BioDrugs最新文献

{"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}

{"title":"CRISPR-Cas System: A New Dawn to Combat Antibiotic Resistance","authors":"Muhammad Shahzad Rafiq, Muhammad AbuBakar Shabbir, Ahmed Raza, Shoaib Irshad, Andleeb Asghar, Muhammad Kashif Maan, Mushtaq Ahmed Gondal, Haihong Hao","doi":"10.1007/s40259-024-00656-3","DOIUrl":"https://doi.org/10.1007/s40259-024-00656-3","url":null,"abstract":"<p>Antimicrobial resistance (AMR) can potentially harm global public health. Horizontal gene transfer (HGT), which speeds up the emergence of AMR and increases the burden of drug resistance in mobile genetic elements (MGEs), is the primary method by which AMR genes are transferred across bacterial pathogens. New approaches are urgently needed to halt the spread of bacterial diseases and antibiotic resistance. Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR), an RNA-guided adaptive immune system, protects prokaryotes from foreign DNA like plasmids and phages. This approach may be essential in limiting horizontal gene transfer and halting the spread of antibiotic resistance. The CRISPR-Cas system has been crucial in identifying and understanding resistance mechanisms and developing novel therapeutic approaches. This review article investigates the CRISPR-Cas system’s potential as a tool to combat bacterial AMR. Antibiotic-resistant bacteria can be targeted and eliminated by the CRISPR-Cas system. It has been proven to be an efficient method for removing carbapenem-resistant plasmids and regaining antibiotic susceptibility. The CRISPR-Cas system has enormous potential as a weapon against bacterial AMR. It precisely targets and eliminates antibiotic-resistant bacteria, facilitates resistance mechanism identification, and offers new possibilities in diagnostics and therapeutics.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":"95 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140592503","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":"Next-Generation Anti-TNFα Agents: The Example of Ozoralizumab","authors":"Kouhei Tsumoto, Tsutomu Takeuchi","doi":"10.1007/s40259-024-00648-3","DOIUrl":"https://doi.org/10.1007/s40259-024-00648-3","url":null,"abstract":"<p>Biologic therapy involving anti-tumor necrosis factor-α (anti-TNFα) agents has fundamentally changed the management of patients with immune-mediated inflammatory diseases, including rheumatoid arthritis, thus benefiting many patients. Nevertheless, the inability of some patients to achieve low disease activity or clinical remission remains a major concern. To address such concerns, next-generation anti-TNFα agents that differ from the immunoglobulin G-format anti-TNFα agents that have been used to date are being developed using antibody-engineering technology. Their unique design employing novel molecular characteristics affords several advantages, such as early improvement of clinical symptoms, optimization of drug bioavailability, enhancement of tissue penetration, and a reduction in side effects. This holds promise for a new paradigm shift in biologic therapy via the use of next-generation anti-TNFα agents. Ozoralizumab, a next-generation anti-TNFα agent that was recently approved in Japan, comprises a variable region heavy-chain format. It has a completely different structure from conventional therapeutic antibodies, such as a small molecular size, an albumin-binding module, and a unique format that produces an avidity effect. Ozoralizumab exhibited rapid biodistribution into joints, provided attenuation of Fcγ receptor-mediated inflammatory responses, and had a high binding affinity to TNFα in non-clinical studies. In clinical trials, ozoralizumab yielded an early improvement in clinical symptoms, a sustained efficacy for up to 52 weeks, and an acceptable tolerability in patients with rheumatoid arthritis. This review focuses on the results of pre-clinical and clinical trials for ozoralizumab and outlines the progress in next-generation antibody development.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":"27 1","pages":""},"PeriodicalIF":6.8,"publicationDate":"2024-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140592233","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":"Could a Long-Acting Prodrug of SN-38 be Efficacious in Sacituzumab Govitecan-Resistant Tumors?","authors":"Daniel V Santi, Gary W Ashley, Luc Cabel, Francois-Clement Bidard","doi":"10.1007/s40259-024-00643-8","DOIUrl":"10.1007/s40259-024-00643-8","url":null,"abstract":"<p><p>We previously proposed that sacituzumab govitecan (SG, Trodelvy®) likely acts as a simple prodrug of systemic SN-38 as well as an antibody drug conjugate (ADC). In the present commentary, we assess whether a long-acting SN-38 prodrug, such as PLX038, might be efficacious in SG-resistant patients. We first describe possible mechanisms of action of SG, with new insights on pharmacokinetics and TROP2 receptor occupancy. We argue that SG is not an optimal conventional ADC and that the amount of systemic SN-38 spontaneously hydrolyzed from the ADC is so high it must have activity. Then, we describe the concept of time-over-target as related to the pharmacology of SG and PLX038 as SN-38 prodrugs. To be clear, we are not in any way suggesting that PLX038 or any SN-38 prodrug is superior to SG as an anticancer agent. Clearly, SG has the benefit over antigen-independent SN-38 prodrugs in that it targets cells with the TROP2 receptor. However, we surmise that PLX038 should be a more efficacious and less toxic prodrug of systemic SN-38 than SG. Finally, we suggest possible mechanisms of SG resistance and how PLX038 might perform in the context of each. Taken together, we argue that-contrary to many opinions-SG does not exclusively act as a conventional ADC, and propose that PLX038 may be efficacious in some settings of SG-resistance.</p>","PeriodicalId":9022,"journal":{"name":"BioDrugs","volume":" ","pages":"171-176"},"PeriodicalIF":6.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10912420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139485112","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}