BioDrugs最新文献

{"title":"Postmarketing Reports of Incomplete Dosing-Related Complications with Self-Injected PCSK9 Inhibitors: A Descriptive Study and Disproportionality Analysis.","authors":"Richard H Woods","doi":"10.1007/s40259-024-00664-3","DOIUrl":"10.1007/s40259-024-00664-3","url":null,"abstract":"<p><strong>Background: </strong>Evolocumab and alirocumab are self-injected proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitors indicated for low-density lipoprotein cholesterol reduction. Complications in the use or functionality of self-injection devices may precipitate incomplete dosing.</p><p><strong>Objective: </strong>This study sought to characterize postmarketing dosing failure reports involving self-injected PCSK9 inhibitors.</p><p><strong>Methods: </strong>US Food and Drug Administration Adverse Event Reporting System (FAERS) [2016-second quarter of 2023] data were utilized for a disproportionality analysis. Eight self-injected comparator medications served as referents. Medical Dictionary for Regulatory Activities preferred terms indicating explicit or probable failure to administer a complete dose classified cases. Proportional reporting ratios (PRRs) > 2.0 and lower 95% confidence intervals (CIs) > 1.0 indicated disproportionality signals. US FDA Manufacturer and User Facility Device Experience (MAUDE) [2013-2023] data underwent a narrative review.</p><p><strong>Results: </strong>During the study period, 194,781 (evolocumab, n = 152,831; alirocumab, n = 41,950) drug-event pairs and 43,725 (evolocumab, n = 38,489; alirocumab, n = 5236) cases reported to FAERS identified PCSK9 inhibitors. MAUDE contained six evolocumab reports, half describing dose omission, and no alirocumab reports. A potential dosing failure signal was detected for evolocumab (PRR 2.01; 95% CI 1.98-2.03), but not alirocumab (PRR 0.99; 95% CI 0.97-1.02), relative to pooled comparator reports. Across three case term subcategories, incomplete dosing disproportionality signals were further identified for evolocumab patient usage complication terms (PRR 3.44; 95% CI 3.38-3.50) and alirocumab device malfunction terms (PRR 2.09; 95% CI 1.98-2.22).</p><p><strong>Conclusions: </strong>Proprotein convertase subtilisin kexin type 9 inhibitor incomplete dosing-related complications are frequently reported in the postmarketing setting. Systematic efforts to understand the incidence and mechanisms of dosing failure and associated patient burdens are needed.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"589-600"},"PeriodicalIF":5.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141316623","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanisms of Action of the US Food and Drug Administration-Approved Antisense Oligonucleotide Drugs.","authors":"Angela Sang, Selena Zhuo, Adara Bochanis, José E Manautou, Raman Bahal, Xiao-Bo Zhong, Theodore P Rasmussen","doi":"10.1007/s40259-024-00665-2","DOIUrl":"10.1007/s40259-024-00665-2","url":null,"abstract":"<p><p>Antisense oligonucleotides (ASOs) are single stranded nucleic acids that target RNA. The US Food and Drug Administration has approved ASOs for several diseases. ASOs utilize three principal modes of action (MOA). The first MOA is initiated by base-pairing between the ASO and its target mRNA, followed by RNase H-dependent mRNA degradation. The second MOA is triggered by ASOs that occlude splice acceptor sites in pre-mRNAs leading to skipping of a mutation-bearing exon. The third MOA involves ASOs that sterically hinder mRNA function, often inhibiting translation. ASOs contain a variety of modifications to the sugar-phosphate backbone and bases that stabilize the ASO or render them resistant to RNase activity. RNase H-dependent ASOs include inotersen and eplontersen (for hereditary transthyretin amyloidosis), fomiversen (for opportunistic cytomegalovirus infection), mipomersen (for familial hypercholesterolemia), and tofersen [for amyotrophic lateral sclerosis (ALS)]. Splice modulating ASOs include nursinersen (for spinal muscular atrophy) and eteplirsen, golodirsen, viltolarsen, and casimersen (all for the treatment of Duchenne muscular dystrophy). In addition, a designer ASO, milasen, was used to treat a single individual afflicted with Batten disease. Since ASO design relies principally upon knowledge of mRNA sequence, the bench to bedside pipeline for ASOs is expedient compared with protein-directed drugs. [Graphical abstract available.].</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"511-526"},"PeriodicalIF":5.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11695194/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141445323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Monoclonal Antibody Generation Using Single B Cell Screening for Treating Infectious Diseases.","authors":"John S Schardt, Neelan S Sivaneri, Peter M Tessier","doi":"10.1007/s40259-024-00667-0","DOIUrl":"10.1007/s40259-024-00667-0","url":null,"abstract":"<p><p>The screening of antigen-specific B cells has been pivotal for biotherapeutic development for over four decades. Conventional antibody discovery strategies, including hybridoma technology and single B cell screening, remain widely used based on their simplicity, accessibility, and proven track record. Technological advances and the urgent demand for infectious disease applications have shifted paradigms in single B cell screening, resulting in increased throughput and decreased time and labor, ultimately enabling the rapid identification of monoclonal antibodies with desired biological and biophysical properties. Herein, we provide an overview of conventional and emergent single B cell screening approaches and highlight their potential strengths and weaknesses. We also detail the impact of innovative technologies-including miniaturization, microfluidics, multiplexing, and deep sequencing-on the recent identification of broadly neutralizing antibodies for infectious disease applications. Overall, the coronavirus disease 2019 (COVID-19) pandemic has reinvigorated efforts to improve the efficiency of monoclonal antibody discovery, resulting in the broad application of innovative antibody discovery methodologies for treating a myriad of infectious diseases and pathological conditions.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"477-486"},"PeriodicalIF":5.4,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11645890/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141490795","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Research Advances in Stem Cell Therapy for Erectile Dysfunction.","authors":"Wei Wang, Ying Liu, Zuo-Bin Zhu, Kun Pang, Jing-Kai Wang, Jun Gu, Zhen-Bei Li, Jian Wang, Zhen-Duo Shi, Cong-Hui Han","doi":"10.1007/s40259-024-00650-9","DOIUrl":"10.1007/s40259-024-00650-9","url":null,"abstract":"<p><p>Erectile dysfunction (ED) is a common clinical condition that mainly affects men aged over 40 years. Various causes contribute to the progression of ED, including pelvic nerve injury, diabetes, metabolic syndrome, age, Peyronie's disease, smoking, and psychological disorders. Current treatments for ED are limited to symptom relief and do not address the root cause. Stem cells, with their powerful ability to proliferate and differentiate, are a promising approach for the treatment of male ED and are gradually gaining widespread attention. Current uses for treating ED have been studied primarily in experimental animals, with most studies observing improvements in erectile quality as well as improvements in erectile tissue. However, research on stem cell therapy for human ED is still limited. This article summarizes the recent literature on basic stem cell research on ED, including cavernous nerve injury, aging, diabetes, and sclerosing penile disease, and describes mechanisms of action and therapeutic effects of various stem cell therapies in experimental animals. Stem cells are also believed to interact with host tissue in a paracrine manner, and improved function can be supported through both implantation and paracrine factors. To date, stem cells have shown some preliminary promising results in animal and human models of ED.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"353-367"},"PeriodicalIF":5.4,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055746/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140193292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Consensus-Based Overarching Principles and Recommendations on the Use of Biosimilars in the Treatment of Inflammatory Arthritis in the Gulf Region.","authors":"Khalid A Alnaqbi, Nasra Al Adhoubi, Sara Aldallal, Samar Al Emadi, Adeeba Al-Herz, Amin M El Shamy, Suad Hannawi, Mohammed A Omair, Sahar A Saad, Tore K Kvien","doi":"10.1007/s40259-023-00642-1","DOIUrl":"10.1007/s40259-023-00642-1","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Though biologic agents have significantly improved the treatment of inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis, and axial spondyloarthritis), high costs, stringent regulations, strict reimbursement criteria, and existing patents have limited patient access to treatments. While being highly similar in quality, safety, and efficacy to biologic reference products, biosimilars can reduce the financial burden and prevent underutilization of medication.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The objective of this initiative was to develop an evidence-based consensus of overarching principles and recommendations aimed at standardizing the use of biosimilars in treating inflammatory arthritis in the Gulf region.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A task force of practicing rheumatologists, a clinical pharmacist, a health economist, patients, regulators, and payors from across the Gulf region developed recommendations and overarching principles based on the outputs of a systematic literature review conducted to address Patient-Intervention-Comparison-Outcome (PICO) questions specific to key challenges regarding the use of biosimilars for the treatment of inflammatory arthritis in the region. As the data before 2017 have been previously reviewed in another publication, the current review focused on data published between January 2017 and August 2022 (PROSPERO ID CRD42022364002). Consensus on each statement required a level of agreement of 70% or greater.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Consensus was reached for five overarching principles and nine recommendations by the task force. The principles emphasize the importance of improving the awareness, understanding, and perception of biosimilars, as well as the need for regulated regional real-world data generation and protocols to make biosimilars a viable and affordable treatment option for all patients. The consensus recommendations advocate the need for shared treatment decisions between rheumatologists and patients when considering biosimilars. They further recommend that confirmation of a biosimilar's efficacy and safety in a single indication is sufficient for extrapolation to other diseases for which the reference product has been approved. Finally, there is a need for pharmacovigilance and national health policies governing the adoption and prescription of biosimilars in clinical practice across the region.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;These are the first consensus recommendations for the Gulf region based on a systematic literature review and Preferred Reporting Items for Systematic Review and Meta-analysis (PRISMA) guidelines, integrating clinical evidence with clinical expertise to optimize decision making for the use of biosimilars in patients with inflammatory arthritis. They were formulated based on predominantly international data because of the limited regional data and therefore can be generalized to serve as recommendations for healthcar","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"449-463"},"PeriodicalIF":6.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055752/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139943813","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeted Gene Insertion: The Cutting Edge of CRISPR Drug Development with Hemophilia as a Highlight.","authors":"Zhenjie Zhang, Siqi Zhang, Hoi Ting Wong, Dali Li, Bo Feng","doi":"10.1007/s40259-024-00654-5","DOIUrl":"10.1007/s40259-024-00654-5","url":null,"abstract":"<p><p>The remarkable advance in gene editing technology presents unparalleled opportunities for transforming medicine and finding cures for hereditary diseases. Human trials of clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein-9 nuclease (Cas9)-based therapeutics have demonstrated promising results in disrupting or deleting target sequences to treat specific diseases. However, the potential of targeted gene insertion approaches, which offer distinct advantages over disruption/deletion methods, remains largely unexplored in human trials due to intricate technical obstacles and safety concerns. This paper reviews the recent advances in preclinical studies demonstrating in vivo targeted gene insertion for therapeutic benefits, targeting somatic solid tissues through systemic delivery. With a specific emphasis on hemophilia as a prominent disease model, we highlight advancements in insertion strategies, including considerations of DNA repair pathways, targeting site selection, and donor design. Furthermore, we discuss the complex challenges and recent breakthroughs that offer valuable insights for progressing towards clinical trials.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"369-385"},"PeriodicalIF":6.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055778/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140136450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety of Biological Therapies for Severe Asthma: An Analysis of Suspected Adverse Reactions Reported in the WHO Pharmacovigilance Database.","authors":"Paola Maria Cutroneo, Elena Arzenton, Fabiana Furci, Fabio Scapini, Maria Bulzomì, Nicoletta Luxi, Marco Caminati, Gianenrico Senna, Ugo Moretti, Gianluca Trifirò","doi":"10.1007/s40259-024-00653-6","DOIUrl":"10.1007/s40259-024-00653-6","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;The management of uncontrolled severe asthma has greatly improved since the advent of novel biologic therapies. Up to August 2022, five biologics have been approved for the type 2 asthma phenotype: anti-IgE (omalizumab), anti-IL5 (mepolizumab, reslizumab, benralizumab), and anti-IL4 (dupilumab) monoclonal antibodies. These drugs are usually well tolerated, although long-term safety information is limited, and some adverse events have not yet been fully characterized. Spontaneous reporting systems represent the cornerstone for the detection of potential signals and evaluation of the real-world safety of all marketed drugs.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;The aim of this study was to provide an overview of safety data of biologics for severe asthma using VigiBase, the World Health Organization global pharmacovigilance database.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We selected all de-duplicated individual case safety reports (ICSRs) attributed to five approved biologics for severe asthma in VigiBase, up to 31st August 2022 (omalizumab, mepolizumab, reslizumab, benralizumab and dupilumab). Descriptive frequency analyses of ICSRs were carried out both as a whole class and as individual products. Reporting odds ratios (ROR) with 95% confidence intervals (CIs) were used as the measure of disproportionality for suspected adverse drug reactions (ADRs) associated with the study drugs compared with either all other suspected drugs (Reference Group 1, RG1) or inhaled corticosteroids plus long-acting β-agonists (ICSs/LABAs) (Reference Group 2, RG2) or with oral corticosteroids (OCSs) (Reference Group 3, RG3).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Overall, 31,724,381 ICSRs were identified in VigiBase and 167,282 (0.5%) were related to study drugs; the remaining reports were considered as RG1. Stratifying all biologic-related ICSRs by therapeutic indication, around 29.4% (n = 48,440) concerned asthma use; omalizumab was mainly indicated as the suspected drug (n = 20,501), followed by dupilumab, mepolizumab, benralizumab and reslizumab. Most asthma ICSRs concerned adults (57%) and women (64.1%). Asthma biologics showed a higher frequency of serious suspected ADR reporting than RG1 (41.3% vs 32.3%). The most reported suspected ADRs included asthma, dyspnea, product use issue, drug ineffective, cough, headache, fatigue and wheezing. Asthma biologics were disproportionally associated with several unknown or less documented adverse events, such as malignancies, pulmonary embolism and deep vein thrombosis with omalizumab; alopecia and lichen planus with dupilumab; alopecia and herpes infections with mepolizumab; alopecia, herpes zoster and eosinophilic granulomatosis with polyangiitis related to benralizumab; and alopecia with reslizumab.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The most frequently reported suspected ADRs of asthma biologics in VigiBase confirmed the presence of well-known adverse effects such as general disorders, injection-site re","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"425-448"},"PeriodicalIF":6.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055782/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140136449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of Biosimilars: A Systematic Review of Published Position Statements and Recommendations from Health Organisations and Societies.","authors":"Noraisyah Mohd Sani, Zoriah Aziz, Adeeba Kamarulzaman","doi":"10.1007/s40259-024-00649-2","DOIUrl":"10.1007/s40259-024-00649-2","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Hesitation about using biosimilars still exists among healthcare professionals (HCPs), despite extensive experience with their use. Globally, several health organisations and societies from various specialties have issued biosimilar position statements to guide the use of biosimilars in their specialties. However, it is uncertain how similar or different their positions or recommendations are or whether these positions have evolved with the increased experience and availability of new evidence.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objectives: &lt;/strong&gt;The study aimed to describe and assess the recommendations of published position statements regarding several aspects of biosimilars across specialties and determine whether these positions have changed with the emergence of new evidence.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We systematically searched for published position statements of biosimilars in online databases and included statements written in English. The search was from the inception of the databases until May 2023. Two reviewers independently extracted the data. Only position statements that included recommendations to guide the use of biosimilars in clinical practice and were issued by health organisations and societies, including expert panels, were included. We synthesised recommendations on five aspects: prescribing practice, extrapolation of indication, interchangeability, treatment initiation with biosimilars in biologic-naïve patients, and pharmacovigilance.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;The review included 25 papers involving eight specialties, 16 of which were from European countries, 1 from an international organisation representing 49 countries, and 6 from various countries. The papers were published between 2009 and 2020, with 19 published between 2015 and 2020. Of the five aspects of biosimilars assessed, nearly half (11 of 25) of the papers at the time they were published did not base their positions on a scientific or evidence-based approach. Only 4 of the 25 position papers were identified as revisions of their previous papers. With increasing experience in biosimilars and the emergence of new evidence, about 60% (16 of 25) of the papers contained outdated recommendations, particularly on two aspects. They were extrapolations of indications and interchangeability (including switching). The recommendations for most papers for three other aspects were still appropriate. These were prescribing biosimilars by their brand name and active ingredient, initiating treatment with biosimilars in biologic-naïve patients, and monitoring the long-term safety of biosimilars through pharmacovigilance. For four of the revised papers, their position evolved from opposing indication extrapolation for biosimilars to accepting it, while the position of two papers shifted from not recommending biosimilar switching to permitting the practice. Meanwhile, most papers were against automatic substitution by pharmacists because the evidence f","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"405-423"},"PeriodicalIF":6.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140109128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Additional Data in Expanded Patient Populations and New Indications Support the Practice of Biosimilar-to-Biosimilar Switching.","authors":"Hillel P Cohen, Wolfram Bodenmueller","doi":"10.1007/s40259-024-00655-4","DOIUrl":"10.1007/s40259-024-00655-4","url":null,"abstract":"<p><p>As of 31 December, 2023, 31 observational studies have been published, including a total of 6081 patients who underwent a switch from one biosimilar to another biosimilar of the same reference biologic. Most studies evaluated infliximab, while a smaller number evaluated adalimumab, rituximab or etanercept. Indications studied now include sarcoidosis, as well as the indications previously reported of rheumatoid arthritis, psoriatic arthritis, axial spondyloarthritis/ankylosing spondylitis and inflammatory bowel disease (Crohn's disease and ulcerative colitis). This updated data set includes eight additional studies and 2386 more patients compared with those included in an earlier systematic review of biosimilar-to-biosimilar switching. In addition, since the earlier systematic review was published in 2022, the European Medicines Agency has stated that reference-to-biosimilar and biosimilar-to-biosimilar switching in the European Union is safe and efficacy remains unchanged after switching. Furthermore, following a review of the available evidence, the US Food and Drug Administration has confirmed that initial safety and immunogenicity concerns related to biosimilar switching are unfounded and that no differences are observed in efficacy, safety or immunogenicity following one or more switches. The availability of this new efficacy and safety data together with the supportive statements from the European Medicines Agency and the Food and Drug Administration re-confirm the conclusion that as a scientific matter, biosimilar-to-biosimilar switching is an effective clinical practice, with no new safety concerns. Any suggestions to the contrary are not supported by the evidence.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"331-339"},"PeriodicalIF":6.8,"publicationDate":"2024-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140193291","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of Early Access Reform on Oncology Innovation in France: Approvals, Patients, and Costs","authors":"Tess Martin, Catherine Rioufol, Bertrand Favier, Nicolas Martelli, Isabelle Madelaine, Christos Chouaid, Isabelle Borget","doi":"10.1007/s40259-024-00658-1","DOIUrl":"https://doi.org/10.1007/s40259-024-00658-1","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>An ambitious reform of the early access (EA) process was set up in July 2021 in France, aiming to simplify procedures and accelerate access to innovative drugs.</p><h3 data-test=\"abstract-sub-heading\">Objective</h3><p>This study analyzes the characteristics of oncology drug approvals through the EA process and its impact on real-life data for oncology patients.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>The number and characteristics of EA demands concerning oncology drugs submitted to the National Health Authority (HAS, Haute Autorité de Santé) were reviewed until 31 December 2022. A longitudinal retrospective study on patients treated with an EA oncology drug between 1 January 2019 and 31 December 2022 was also performed using the French nationwide claims database (Systeme National des Données de Santé [SNDS]) to assess the impact of the reform on the number of indications and patients, and the costs.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Among 110 published decisions, the HAS granted 88 (80%) EA indications within 70 days of assessment on average, including 46 (52%) in oncology (67% in solid tumors and 33% in hematological malignancies). Approved indications were mostly supported by randomized phase III trials (67%), whereas refused EA relied more on non-randomized (57%) trials. Overall survival was the primary endpoint of 28% of EA approvals versus none of denied EAs. In the SNDS data, the annual number of patients with cancer treated with an EA drug increased from 3137 patients in 2019 to 18,341 in 2022 (+ 484%), whereas the number of indications rose from 12 to 62, mainly in oncohematology (<i>n</i> = 17), lung (<i>n</i> = 12), digestive (<i>n</i> = 9) and breast cancer (<i>n</i> = 9). Reimbursement costs for EA treatments surged from €42 to €526 million (+ 1159%).</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>The French EA reform contributed to enabling rapid access to innovations in a wide range of indications for oncology patients. However, the findings highlight ongoing challenges in financial sustainability, warranting continued evaluation and adjustments.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":"1 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140628451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}