Pub Date : 2024-07-01Epub Date: 2024-05-19DOI: 10.1080/14712598.2024.2354902
Viktoria Moschetti, Susanne Buschke, Julia Bertulis, Kathrin Hohl, Dorothy McCabe
Objective: VOLTAIRE-HCLF compared the relative bioavailability of citrate-free high-concentration and reference formulations of the biosimilar adalimumab-adbm (Cyltezo®), including pharmacokinetic (PK) profiles, immunogenicity, and safety profiles in healthy volunteers.
Methods: Healthy volunteers (N = 200) aged 18-55 years and with body mass index of 18.5-29.9 kg/m2 and no prior exposure to adalimumab were randomized in a 1:1 ratio to receive a single subcutaneous injection of either adalimumab-adbm 40 mg/0.4 mL (high-concentration formulation) or 40 mg/0.8 mL (reference formulation). Participants completed 13 follow-up visits over 57 days, followed by a safety follow-up period of up to 70 days.
Results: The main PK parameters were similar for the high-concentration and reference groups. For all primary endpoints, the geometric mean ratios and 90% confidence intervals of AUC0-1344, AUC0-∞, and Cmax for both groups were entirely within the standard 80-125% bioequivalence acceptance range at 101.88% (93.31-111.23%), 105.38% (95.06-116.81%), and 91.29% (84.38-98.76%), respectively. There were no differences in the proportion of anti-drug antibody-positive participants or in the distribution of anti-drug antibody titers between the two formulations at any time point after drug dosing. Participants who were given the high-concentration formulation of adalimumab-adbm experienced a lower incidence of adverse events and local reactions than those who were given the reference formulation.
Conclusions: Overall, the high-concentration and reference adalimumab-adbm formulations had highly similar PK and immunogenicity profiles and were safe and well tolerated.
{"title":"Relative bioavailability, immunogenicity, and safety of two adalimumab-adbm formulations in healthy volunteers: a double-blind, randomized, single-dose, parallel-arm Phase I trial (VOLTAIRE-HCLF).","authors":"Viktoria Moschetti, Susanne Buschke, Julia Bertulis, Kathrin Hohl, Dorothy McCabe","doi":"10.1080/14712598.2024.2354902","DOIUrl":"10.1080/14712598.2024.2354902","url":null,"abstract":"<p><strong>Objective: </strong>VOLTAIRE-HCLF compared the relative bioavailability of citrate-free high-concentration and reference formulations of the biosimilar adalimumab-adbm (Cyltezo®), including pharmacokinetic (PK) profiles, immunogenicity, and safety profiles in healthy volunteers.</p><p><strong>Methods: </strong>Healthy volunteers (<i>N</i> = 200) aged 18-55 years and with body mass index of 18.5-29.9 kg/m<sup>2</sup> and no prior exposure to adalimumab were randomized in a 1:1 ratio to receive a single subcutaneous injection of either adalimumab-adbm 40 mg/0.4 mL (high-concentration formulation) or 40 mg/0.8 mL (reference formulation). Participants completed 13 follow-up visits over 57 days, followed by a safety follow-up period of up to 70 days.</p><p><strong>Results: </strong>The main PK parameters were similar for the high-concentration and reference groups. For all primary endpoints, the geometric mean ratios and 90% confidence intervals of AUC<sub>0-1344</sub>, AUC<sub>0-∞</sub>, and C<sub>max</sub> for both groups were entirely within the standard 80-125% bioequivalence acceptance range at 101.88% (93.31-111.23%), 105.38% (95.06-116.81%), and 91.29% (84.38-98.76%), respectively. There were no differences in the proportion of anti-drug antibody-positive participants or in the distribution of anti-drug antibody titers between the two formulations at any time point after drug dosing. Participants who were given the high-concentration formulation of adalimumab-adbm experienced a lower incidence of adverse events and local reactions than those who were given the reference formulation.</p><p><strong>Conclusions: </strong>Overall, the high-concentration and reference adalimumab-adbm formulations had highly similar PK and immunogenicity profiles and were safe and well tolerated.</p><p><strong>Clinical trial registration: </strong>NCT05203289.</p>","PeriodicalId":12084,"journal":{"name":"Expert Opinion on Biological Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01Epub Date: 2024-07-04DOI: 10.1080/14712598.2024.2376197
Heather Rae Hufnagel, Scott D Tennyson
Purpose: Evaluate the type and quantity of quality information (i.e. Chemistry, Manufacturing, and Control) requested by the US FDA and EMA in queries pertaining to biosimilar applications.
Methods: Numbers/types of queries received following regulatory submissions (FDA/EMA, n = 7/n = 5) for seven biosimilars (PF-filgrastim [Nivestym], PF-rituximab [Ruxience®], PF-trastuzumab [Trazimera®], PF-bevacizumab [Zirabev®], PF-pegfilgrastim [Nyvepria®], PF-adalimumab [Abrilada™/Amsparity®], PF-infliximab [Ixifi]) from a single product portfolio were analyzed considering published regulatory authority (RA) guidance and in relation to sections/subsections of Module 3: Quality from the Common Technical Document regulatory dossier and topics based on keyword assignment.
Results: Queries were most frequently assigned (FDA/EMA %, range) to Drug Substance Manufacture (subsection 3.2.S.2; 21-35%/13-50%), Control of Drug Substance (3.2.S.4; 3-11%/5-17%), Drug Product Pharmaceutical Development (3.2.P.2; 1-12%/1-15%) and Manufacture (3.2.P.3; 17-41%/2-13%), and Analytical Similarity (3.2.R; 4-21%/4-20%). The proportion of Drug Substance and Drug Product queries was significantly different between RAs (n1 = 952, n2 = 468, p-value <0.001; two-sample proportion z-test). Topic assignments included: Control (12-27%/12-28%), Manufacturing (56-72%/34-66%), Stability (1-12%/2-24%), Biosimilarity (5-16%/5-25%), and Container Closure (0-3%/0-9%).
Conclusion: The focus of both RAs on topics related to manufacturing and controls is valuable in understanding expectations for scientific and technical content related to gaining biosimilar approval.
目的:评估美国 FDA 和 EMA 在有关生物仿制药申请的询问中要求提供的质量信息(即化学、制造和控制)的类型和数量:七种生物仿制药(PF-filgrastim [Nivestym]、PF-rituximab [Ruxience®]、PF-trastuzumab [Trazimera®]、PF-bevacizumab [Zirabev®]、对单一产品组合中的 PF-pegfilgrastim [Nyvepria®]、PF-adalimumab [Abrilada™/Amsparity®] 和 PF-infliximab [Ixifi])进行了分析,分析时考虑了已发布的监管机构 (RA) 指南,并与模块 3 的章节/子章节相关:结果:查询最常被分配(FDA/EMA %,范围)到药物物质制造(3.2.S.2 小节;21-35%/13-50%)、药物物质控制(3.2.S.4;3-11%/5-17%)、药物产品药物开发(3.2.P.2;1-12%/1-15%)和制造(3.2.P.3;17-41%/2-13%)以及分析相似性(3.2.R;4-21%/4-20%)。药物物质和药物产品查询的比例在 RA 之间存在显著差异(n1 = 952,n2 = 468,P 值 结论):两个注册中心都将重点放在与生产和控制相关的主题上,这对于了解与获得生物仿制药批准相关的科学和技术内容的期望值很有价值。
{"title":"Industry perspective on regulatory authority (RA) quality reviews of biosimilar applications - an evaluation of RA guidance and expectations for chemical, manufacturing, and controls information through in-depth query analysis.","authors":"Heather Rae Hufnagel, Scott D Tennyson","doi":"10.1080/14712598.2024.2376197","DOIUrl":"10.1080/14712598.2024.2376197","url":null,"abstract":"<p><strong>Purpose: </strong>Evaluate the type and quantity of quality information (i.e. Chemistry, Manufacturing, and Control) requested by the US FDA and EMA in queries pertaining to biosimilar applications.</p><p><strong>Methods: </strong>Numbers/types of queries received following regulatory submissions (FDA/EMA, <i>n</i> = 7/<i>n</i> = 5) for seven biosimilars (PF-filgrastim [Nivestym], PF-rituximab [Ruxience®], PF-trastuzumab [Trazimera®], PF-bevacizumab [Zirabev®], PF-pegfilgrastim [Nyvepria®], PF-adalimumab [Abrilada™/Amsparity®], PF-infliximab [Ixifi]) from a single product portfolio were analyzed considering published regulatory authority (RA) guidance and in relation to sections/subsections of Module 3: Quality from the Common Technical Document regulatory dossier and topics based on keyword assignment.</p><p><strong>Results: </strong>Queries were most frequently assigned (FDA/EMA %, range) to Drug Substance Manufacture (subsection 3.2.S.2; 21-35%/13-50%), Control of Drug Substance (3.2.S.4; 3-11%/5-17%), Drug Product Pharmaceutical Development (3.2.P.2; 1-12%/1-15%) and Manufacture (3.2.P.3; 17-41%/2-13%), and Analytical Similarity (3.2.R; 4-21%/4-20%). The proportion of Drug Substance and Drug Product queries was significantly different between RAs (n1 = 952, n2 = 468, p-value <0.001; two-sample proportion z-test). Topic assignments included: Control (12-27%/12-28%), Manufacturing (56-72%/34-66%), Stability (1-12%/2-24%), Biosimilarity (5-16%/5-25%), and Container Closure (0-3%/0-9%).</p><p><strong>Conclusion: </strong>The focus of both RAs on topics related to manufacturing and controls is valuable in understanding expectations for scientific and technical content related to gaining biosimilar approval.</p>","PeriodicalId":12084,"journal":{"name":"Expert Opinion on Biological Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141497535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01Epub Date: 2024-07-18DOI: 10.1080/14712598.2024.2378090
Gary R Lichtenstein, Arif Soonasra, Mark Latymer, Sheena Singh, Brian G Feagan
Introduction: Infliximab (IFX) biosimilars are available to treat inflammatory bowel disease (IBD), offering cost reductions versus originator IFX in some jurisdictions. However, concerns remain regarding the efficacy and safety of originator-to-biosimilar switching. This systematic literature review evaluated safety and effectiveness of switching between IFX products in patients with IBD, including multiple switchers.
Methods: Embase, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials were searched to capture studies (2012-2022) including patients with IBD who switched between approved IFX products. Effectiveness outcomes: disease activity; disease severity; response to treatment; patient-reported outcomes (PROs). Safety outcomes: incidence and rate of adverse events (AEs); discontinuations due to AEs, failure rate; hospitalizations; surgeries. Immunogenicity outcomes (n, %): anti-drug antibodies; patients receiving concomitant immunomodulatory medication.
Results: Data from 85 publications (81 observational, two randomized controlled trials) were included. Clinical effectiveness outcomes were consistent with the known profile of originator IFX with no difference after switching. There were no unexpected/serious AEs after switching, and rates of AEs were generally consistent with the known profile of IFX.
Conclusions: Most studies reported that clinical, PROs, and safety outcomes for originator-to-biosimilar switching were clinically equivalent to originator responses. Limited data are available regarding multiple switches.
Protocol registration: www.crd.york.ac.uk/prospero identifier is CRD42021289144.
{"title":"Systematic review: effectiveness and safety of switching between originator infliximab and biosimilar infliximab in patients with inflammatory bowel disease.","authors":"Gary R Lichtenstein, Arif Soonasra, Mark Latymer, Sheena Singh, Brian G Feagan","doi":"10.1080/14712598.2024.2378090","DOIUrl":"10.1080/14712598.2024.2378090","url":null,"abstract":"<p><strong>Introduction: </strong>Infliximab (IFX) biosimilars are available to treat inflammatory bowel disease (IBD), offering cost reductions versus originator IFX in some jurisdictions. However, concerns remain regarding the efficacy and safety of originator-to-biosimilar switching. This systematic literature review evaluated safety and effectiveness of switching between IFX products in patients with IBD, including multiple switchers.</p><p><strong>Methods: </strong>Embase, PubMed, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials were searched to capture studies (2012-2022) including patients with IBD who switched between approved IFX products. Effectiveness outcomes: disease activity; disease severity; response to treatment; patient-reported outcomes (PROs). Safety outcomes: incidence and rate of adverse events (AEs); discontinuations due to AEs, failure rate; hospitalizations; surgeries. Immunogenicity outcomes (n, %): anti-drug antibodies; patients receiving concomitant immunomodulatory medication.</p><p><strong>Results: </strong>Data from 85 publications (81 observational, two randomized controlled trials) were included. Clinical effectiveness outcomes were consistent with the known profile of originator IFX with no difference after switching. There were no unexpected/serious AEs after switching, and rates of AEs were generally consistent with the known profile of IFX.</p><p><strong>Conclusions: </strong>Most studies reported that clinical, PROs, and safety outcomes for originator-to-biosimilar switching were clinically equivalent to originator responses. Limited data are available regarding multiple switches.</p><p><strong>Protocol registration: </strong>www.crd.york.ac.uk/prospero identifier is CRD42021289144.</p>","PeriodicalId":12084,"journal":{"name":"Expert Opinion on Biological Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141558386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Background: This study aimed to assess the efficacy and safety of MW031 in Chinese postmenopausal women with osteoporosis.
Patients and methods: In this randomized, double-blind, placebo-controlled, multicenter clinical trial, 448 postmenopausal women with osteoporosis were randomized 3:1 to receive MW031 and placebo for 12 months. The primary efficacy endpoint was the percentage change from baseline in BMD at lumbar spine in month 12. The safety and immunogenicity profiles were also included.
Results: Of 448 randomized patients, 421 completed the study (MW031, n = 322; placebo, n = 99).After 12 months of MW031 treatment, BMD increased by 5.80% at lumbar spine,3.65% at total hip, and 2.93% at femoral neck. The model-adjusted difference was 3.86% (P<0.0001), 2.34% (P<0.0001), and 1.05% (p = 0.08) compared with placebo group, respectively. For the bone turnover markers, serum CTX level in MW031 group decreased to the maximum difference in month 1 (-71.71%, 95% CI: -77.83%, -65.60%, P<0.0001) compared with the placebo group. The safety analysis showed no significant differences in the proportion of patients reporting any adverse events between the two groups.
Conclusion: This study demonstrated that MW031 safely and effectively increased BMD and rapidly decreased the level of bone resorption marker in Chinese postmenopausal women with osteoporosis.
{"title":"Randomized, double-blind, placebo-controlled, multicenter study to evaluate efficacy and safety of the denosumab biosimilar MW031 in Chinese postmenopausal women with osteoporosis.","authors":"Yan Jiang, Yanan Huo, Yufeng Li, Xijian Kong, Bingwu Wang, Feng Liu, Xin Zheng, Yukun Li, Yunfa Yang, Yongsheng Xu, Qingyun Xue, Zhitian Hu, Yanfeng Xiao, Wen Ma, Yinhan Guo, Wei Yu, Weibo Xia","doi":"10.1080/14712598.2024.2352587","DOIUrl":"10.1080/14712598.2024.2352587","url":null,"abstract":"<p><strong>Background: </strong>This study aimed to assess the efficacy and safety of MW031 in Chinese postmenopausal women with osteoporosis.</p><p><strong>Patients and methods: </strong>In this randomized, double-blind, placebo-controlled, multicenter clinical trial, 448 postmenopausal women with osteoporosis were randomized 3:1 to receive MW031 and placebo for 12 months. The primary efficacy endpoint was the percentage change from baseline in BMD at lumbar spine in month 12. The safety and immunogenicity profiles were also included.</p><p><strong>Results: </strong>Of 448 randomized patients, 421 completed the study (MW031, <i>n</i> = 322; placebo, <i>n</i> = 99).After 12 months of MW031 treatment, BMD increased by 5.80% at lumbar spine,3.65% at total hip, and 2.93% at femoral neck. The model-adjusted difference was 3.86% (P<0.0001), 2.34% (P<0.0001), and 1.05% (<i>p</i> = 0.08) compared with placebo group, respectively. For the bone turnover markers, serum CTX level in MW031 group decreased to the maximum difference in month 1 (-71.71%, 95% CI: -77.83%, -65.60%, P<0.0001) compared with the placebo group. The safety analysis showed no significant differences in the proportion of patients reporting any adverse events between the two groups.</p><p><strong>Conclusion: </strong>This study demonstrated that MW031 safely and effectively increased BMD and rapidly decreased the level of bone resorption marker in Chinese postmenopausal women with osteoporosis.</p><p><strong>Trial registration: </strong>NCT05215977 (ClinicalTrials.gov.).</p>","PeriodicalId":12084,"journal":{"name":"Expert Opinion on Biological Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140944357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01Epub Date: 2024-02-22DOI: 10.1080/14712598.2024.2316846
Anhye Kim, Jang Hee Hong, Wonsuk Shin, Hyounggyoon Yoo, Jin-Gyu Jung, Jean-Yves Reginster, SungHyun Kim, YunJu Bae, JeeHye Suh, Sera Kim, EunKyung Lee, Stuart Silverman
Background: This study's objective was to demonstrate pharmacokinetic (PK) similarity and safety of denosumab biosimilar, CT‑P41, and United States-licensed reference denosumab (US-denosumab) in healthy male Asian adults, considering also pharmacodynamic (PD) outcomes.
Research design and methods: This double-blind, two-arm, parallel-group, Phase 1 study randomized (1:1) healthy males to a single (60-mg) subcutaneous dose of CT‑P41 or US-denosumab. Primary endpoints were area under the concentration - time curve (AUC) from time zero to infinity (AUC0-inf), AUC from time zero to the last quantifiable concentration (AUC0-last), and maximum serum concentration (Cmax). PK equivalence was determined if 90% confidence intervals (CIs) for ratios of geometric least-squares means (gLSMs) were within the predefined 80-125% equivalence margin. Secondary PK, PD, safety, and immunogenicity outcomes were also evaluated.
Results: Of 154 participants randomized (76 CT‑P41; 78 US-denosumab), 151 received study drug (74 CT‑P41; 77 US-denosumab). Primary and secondary PK results, PD results, safety, and immunogenicity were comparable between groups. Ninety percent CIs for ratios of gLSMs were within the predefined equivalence margin for AUC0-inf (100.4-114.7), AUC0-last (99.9-114.3), and Cmax (95.2-107.3).
Conclusions: Following a single dose in healthy males, CT‑P41 demonstrated PK equivalence with US-denosumab.
{"title":"A randomized, double-blind, single-dose, phase 1 study comparing the pharmacokinetics, pharmacodynamics, safety, and immunogenicity of denosumab biosimilar CT‑P41 and reference denosumab in healthy males.","authors":"Anhye Kim, Jang Hee Hong, Wonsuk Shin, Hyounggyoon Yoo, Jin-Gyu Jung, Jean-Yves Reginster, SungHyun Kim, YunJu Bae, JeeHye Suh, Sera Kim, EunKyung Lee, Stuart Silverman","doi":"10.1080/14712598.2024.2316846","DOIUrl":"10.1080/14712598.2024.2316846","url":null,"abstract":"<p><strong>Background: </strong>This study's objective was to demonstrate pharmacokinetic (PK) similarity and safety of denosumab biosimilar, CT‑P41, and United States-licensed reference denosumab (US-denosumab) in healthy male Asian adults, considering also pharmacodynamic (PD) outcomes.</p><p><strong>Research design and methods: </strong>This double-blind, two-arm, parallel-group, Phase 1 study randomized (1:1) healthy males to a single (60-mg) subcutaneous dose of CT‑P41 or US-denosumab. Primary endpoints were area under the concentration - time curve (AUC) from time zero to infinity (AUC<sub>0-inf</sub>), AUC from time zero to the last quantifiable concentration (AUC<sub>0-last</sub>), and maximum serum concentration (C<sub>max</sub>). PK equivalence was determined if 90% confidence intervals (CIs) for ratios of geometric least-squares means (gLSMs) were within the predefined 80-125% equivalence margin. Secondary PK, PD, safety, and immunogenicity outcomes were also evaluated.</p><p><strong>Results: </strong>Of 154 participants randomized (76 CT‑P41; 78 US-denosumab), 151 received study drug (74 CT‑P41; 77 US-denosumab). Primary and secondary PK results, PD results, safety, and immunogenicity were comparable between groups. Ninety percent CIs for ratios of gLSMs were within the predefined equivalence margin for AUC<sub>0-inf</sub> (100.4-114.7), AUC<sub>0-last</sub> (99.9-114.3), and C<sub>max</sub> (95.2-107.3).</p><p><strong>Conclusions: </strong>Following a single dose in healthy males, CT‑P41 demonstrated PK equivalence with US-denosumab.</p><p><strong>Trial registration: </strong>ClinicalTrials.gov: NCT06037395.</p>","PeriodicalId":12084,"journal":{"name":"Expert Opinion on Biological Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139722193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-07-01Epub Date: 2024-06-06DOI: 10.1080/14712598.2024.2363229
Isabel Río-Álvarez, Encarnación Cruz-Martos
Introduction: After 17 years on the market, biosimilar medicines have contributed significantly to the sustainability of healthcare in Spain, providing cost-effective treatment options and savings of more than €1 billion by 2022 alone. To fully exploit this potential and meet the European pharmaceutical strategy's objectives of increased access and a resilient supply chain, Member States need to optimize their biosimilars policies.
Areas covered: We conducted an exhaustive review of biosimilar medicines in Spain, first describing their regulatory framework. Biosimilar policies at both national and regional level have been collected and updated figures on the biosimilars market are provided based on official data. Knowledge and acceptance of biosimilar medicines among patients and medical societies based on biosimilar positioning documents is reviewed. National evidence on the contribution of biosimilars to savings and sustainability is also included in this study.
Expert opinion: In Spain, there is a need to further build confidence in biosimilars, develop a strong national biosimilars policy and address regional variability, improve public procurement and adapt clinical practice guidelines following the commercialization of biosimilars. By implementing a holistic and evidence-based policy, Spain can fully exploit the benefits of biosimilar medicines and ensure better and equitable access across the healthcare system.
{"title":"Overview of biosimilar medicines in Spain: market dynamics, policies, evidence-based insights and avenues for a sustainable market.","authors":"Isabel Río-Álvarez, Encarnación Cruz-Martos","doi":"10.1080/14712598.2024.2363229","DOIUrl":"10.1080/14712598.2024.2363229","url":null,"abstract":"<p><strong>Introduction: </strong>After 17 years on the market, biosimilar medicines have contributed significantly to the sustainability of healthcare in Spain, providing cost-effective treatment options and savings of more than €1 billion by 2022 alone. To fully exploit this potential and meet the European pharmaceutical strategy's objectives of increased access and a resilient supply chain, Member States need to optimize their biosimilars policies.</p><p><strong>Areas covered: </strong>We conducted an exhaustive review of biosimilar medicines in Spain, first describing their regulatory framework. Biosimilar policies at both national and regional level have been collected and updated figures on the biosimilars market are provided based on official data. Knowledge and acceptance of biosimilar medicines among patients and medical societies based on biosimilar positioning documents is reviewed. National evidence on the contribution of biosimilars to savings and sustainability is also included in this study.</p><p><strong>Expert opinion: </strong>In Spain, there is a need to further build confidence in biosimilars, develop a strong national biosimilars policy and address regional variability, improve public procurement and adapt clinical practice guidelines following the commercialization of biosimilars. By implementing a holistic and evidence-based policy, Spain can fully exploit the benefits of biosimilar medicines and ensure better and equitable access across the healthcare system.</p>","PeriodicalId":12084,"journal":{"name":"Expert Opinion on Biological Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141261726","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-06-29DOI: 10.1080/14712598.2024.2371034
Charlotte U Zajc, Elise Sylvander, Manfred Lehner, Michael W Traxlmayr
Introduction: CAR T cells have generated great excitement due to their remarkable clinical response rates in selected hematologic malignancies. However, these engineered immune cells are living drugs which are hard to control after administration.
Areas covered: We discuss small molecule-regulated switch systems which can potentially be used to control CAR T cell function within the patient, as well as the most important obstacles in the CAR T cell field, which might be overcome with those switch systems.
Expert opinion: There is an urgent need to develop advanced switch systems. Once available, we expect that they will open up new avenues for future CAR T cell generations.
导言:CAR T 细胞对某些血液系统恶性肿瘤的临床反应率非常显著,因此引起了极大的关注。然而,这些工程免疫细胞是活体药物,用药后很难控制:我们讨论了有可能用于控制患者体内 CAR T 细胞功能的小分子调控开关系统,以及 CAR T 细胞领域最重要的障碍,这些障碍可能通过这些开关系统得以克服:我们迫切需要开发先进的切换系统。一旦问世,我们预计它们将为未来的 CAR T 细胞世代开辟新的途径。
{"title":"Small molecule-regulated switches to provide functional control of CAR T cells within the patient.","authors":"Charlotte U Zajc, Elise Sylvander, Manfred Lehner, Michael W Traxlmayr","doi":"10.1080/14712598.2024.2371034","DOIUrl":"10.1080/14712598.2024.2371034","url":null,"abstract":"<p><strong>Introduction: </strong>CAR T cells have generated great excitement due to their remarkable clinical response rates in selected hematologic malignancies. However, these engineered immune cells are living drugs which are hard to control after administration.</p><p><strong>Areas covered: </strong>We discuss small molecule-regulated switch systems which can potentially be used to control CAR T cell function within the patient, as well as the most important obstacles in the CAR T cell field, which might be overcome with those switch systems.</p><p><strong>Expert opinion: </strong>There is an urgent need to develop advanced switch systems. Once available, we expect that they will open up new avenues for future CAR T cell generations.</p>","PeriodicalId":12084,"journal":{"name":"Expert Opinion on Biological Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-06-19DOI: 10.1080/14712598.2024.2368192
Eden David, Kelly Hawkins, Neda Shokrian, Ester Del Duca, Emma Guttman-Yassky
Introduction: The understanding of atopic dermatitis (AD) pathogenesis has rapidly expanded in recent years, catalyzing the development of new targeted monoclonal antibody treatments for AD.
Areas covered: This review aims to summarize the latest clinical and molecular data about monoclonal antibodies that are in later stages of development for AD, either in Phase 3 trials or in the pharmacopoeia for up to 5 years, highlighting the biologic underpinning of each drug's mechanism of action and the potential modulation of the AD immune profile.
Expert opinion: The therapeutic pipeline of AD treatments is speedily progressing, introducing the potential for a personalized medical approach in the near future. Understanding how targeting pathogenic players in AD modifies disease progression and symptomatology is key in improving therapeutic choices for patients and identifying ideal patient candidates.
{"title":"Monoclonal antibodies for moderate-to-severe atopic dermatitis: a look at phase III and beyond.","authors":"Eden David, Kelly Hawkins, Neda Shokrian, Ester Del Duca, Emma Guttman-Yassky","doi":"10.1080/14712598.2024.2368192","DOIUrl":"10.1080/14712598.2024.2368192","url":null,"abstract":"<p><strong>Introduction: </strong>The understanding of atopic dermatitis (AD) pathogenesis has rapidly expanded in recent years, catalyzing the development of new targeted monoclonal antibody treatments for AD.</p><p><strong>Areas covered: </strong>This review aims to summarize the latest clinical and molecular data about monoclonal antibodies that are in later stages of development for AD, either in Phase 3 trials or in the pharmacopoeia for up to 5 years, highlighting the biologic underpinning of each drug's mechanism of action and the potential modulation of the AD immune profile.</p><p><strong>Expert opinion: </strong>The therapeutic pipeline of AD treatments is speedily progressing, introducing the potential for a personalized medical approach in the near future. Understanding how targeting pathogenic players in AD modifies disease progression and symptomatology is key in improving therapeutic choices for patients and identifying ideal patient candidates.</p>","PeriodicalId":12084,"journal":{"name":"Expert Opinion on Biological Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141418462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-06-01Epub Date: 2024-06-20DOI: 10.1080/14712598.2024.2370397
Shama Shishodia, Nora Haloob, Claire Hopkins
Introduction: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent inflammatory condition with heterogenous underlying endotypes, the most common being type 2 mediated inflammation. Several biologics have been developed to target specific pro-inflammatory cytokines and their receptors with proven efficacy in both quantitative and qualitative outcomes in patients with severe uncontrolled disease. However, there is an ongoing debate on the role of biologics relative to conventional therapies for CRSwNP and their efficacy in patient subgroups with non-polyp type 2 disease.
Areas covered: This review examines the evidence on the efficacy and safety of biologics in CRSwNP, recommendations for their use, and discusses the broader economic factors influencing their application in clinical practice.
Expert opinion: Emerging real-life data demonstrating the variable efficacy of the available biologics for patients with CRSwNP, coupled with the high cost compared to conventional therapies such as surgery, renders biologics to be considered as an add-on therapy in the majority of cases. However, ongoing research into increasing biologic dose intervals and novel therapies targeting alternative pathways may offer a more cost-effective and sustainable option in future.
{"title":"Antibody-based therapeutics for chronic rhinosinusitis with nasal polyps.","authors":"Shama Shishodia, Nora Haloob, Claire Hopkins","doi":"10.1080/14712598.2024.2370397","DOIUrl":"10.1080/14712598.2024.2370397","url":null,"abstract":"<p><strong>Introduction: </strong>Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent inflammatory condition with heterogenous underlying endotypes, the most common being type 2 mediated inflammation. Several biologics have been developed to target specific pro-inflammatory cytokines and their receptors with proven efficacy in both quantitative and qualitative outcomes in patients with severe uncontrolled disease. However, there is an ongoing debate on the role of biologics relative to conventional therapies for CRSwNP and their efficacy in patient subgroups with non-polyp type 2 disease.</p><p><strong>Areas covered: </strong>This review examines the evidence on the efficacy and safety of biologics in CRSwNP, recommendations for their use, and discusses the broader economic factors influencing their application in clinical practice.</p><p><strong>Expert opinion: </strong>Emerging real-life data demonstrating the variable efficacy of the available biologics for patients with CRSwNP, coupled with the high cost compared to conventional therapies such as surgery, renders biologics to be considered as an add-on therapy in the majority of cases. However, ongoing research into increasing biologic dose intervals and novel therapies targeting alternative pathways may offer a more cost-effective and sustainable option in future.</p>","PeriodicalId":12084,"journal":{"name":"Expert Opinion on Biological Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141426617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Introduction: Recombinant viral-based gene therapy products, such as those incorporating adeno-associated viruses (AAVs), fall under the category of genetically modified organisms (GMOs). The European Union (EU) countries and Japan must obtain environmental risk assessment (ERA) approval for the use of GMOs before starting any clinical trials. It has been reported that the development of GMO-containing products in these two regions encounters several regulatory obstacles due to the longer regulatory procedures and document preparation for ERA.
Areas covered: In this article, we comparatively analyzed the ERA document requirements in the EU and Japan for AAV-based recombinant medicinal products to highlight the differences in the context of potential future attempts of convergence. Additionally, we analyzed non-clinical and clinical shedding data requirements, which are key components of ERA reviews in the EU and Japan. Lastly, we compared the containment measures to minimize the spread of GMOs in the environment in the EU and Japan.
Expert opinion: Based on our comparative analysis, we present several policy recommendations of standardizing and simplifying the application materials and procedures for the ERA regulations on GMOs in the EU and Japan in the mid-, and long-term timeframe to achieve global regulatory convergence.
导言:以重组病毒为基础的基因治疗产品,如含有腺相关病毒(AAV)的产品,属于转基因生物(GMO)的范畴。欧盟国家和日本在使用转基因生物进行临床试验之前,必须获得环境风险评估(ERA)批准。据报道,由于ERA的监管程序和文件准备时间较长,在这两个地区开发含有转基因生物的产品会遇到一些监管障碍:在本文中,我们比较分析了欧盟和日本对基于 AAV 的重组药物产品的 ERA 文件要求,以突出在未来可能的趋同尝试中存在的差异。此外,我们还分析了非临床和临床脱落数据要求,这是欧盟和日本 ERA 审查的关键组成部分。最后,我们比较了欧盟和日本为尽量减少转基因生物在环境中扩散而采取的遏制措施:根据我们的比较分析,我们提出了若干政策建议,即在中长期内规范和简化欧盟和日本转基因生物ERA法规的申请材料和程序,以实现全球法规趋同。
{"title":"Comparative analysis of GMO regulatory requirements for AAV vectors in the EU and Japan focusing on the shedding data and containment measures.","authors":"Hirokuni Mizoguchi, Tobias Fleischmann, Masato Komuro, Takahiro Hirai, Akiko Ikeda, Kojiro Saito, Tomohiro Watahiki, Gentaro Tajima","doi":"10.1080/14712598.2024.2371042","DOIUrl":"10.1080/14712598.2024.2371042","url":null,"abstract":"<p><strong>Introduction: </strong>Recombinant viral-based gene therapy products, such as those incorporating adeno-associated viruses (AAVs), fall under the category of genetically modified organisms (GMOs). The European Union (EU) countries and Japan must obtain environmental risk assessment (ERA) approval for the use of GMOs before starting any clinical trials. It has been reported that the development of GMO-containing products in these two regions encounters several regulatory obstacles due to the longer regulatory procedures and document preparation for ERA.</p><p><strong>Areas covered: </strong>In this article, we comparatively analyzed the ERA document requirements in the EU and Japan for AAV-based recombinant medicinal products to highlight the differences in the context of potential future attempts of convergence. Additionally, we analyzed non-clinical and clinical shedding data requirements, which are key components of ERA reviews in the EU and Japan. Lastly, we compared the containment measures to minimize the spread of GMOs in the environment in the EU and Japan.</p><p><strong>Expert opinion: </strong>Based on our comparative analysis, we present several policy recommendations of standardizing and simplifying the application materials and procedures for the ERA regulations on GMOs in the EU and Japan in the mid-, and long-term timeframe to achieve global regulatory convergence.</p>","PeriodicalId":12084,"journal":{"name":"Expert Opinion on Biological Therapy","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141450211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}