Drugs最新文献

{"title":"Tuberculosis Preventive Treatment in High TB-Burden Settings: A State-of-the-Art Review.","authors":"Violet Chihota, Makaita Gombe, Amita Gupta, Nicole Salazar-Austin, Tess Ryckman, Christopher J Hoffmann, Sylvia LaCourse, Jyoti S Mathad, Vidya Mave, Kelly E Dooley, Richard E Chaisson, Gavin Churchyard","doi":"10.1007/s40265-024-02131-3","DOIUrl":"10.1007/s40265-024-02131-3","url":null,"abstract":"<p><p>Tuberculosis (TB) is the leading cause of death from a single infectious agent. The burden is highest in some low- and middle-income countries. One-quarter of the world's population is estimated to have been infected with TB, which is the seedbed for progressing from TB infection to the deadly and contagious disease itself. Although some individuals may clear their infections through innate and acquired immunity, many do not. People living with HIV, TB-exposed household contacts, other individuals recently infected, and immunosuppressed individuals are at especially high risk of progressing to TB disease. There have been major advances in recent years to support the programmatic management of TB infection. New tests of infection, including those that predict progression to TB disease, have become available. Numerous World Health Organization-recommended TB preventive treatment (TPT) regimens are available for all ages and for both drug-susceptible and drug-resistant TB infection. All regimens are generally safe, efficacious, and cost effective and have a low risk of generating resistance. TPT is recommended for pregnant women who are at risk for developing TB, but some regimens are associated with an increased likelihood of poor obstetric and fetal outcomes, and newer regimens have not yet been tested in pregnancy. New formulations of rifapentine-based TPT have been developed, and the cost has been radically reduced. Innovative models of delivery to support the scale up of TPT have been developed. Modeling suggests that scaling up TPT, especially regimens with optimal target product profile characteristics, can contribute substantially to ending the TB epidemic. The global uptake of TPT has increased substantially, especially for people living with HIV. Implementation gaps remain, particularly for children, pregnant women, and other household contacts. Further innovation is required to support the continued scale up of TPT and to contribute to ending the TB epidemic.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"127-147"},"PeriodicalIF":13.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11802714/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142893029","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Marstacimab: First Approval.","authors":"Yvette N Lamb","doi":"10.1007/s40265-024-02130-4","DOIUrl":"10.1007/s40265-024-02130-4","url":null,"abstract":"<p><p>Marstacimab (marstacimab-hncq; HYMPAVZI™) is a subcutaneously administered human monoclonal immunoglobulin G1 antibody against tissue factor pathway inhibitor (TFPI) that is being developed by Pfizer for the treatment of hemophilia A and B. Marstacimab received its first approval on 11 October 2024 in the USA. It was approved for use as routine prophylaxis to prevent or reduce the frequency of bleeding episodes in adult and pediatric patients 12 years of age and older with hemophilia A without factor VIII inhibitors or hemophilia B without factor IX inhibitors. Marstacimab has since been approved on 18 Nov in the EU for the treatment of adults and adolescents with severe hemophilia A or B without inhibitors. This article summarizes the milestones in the development of marstacimab leading to this first approval for hemophilia.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"263-269"},"PeriodicalIF":13.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142881778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Buprenorphine Pharmacodynamics: A Bridge to Understanding Buprenorphine Clinical Benefits.","authors":"Mellar Davis","doi":"10.1007/s40265-024-02128-y","DOIUrl":"10.1007/s40265-024-02128-y","url":null,"abstract":"<p><p>Buprenorphine is an agonist at the mu opioid receptor (MOR) and antagonist at the kappa (KOR) and delta (DOR) receptors and a nociceptin receptor (NOR) ligand. Buprenorphine has a relatively low intrinsic efficacy for G-proteins and a long brain and MOR dwell time. Buprenorphine ceiling on respiratory depression has theoretically been related multiple factors such as low intrinsic efficacy at MOR, binding to six-transmembrane MOR and interactions in MOR/NOR heterodimers. Buprenorphine reduces analgesic tolerance by acting as a delta opioid receptor (DOR) antagonist. As a kappa opioid receptor (KOR) antagonist, buprenorphine reduces craving associated with addiction. Buprenorphine is a model opioid for the ordinal bifunctional analogs BU10038, BU08028 which have been shown to be potent analgesics in non-human primates without reinforcing effects and little to no respiratory depression.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"215-230"},"PeriodicalIF":13.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Fulzerasib: First Approval.","authors":"Yvette N Lamb","doi":"10.1007/s40265-025-02148-2","DOIUrl":"10.1007/s40265-025-02148-2","url":null,"abstract":"","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"281"},"PeriodicalIF":13.0,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143002184","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Emerging Immunotherapies for Disease Modification of Type 1 Diabetes.","authors":"Timothy P Foster, Brittany S Bruggeman, Michael J Haller","doi":"10.1007/s40265-025-02150-8","DOIUrl":"https://doi.org/10.1007/s40265-025-02150-8","url":null,"abstract":"<p><p>Type 1 diabetes mellitus (T1DM) is characterized by the progressive, autoimmune-mediated destruction of β cells. As such, restoring immunoregulation early in the disease course is sought to retain endogenous insulin production. Nevertheless, in the more than 100 years since the discovery of insulin, treatment of T1DM has focused primarily on hormone replacement and glucose monitoring. That said, immunotherapies are widely used to interdict autoimmune and autoinflammatory diseases and are emerging as potential therapeutics seeking the preservation of β-cell function among those with T1DM. In the past 4 decades of diabetes research, several immunomodulatory therapies have been explored, culminating with the US Food and Drug Administration approval of teplizumab to delay stage 3 (clinical) onset of T1DM. Clinical trials seeking to prevent or reverse T1DM by repurposing immunotherapies approved for other autoimmune conditions and by exploring new therapeutics are ongoing. Collectively, these efforts have the potential to transform the future of diabetes care. We encapsulate the past 40 years of immunotherapy trials, take stock of our successes and failures, and chart paths forward in this new age of clinically available immune therapies for T1DM.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143052018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Current and Emerging Therapeutic Strategies for the Management of Neurotrophic Keratitis.","authors":"Javier Lacorzana, Yan Ning Neo, Laura Maubon, Daniel Sibley, Sajjad Ahmad","doi":"10.1007/s40265-025-02147-3","DOIUrl":"https://doi.org/10.1007/s40265-025-02147-3","url":null,"abstract":"<p><p>Neurotrophic keratitis is a rare eye condition characterised by reduced or absent corneal sensation. This leads to impaired corneal healing through a loss of protective mechanisms such as blinking. The cornea becomes vulnerable to persistent epithelial defects, ulceration, infection and ultimately, vision loss or loss of the eye. Treatment strategies aim to protect the corneal surface and promote re-epithelialisation. Established treatments include specialised eye drops such as blood serum eye drops and topical nerve growth factor. In some cases, surgical interventions or procedures such as amniotic membrane transplantation or corneal neurotisation may be necessary. Emerging therapeutic drug options include insulin drops, BRM424, CSB-001 and varenicline. The aim of this Current Opinion is to introduce and review this field for the general reader, paying particular attention to emerging drug therapies for neurotrophic keratitis.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibacterials with Novel Chemical Scaffolds in Clinical Development.","authors":"Dominik Heimann, Daniel Kohnhäuser, Alexandra Jana Kohnhäuser, Mark Brönstrup","doi":"10.1007/s40265-024-02137-x","DOIUrl":"https://doi.org/10.1007/s40265-024-02137-x","url":null,"abstract":"<p><p>The rise of antimicrobial resistance represents a significant global health threat, driven by the diminishing efficacy of existing antibiotics, a lack of novel antibacterials entering the market, and an over- or misuse of existing antibiotics, which accelerates the evolution of resistant bacterial strains. This review focuses on innovative therapies by highlighting 19 novel antibacterials in clinical development as of June 2024. These selected compounds are characterized by new chemical scaffolds, novel molecular targets, and/or unique mechanisms of action, which render their potential to break antimicrobial resistance particularly high. A detailed analysis of the scientific foundations behind each of these compounds is provided, including their pharmacodynamic profiles, current development state, and potential for overcoming existing limitations in antibiotic therapy. By presenting this subset of chemically novel antibacterials, the review highlights the ability to innovate in antibiotic drug development to counteract bacterial resistance and improve treatment outcomes.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022638","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting HER2 in Gastroesophageal Cancer: A New Appetite for an Old Plight.","authors":"Antonella Cammarota, Rachel Woodford, Elizabeth C Smyth","doi":"10.1007/s40265-024-02132-2","DOIUrl":"https://doi.org/10.1007/s40265-024-02132-2","url":null,"abstract":"<p><p>The incidence of gastroesophageal cancers is rising, driven, in part, by an increasing burden of risk factors of obesity and gastroesophageal reflux. Despite efforts to address these risk factors, and a growing interest in methods of population screening, the bulk of these tumours are unresectable at diagnosis. In this setting, effective systemic treatments are paramount to improve survival and quality of life. Early and accurate identification of oncogenic drivers, such as human epidermal growth factor receptor 2 (HER2), present in 5-30% of gastroesophageal adenocarcinomas (GEAs), is integral to guide choice of therapies due to the clear predictive implications that arise from overexpression of this receptor. After trastuzumab, the first anti-HER2 agent with approved use in HER2-positive GEA, the addition of pembrolizumab to first-line trastuzumab-chemotherapy and trastuzumab deruxtecan in the refractory space have more recently changed practice. Yet, the response to these agents has been vastly different across patients with HER2-positive disease, underpinning the need for reliable biomarkers of response. Emergent data have suggested that levels of HER2 expression on tissue or liquid biopsies may predict response to first-generation HER2 therapies while HER2 heterogeneity, receptor changes, co-occurring molecular alterations and oncogenic genomic and metabolic reprogramming may be implicated in resistance. A robust knowledge of the mechanisms of resistance and response to HER2-directed therapies is necessary to inform novel strategies of HER2-targeting and guide choice combinations with other biomarker-directed therapies, to improve outcomes from a new generation of clinical trials in HER2-positive GEA. Understanding and close examination of previous failures in this space form an important part of this assessment, as does correlative biomarker and translational work pertaining to the role of HER2 and dynamic changes that result through treatment exposure. In this review, we aim to provide an overview of strategies for HER2 targeting, summarising both the successes and disappointments in this therapeutic landscape and discuss existing challenges and future perspectives on development in this highly morbid tumour type.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143022566","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Authors' Reply to Purchase's Comment on \"Trientine Tetrahydrochloride, from Bench to Beside: A Narrative Review\".","authors":"C Omar F Kamlin, Timothy M Jenkins, Jamie L Heise, Naseem S Amin","doi":"10.1007/s40265-024-02142-0","DOIUrl":"https://doi.org/10.1007/s40265-024-02142-0","url":null,"abstract":"","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142968974","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comment on \"Trientine Tetrahydrochloride, From Bench to Bedside: A Narrative Review\".","authors":"Rupert Purchase","doi":"10.1007/s40265-024-02141-1","DOIUrl":"10.1007/s40265-024-02141-1","url":null,"abstract":"","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":""},"PeriodicalIF":13.0,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142969843","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}