis. The innovator product, fractionated into the same species and collected by the same method, is used as a reference for comparative analysis. Ultra-Performance Liquid Chromatography (UPLC) ESI-QToF was used to analyze the modifications leading to charge heterogeneities at intact protein and peptide levels. The C-terminal lysine clipping and glycosylation profiles of the samples were monitored by intact mAb analysis. The post-translational modifications, including oxidation, deamidation, and N-terminal pyroglutamic acid formation, were determined by peptide mapping analysis in the selected signal peptides. The relative binding affinities of the fractionated charge isoforms against the antigen, VEGF-A, and the neonatal receptor, FcRn, were revealed by Surface Plasmon Resonance (SPR) studies. The results show that all CEX fractions from the innovator product and the SIMAB054 shared the same structural variants, albeit in different ratios. Common glycoforms and post-translational modifications were the same, but at different percentages for some samples. The dissimilarities were mostly originating from the presence of extra C-term Lysin residues, which are prone to enzymatic degradation in the body, and thus they were previously assessed as clinically irrelevant. Another critical finding was the presence of different glyco proteoforms in different charge species, such as increased galactosylation in the acidic and afucosylation in the basic species. SPR characterization of the isolated charge variants further confirmed that basic species found in the CEX analyses of the biosimilar candidate were also present in the innovator product, although at lower amounts. The charge variants’ in vitro antigen- and neonatal receptor-binding activities varied amongst the samples, which could be further investigated in vivo with a larger sample set to reveal the impact on the pharmacokinetics of drug candidates. Minor structural differences may explain antigen-binding differences in the isolated charge variants, which is a key parameter in a comparability exercise. Consequently, such a biosimilar candidate may not comply with high regulatory standards unless the binding differences observed are justified and demonstrated not to have any clinical impact.
- Published
- 2022
- Full Text
- View/download PDF
14. Purification Process of a Recombinant Human Follicle Stimulating Hormone Biosimilar (Primapur®) to Yield a Pharmaceutical Product with High Batch-to-Batch Consistency
- Author
-
Maria Sinegubova, Ivan Vorobiev, Anatoly Klishin, Dmitry Eremin, Nadezhda Orlova, Natalya Orlova, and Mikhail Polzikov
- Subjects
biopharmaceuticals ,biosimilars ,recombinant human follicle stimulating hormone (r-hFSH) ,follitropin alpha ,downstream ,immunoaffinity chromatography ,Pharmacy and materia medica ,RS1-441 - Abstract
Recombinant human follicle stimulating hormone (r-hFSH) is widely used for infertility treatment and is subject to the development of biosimilars. There are different purification strategies that can yield r-hFSH of pharmaceutical quality from Chinese hamster ovary cell culture broth. We developed a purification process for r-hFSH centered on immunoaffinity chromatography with single-domain recombinant camelid antibodies. The resulting downstream process is simple and devoid of ultrafiltration operations. Studies on chromatography resin resource and ligand leakage showed that the immunoaffinity matrix employed was suitable for industrial use and stable for at least 40 full chromatography cycles, and the leaked single-domain antibody ligand was completely removed by subsequent purification steps. All chromatography resins employed withstood the same 40 cycles of use without significant changes in separation efficiency and product binding capacity. The resulting industrial purification process yielded batches of r-hFSH with consistent levels of purity and bioactivity.
- Published
- 2022
- Full Text
- View/download PDF
15. Uptake of Trastuzumab Biosimilars for the Treatment of HER2-Positive Breast Cancer: A Real-World Experience from a Cancer Center
- Author
-
Michela Piezzo, Roberta D’Aniello, Ilaria Avallone, Bruno Barba, Daniela Cianniello, Stefania Cocco, Antonio D’Avino, Germira Di Gioia, Vincenzo Di Lauro, Giuseppina Fusco, Raffaele Piscitelli, Claudia von Arx, Michelino De Laurentiis, and Piera Maiolino
- Subjects
breast cancer ,trastuzumab ,biosimilars ,HER2 ,Pharmacy and materia medica ,RS1-441 - Abstract
Background: The introduction of trastuzumab biosimilars in clinical practice plays an important role in promoting the sustainability of healthcare systems. By contrast, the switching process can be challenging to the clinics. This survey describes the switching process at a National Cancer Institute over a period of 2 years. Methods: Data regarding all trastuzumab-based regimens for breast cancer (BC) from 1 January 2019 and 31 December 2020 were extracted from both adverse drug reactions (ADRs) reporting systems and electronic systems involved in inventory management, prescribing, dispensing, and administration. Both patients under monotherapy and combination treatment regimens were included. There were no exclusion criteria. Results and Conclusions: Overall 354 patients received at least one trastuzumab-based regimen for a total of 493 lines of treatment and 5769 administrations. Biosimilar were used in 34.3% of trastuzumab-based treatments. No differences between biosimilars and reference drug have been observed in terms of ADRs. The effective cost-saving of the first 2 years is greater than EUR 800,000 and it is estimated to increase over time.
- Published
- 2021
- Full Text
- View/download PDF
16. The Biosimilar Landscape: An Overview of Regulatory Approvals by the EMA and FDA
- Author
-
Ioana Gherghescu and M. Begoña Delgado-Charro
- Subjects
biosimilars ,FDA ,EMA ,adalimumab ,Humira ,biosimilarity ,Pharmacy and materia medica ,RS1-441 - Abstract
Biosimilar medicines expand the biotherapeutic market and improve patient access. This work looked into the landscape of the European and US biosimilar products, their regulatory authorization, market availability, and clinical evaluation undergone prior to the regulatory approval. European Medicines Agency (EMEA, currently EMA) and Food and Drug Administration (FDA) repositories were searched to identify all biosimilar medicines approved before December 2019. Adalimumab biosimilars, and particularly their clinical evaluations, were used as a case study. In the past 13 years, the EMA has received 65 marketing authorization applications for biosimilar medicines with 55 approved biosimilars available in the EU market. Since the first biosimilar approval in 2015, the FDA has granted 26 approvals for biosimilars with only 11 being currently on the US market. Five adalimumab biosimilars have been approved in the EU and commercialized as eight different medicines through duplicate marketing authorizations. Whilst three of these are FDA-approved, the first adalimumab biosimilar will not be marketed in the US until 2023 due to Humira’s exclusivity period. The EU biosimilar market has developed faster than its US counterpart, as the latter is probably challenged by a series of patents and exclusivity periods protecting the bio-originator medicines, an issue addressed by the US’s latest ‘Biosimilar Action Plan’.
- Published
- 2020
- Full Text
- View/download PDF
17. Purification Process of a Recombinant Human Follicle Stimulating Hormone Biosimilar (Primapur
- Author
-
Maria, Sinegubova, Ivan, Vorobiev, Anatoly, Klishin, Dmitry, Eremin, Nadezhda, Orlova, Natalya, Orlova, and Mikhail, Polzikov
- Subjects
follitropin alpha ,dynamic binding capacity (DBC) ,batch-to-batch consistency ,biosimilars ,recombinant human follicle stimulating hormone (r-hFSH) ,biopharmaceuticals ,downstream ,immunoaffinity chromatography ,Article - Abstract
Recombinant human follicle stimulating hormone (r-hFSH) is widely used for infertility treatment and is subject to the development of biosimilars. There are different purification strategies that can yield r-hFSH of pharmaceutical quality from Chinese hamster ovary cell culture broth. We developed a purification process for r-hFSH centered on immunoaffinity chromatography with single-domain recombinant camelid antibodies. The resulting downstream process is simple and devoid of ultrafiltration operations. Studies on chromatography resin resource and ligand leakage showed that the immunoaffinity matrix employed was suitable for industrial use and stable for at least 40 full chromatography cycles, and the leaked single-domain antibody ligand was completely removed by subsequent purification steps. All chromatography resins employed withstood the same 40 cycles of use without significant changes in separation efficiency and product binding capacity. The resulting industrial purification process yielded batches of r-hFSH with consistent levels of purity and bioactivity.
- Published
- 2021
18. Concepts and Challenges of Biosimilars in Breast Cancer: The Emergence of Trastuzumab Biosimilars
- Author
-
Alina Uifălean, Maria Ilieş, Raul Nicoară, Lucia Maria Rus, Simona Codruţa Hegheş, and Cristina-Adela Iuga
- Subjects
biosimilars ,breast cancer ,HER2-positive ,trastuzumab ,biologic medicines ,comparability exercise ,interchangeability ,substitution ,Pharmacy and materia medica ,RS1-441 - Abstract
With the development of anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibodies, trastuzumab-based therapy has become the standard of care among patients with early or advanced HER2-positive breast cancer. However, real-world data have shown that up to a half of patients do not receive trastuzumab or any other HER2-targeted agent, mainly due to high treatments costs. The prospect of a more enlarged access to trastuzumab treatment lies in the use of biosimilars, as the European and the US patent of the reference products has or will soon expire. Biosimilars are biologics highly similar in terms of quality characteristics, biological activity, safety and efficacy to already approved biologics. The biosimilarity of any European Union (EU)-approved biosimilar is guaranteed based on the comprehensive comparability exercise which includes comparative analytical, non-clinical and clinical studies. In the matter of biosimilars’ interchangeability and substitution, the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) have adopted different positions, triggering various discussions on the potential immunogenicity and efficacy in individual patients. As more biosimilars are gaining approval, the present review aims to offer concise information for oncologists and pharmacists about the production, approval, interchangeability, and substitution policies of biosimilars used in breast cancer therapy, with a special focus on trastuzumab.
- Published
- 2018
- Full Text
- View/download PDF
19. Uptake of Trastuzumab Biosimilars for the Treatment of HER2-Positive Breast Cancer: A Real-World Experience from a Cancer Center
- Author
-
Roberta D’Aniello, Piera Maiolino, Vincenzo Di Lauro, Ilaria Avallone, Daniela Cianniello, Germira Di Gioia, Giuseppina Fusco, Michelino De Laurentiis, Stefania Cocco, Antonio D’Avino, Claudia von Arx, Raffaele Piscitelli, Michela Piezzo, and Bruno Barba
- Subjects
Oncology ,medicine.medical_specialty ,Pharmaceutical Science ,Article ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,breast cancer ,Pharmacy and materia medica ,Trastuzumab ,Internal medicine ,HER2 Positive Breast Cancer ,HER2 ,medicine ,biosimilars ,030212 general & internal medicine ,Drug reaction ,business.industry ,Cancer ,Biosimilar ,Reference drug ,medicine.disease ,RS1-441 ,Regimen ,trastuzumab ,030220 oncology & carcinogenesis ,business ,medicine.drug - Abstract
Background: The introduction of trastuzumab biosimilars in clinical practice plays an important role in promoting the sustainability of healthcare systems. By contrast, the switching process can be challenging to the clinics. This survey describes the switching process at a National Cancer Institute over a period of 2 years. Methods: Data regarding all trastuzumab-based regimens for breast cancer (BC) from 1 January 2019 and 31 December 2020 were extracted from both adverse drug reactions (ADRs) reporting systems and electronic systems involved in inventory management, prescribing, dispensing, and administration. Both patients under monotherapy and combination treatment regimens were included. There were no exclusion criteria. Results and Conclusions: Overall 354 patients received at least one trastuzumab-based regimen for a total of 493 lines of treatment and 5769 administrations. Biosimilar were used in 34.3% of trastuzumab-based treatments. No differences between biosimilars and reference drug have been observed in terms of ADRs. The effective cost-saving of the first 2 years is greater than EUR 800,000 and it is estimated to increase over time.
- Published
- 2021
20. Purification Process of a Recombinant Human Follicle Stimulating Hormone Biosimilar (Primapur ®) to Yield a Pharmaceutical Product with High Batch-to-Batch Consistency.
- Author
-
Sinegubova, Maria, Vorobiev, Ivan, Klishin, Anatoly, Eremin, Dmitry, Orlova, Nadezhda, Orlova, Natalya, and Polzikov, Mikhail
- Subjects
- *
AFFINITY chromatography , *CHO cell , *IMMUNOAFFINITY chromatography , *RECOMBINANT antibodies , *CELL culture - Abstract
Recombinant human follicle stimulating hormone (r-hFSH) is widely used for infertility treatment and is subject to the development of biosimilars. There are different purification strategies that can yield r-hFSH of pharmaceutical quality from Chinese hamster ovary cell culture broth. We developed a purification process for r-hFSH centered on immunoaffinity chromatography with single-domain recombinant camelid antibodies. The resulting downstream process is simple and devoid of ultrafiltration operations. Studies on chromatography resin resource and ligand leakage showed that the immunoaffinity matrix employed was suitable for industrial use and stable for at least 40 full chromatography cycles, and the leaked single-domain antibody ligand was completely removed by subsequent purification steps. All chromatography resins employed withstood the same 40 cycles of use without significant changes in separation efficiency and product binding capacity. The resulting industrial purification process yielded batches of r-hFSH with consistent levels of purity and bioactivity. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
21. Quantitative N- Glycan Profiling of Therapeutic Monoclonal Antibodies Performed by Middle-Up Level HILIC-HRMS Analysis.
- Author
-
Duivelshof, Bastiaan L., Denorme, Steffy, Sandra, Koen, Liu, Xiaoxiao, Beck, Alain, Lauber, Matthew A., Guillarme, Davy, and D'Atri, Valentina
- Subjects
- *
GLYCANS , *ATEZOLIZUMAB , *MONOCLONAL antibodies , *MOIETIES (Chemistry) , *GLYCOSYLATION , *BIOSIMILARS , *ADALIMUMAB - Abstract
The identification and accurate quantitation of the various glycoforms contained in therapeutic monoclonal antibodies (mAbs) is one of the main analytical needs in the biopharmaceutical industry, and glycosylation represents a crucial critical quality attribute (CQA) that needs to be addressed. Currently, the reference method for performing such identification/quantitation consists of the release of the N-glycan moieties from the mAb, their labelling with a specific dye (e.g., 2-AB or RFMS) and their analysis by HILIC-FLD or HILIC-MS. In this contribution, the potential of a new cost- and time-effective analytical approach performed at the protein subunit level (middle-up) was investigated for quantitative purposes and compared with the reference methods. The robustness of the approach was first demonstrated by performing the relative quantification of the glycoforms related to a well characterized mAb, namely adalimumab. Then, the workflow was applied to various glyco-engineered mAb products (i.e., obinutuzumab, benralizumab and atezolizumab). Finally, the glycosylation pattern of infliximab (Remicade®) was assessed and compared to two of its commercially available biosimilars (Remsima® and Inflectra®). The middle-up analysis proved to provide accurate quantitation results and has the added potential to be used as multi-attribute monitoring method. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
22. Uptake of Trastuzumab Biosimilars for the Treatment of HER2-Positive Breast Cancer: A Real-World Experience from a Cancer Center.
- Author
-
Piezzo, Michela, D'Aniello, Roberta, Avallone, Ilaria, Barba, Bruno, Cianniello, Daniela, Cocco, Stefania, D'Avino, Antonio, Di Gioia, Germira, Di Lauro, Vincenzo, Fusco, Giuseppina, Piscitelli, Raffaele, von Arx, Claudia, De Laurentiis, Michelino, Maiolino, Piera, Minghetti, Paola, Musazzi, Umberto, and Rocco, Paolo
- Subjects
- *
HER2 positive breast cancer , *DRUG side effects , *TRASTUZUMAB , *BIOSIMILARS , *BREAST cancer - Abstract
Background: The introduction of trastuzumab biosimilars in clinical practice plays an important role in promoting the sustainability of healthcare systems. By contrast, the switching process can be challenging to the clinics. This survey describes the switching process at a National Cancer Institute over a period of 2 years. Methods: Data regarding all trastuzumab-based regimens for breast cancer (BC) from 1 January 2019 and 31 December 2020 were extracted from both adverse drug reactions (ADRs) reporting systems and electronic systems involved in inventory management, prescribing, dispensing, and administration. Both patients under monotherapy and combination treatment regimens were included. There were no exclusion criteria. Results and Conclusions: Overall 354 patients received at least one trastuzumab-based regimen for a total of 493 lines of treatment and 5769 administrations. Biosimilar were used in 34.3% of trastuzumab-based treatments. No differences between biosimilars and reference drug have been observed in terms of ADRs. The effective cost-saving of the first 2 years is greater than EUR 800,000 and it is estimated to increase over time. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
23. Concepts and Challenges of Biosimilars in Breast Cancer: The Emergence of Trastuzumab Biosimilars
- Author
-
Cristina Adela Iuga, Raul Nicoară, Maria Ilies, Simona Codruţa Hegheş, Alina Uifălean, and Lucia Maria Rus
- Subjects
0301 basic medicine ,medicine.medical_specialty ,Standard of care ,comparability exercise ,Pharmaceutical Science ,lcsh:RS1-441 ,Review ,Interchangeability ,Food and drug administration ,biologic medicines ,lcsh:Pharmacy and materia medica ,03 medical and health sciences ,0302 clinical medicine ,Breast cancer ,breast cancer ,Trastuzumab ,substitution ,medicine ,media_common.cataloged_instance ,biosimilars ,European union ,Intensive care medicine ,Quality characteristics ,skin and connective tissue diseases ,media_common ,business.industry ,Biosimilar ,medicine.disease ,HER2-positive ,trastuzumab ,030104 developmental biology ,030220 oncology & carcinogenesis ,business ,interchangeability ,medicine.drug - Abstract
With the development of anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibodies, trastuzumab-based therapy has become the standard of care among patients with early or advanced HER2-positive breast cancer. However, real-world data have shown that up to a half of patients do not receive trastuzumab or any other HER2-targeted agent, mainly due to high treatments costs. The prospect of a more enlarged access to trastuzumab treatment lies in the use of biosimilars, as the European and the US patent of the reference products has or will soon expire. Biosimilars are biologics highly similar in terms of quality characteristics, biological activity, safety and efficacy to already approved biologics. The biosimilarity of any European Union (EU)-approved biosimilar is guaranteed based on the comprehensive comparability exercise which includes comparative analytical, non-clinical and clinical studies. In the matter of biosimilars’ interchangeability and substitution, the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) have adopted different positions, triggering various discussions on the potential immunogenicity and efficacy in individual patients. As more biosimilars are gaining approval, the present review aims to offer concise information for oncologists and pharmacists about the production, approval, interchangeability, and substitution policies of biosimilars used in breast cancer therapy, with a special focus on trastuzumab.
- Published
- 2018
24. The Biosimilar Landscape: An Overview of Regulatory Approvals by the EMA and FDA.
- Author
-
Gherghescu, Ioana and Delgado-Charro, M. Begoña
- Subjects
- *
REGULATORY approval , *ADALIMUMAB , *BIOSIMILARS , *SELF-efficacy - Abstract
Biosimilar medicines expand the biotherapeutic market and improve patient access. This work looked into the landscape of the European and US biosimilar products, their regulatory authorization, market availability, and clinical evaluation undergone prior to the regulatory approval. European Medicines Agency (EMEA, currently EMA) and Food and Drug Administration (FDA) repositories were searched to identify all biosimilar medicines approved before December 2019. Adalimumab biosimilars, and particularly their clinical evaluations, were used as a case study. In the past 13 years, the EMA has received 65 marketing authorization applications for biosimilar medicines with 55 approved biosimilars available in the EU market. Since the first biosimilar approval in 2015, the FDA has granted 26 approvals for biosimilars with only 11 being currently on the US market. Five adalimumab biosimilars have been approved in the EU and commercialized as eight different medicines through duplicate marketing authorizations. Whilst three of these are FDA-approved, the first adalimumab biosimilar will not be marketed in the US until 2023 due to Humira's exclusivity period. The EU biosimilar market has developed faster than its US counterpart, as the latter is probably challenged by a series of patents and exclusivity periods protecting the bio-originator medicines, an issue addressed by the US's latest 'Biosimilar Action Plan'. [ABSTRACT FROM AUTHOR]
- Published
- 2021
- Full Text
- View/download PDF
25. The Biosimilar Landscape: An Overview of Regulatory Approvals by the EMA and FDA.
- Author
-
Gherghescu I and Delgado-Charro MB
- Abstract
Biosimilar medicines expand the biotherapeutic market and improve patient access. This work looked into the landscape of the European and US biosimilar products, their regulatory authorization, market availability, and clinical evaluation undergone prior to the regulatory approval. European Medicines Agency (EMEA, currently EMA) and Food and Drug Administration (FDA) repositories were searched to identify all biosimilar medicines approved before December 2019. Adalimumab biosimilars, and particularly their clinical evaluations, were used as a case study. In the past 13 years, the EMA has received 65 marketing authorization applications for biosimilar medicines with 55 approved biosimilars available in the EU market. Since the first biosimilar approval in 2015, the FDA has granted 26 approvals for biosimilars with only 11 being currently on the US market. Five adalimumab biosimilars have been approved in the EU and commercialized as eight different medicines through duplicate marketing authorizations. Whilst three of these are FDA-approved, the first adalimumab biosimilar will not be marketed in the US until 2023 due to Humira's exclusivity period. The EU biosimilar market has developed faster than its US counterpart, as the latter is probably challenged by a series of patents and exclusivity periods protecting the bio-originator medicines, an issue addressed by the US's latest 'Biosimilar Action Plan'.
- Published
- 2020
- Full Text
- View/download PDF
26. Concepts and Challenges of Biosimilars in Breast Cancer: The Emergence of Trastuzumab Biosimilars.
- Author
-
Uifălean A, Ilieş M, Nicoară R, Rus LM, Hegheş SC, and Iuga CA
- Abstract
With the development of anti-human epidermal growth factor receptor 2 (HER2) monoclonal antibodies, trastuzumab-based therapy has become the standard of care among patients with early or advanced HER2-positive breast cancer. However, real-world data have shown that up to a half of patients do not receive trastuzumab or any other HER2-targeted agent, mainly due to high treatments costs. The prospect of a more enlarged access to trastuzumab treatment lies in the use of biosimilars, as the European and the US patent of the reference products has or will soon expire. Biosimilars are biologics highly similar in terms of quality characteristics, biological activity, safety and efficacy to already approved biologics. The biosimilarity of any European Union (EU)-approved biosimilar is guaranteed based on the comprehensive comparability exercise which includes comparative analytical, non-clinical and clinical studies. In the matter of biosimilars' interchangeability and substitution, the European Medicines Agency (EMA) and US Food and Drug Administration (FDA) have adopted different positions, triggering various discussions on the potential immunogenicity and efficacy in individual patients. As more biosimilars are gaining approval, the present review aims to offer concise information for oncologists and pharmacists about the production, approval, interchangeability, and substitution policies of biosimilars used in breast cancer therapy, with a special focus on trastuzumab.
- Published
- 2018
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.