Drugs最新文献

{"title":"Safety and Longevity of Intraocular Pressure Control After Bimatoprost Implant Administration: Interim Analysis of a Phase 3b Clinical Trial (TRITON).","authors":"Steven M Silverstein, Francesco Oddone, Miriam Kolko, Christian K Brinkmann, William C Christie, Amanda K Bicket, Petrus N J Gous, Jan Luebke, Jyotsna Maram, Ashley Nguyen, E Randy Craven, Yongjia Pu, Jenny Jiao, Marina Bejanian, Michael R Robinson","doi":"10.1007/s40265-025-02154-4","DOIUrl":"10.1007/s40265-025-02154-4","url":null,"abstract":"<p><strong>Background: </strong>Bimatoprost implant 10 µg is an intracameral, biodegradable implant that slowly releases bimatoprost to lower intraocular pressure (IOP). This study was designed to evaluate safety and the duration of the IOP-lowering effect after single and as-needed repeat administration of the bimatoprost implant in patients with open-angle glaucoma (OAG) and ocular hypertension (OHT).</p><p><strong>Patients and methods: </strong>This study is an interim analysis of an ongoing, prospective, open-label, multicenter study in patients with OAG or OHT who are inadequately managed with topical IOP-lowering medication for reasons other than efficacy. IOP-lowering rescue treatment is allowed if implant retreatment criteria are not met. The primary endpoint is time to retreatment/rescue after the initial implant administration analyzed with the Kaplan-Meier method. Key safety measures include treatment-emergent adverse events (TEAEs) and reading-center evaluation of central corneal endothelial cell density (CECD). Analysis of data collected through 15 September 2023 focused on outcomes after a single or two implants.</p><p><strong>Results: </strong>In total, 441 patients received the 10-µg bimatoprost implant in the study eye on day 1 (cycle 1), 179 patients received a second administration (cycle 2), and 378 patients had at least 12 months of follow-up data available. The median time (95% confidence interval) from the first administration to a second administration or rescue was 392 (369, 485) days; the probability of not requiring retreatment or rescue by day 360 was 57.5%. A second implant administration similarly provided a long duration of IOP control. The baseline mean (standard error, SE) IOP was 25.6 (0.14) mmHg; the mean (SE) change from baseline IOP in unrescued eyes after a single administration was - 7.5 (0.21) mmHg at week 24 and - 6.4 (0.28) mmHg at month 12. Conjunctival hyperemia, typically associated with the administration procedure, was the most common ocular TEAE (cycle 1, 14.3%; cycle 2, 12.8%). Mean (SE) percentage change in CECD from baseline at 12 months after administration was - 4.3 (0.81)% in cycle 1 and - 8.5 (2.22)% in cycle 2. The cycle 1 implant was no longer visible or ≤ 25% of initial size in 66.3% and 94.3% of study eyes at months 12 and 24, respectively.</p><p><strong>Conclusions: </strong>In this interim analysis based on available data, the IOP-lowering effect of the initial administration of the 10-µg bimatoprost implant was well maintained for > 1 year in most patients. Results after a second administration were comparable. The safety profile of initial and repeat administration was acceptable.</p><p><strong>Trial registry: </strong>ClinicalTrials.gov identifier NCT03850782; registered 20 February 2019.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"557-570"},"PeriodicalIF":13.0,"publicationDate":"2025-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11947067/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143476367","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":"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":"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":"293-323"},"PeriodicalIF":13.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11891108/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Rezafungin: A Review in Invasive Candidiasis.","authors":"Simon Fung, Matt Shirley","doi":"10.1007/s40265-024-02134-0","DOIUrl":"10.1007/s40265-024-02134-0","url":null,"abstract":"<p><p>Rezafungin (Rezzayo^®) is a next-generation echinocandin antifungal with improved pharmacokinetic properties over first-generation echinocandins that allows for once-weekly rather than once-daily intravenous administration. It has recently been approved for the treatment of adults with invasive candidiasis in the EU and UK, and is approved for adults who have limited or no alternative options for the treatment of candidaemia and invasive candidiasis in the USA. In the pivotal phase 3 ReSTORE trial, rezafungin was non-inferior to caspofungin (a first-line echinocandin antifungal agent) based both on global cure rates at day 14 and all-cause mortality rates at day 30 in adults with candidaemia or invasive candidiasis. Additionally, the once-weekly administration of rezafungin has the potential advantage of front-loading the dose and increasing drug exposure, with some evidence suggesting that rezafungin may achieve earlier infection clearance relative to caspofungin. Rezafungin was generally well tolerated, with the most common treatment-emergent adverse events being hypokalaemia, pyrexia, diarrhoea and anaemia. Therefore, rezafungin is a useful addition to the treatments currently available for invasive candidiasis in adults, with potential benefits associated with less frequent administration compared with first-generation echinocandins.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"415-423"},"PeriodicalIF":13.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255087","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":"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":"283-291"},"PeriodicalIF":13.0,"publicationDate":"2025-03-01","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":"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":"10.1007/s40265-024-02142-0","url":null,"abstract":"","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"445-446"},"PeriodicalIF":13.0,"publicationDate":"2025-03-01","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":"Ebronucimab: First Approval.","authors":"Hannah A Blair","doi":"10.1007/s40265-025-02146-4","DOIUrl":"10.1007/s40265-025-02146-4","url":null,"abstract":"<p><p>Ebronucimab (^®) is a subcutaneous fully human anti-proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody being developed by Akeso Biopharma for the treatment of dyslipidaemia. In September 2024, ebronucimab was approved in China, in combination with statins or statins and other lipid-lowering therapies, for adult patients with primary hypercholesterolaemia [including heterozygous familial hypercholesterolaemia (HeFH)] and mixed hyperlipidaemia who are unable to achieve the low-density lipoprotein cholesterol target after receiving moderate or higher doses of statins. This article summarizes the milestones in the development of ebronucimab leading to this first approval for primary hypercholesterolaemia, mixed hyperlipidaemia and HeFH.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"437-441"},"PeriodicalIF":13.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143255051","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":"Treatment of Osteoporosis and Osteoarthritis in the Oldest Old.","authors":"Nicholas Fuggle, Andrea Laslop, René Rizzoli, Nasser Al-Daghri, Majed Alokail, Ewa Balkowiec-Iskra, Charlotte Beaudart, Olivier Bruyère, Angie Botto-van Bemden, Nansa Burlet, Etienne Cavalier, Francesca Cerreta, Manju Chandran, Antonio Cherubini, Mario Miguel Coelho da Silva Rosa, Philip Conaghan, Bernard Cortet, Alfonso Cruz Jentoft, Elizabeth M Curtis, Patrizia D'Amelio, Bess Dawson-Hughes, Elaine M Dennison, Mickaël Hiligsmann, Jean-Marc Kaufman, Stefania Maggi, Radmila Matijevic, Eugene McCloskey, Daniel Messina, Daniel Pinto, Maria Concepcion Prieto Yerro, Régis Pierre Radermecker, Yves Rolland, Carla Torre, Nicola Veronese, John A Kanis, Cyrus Cooper, Jean-Yves Reginster, Nicholas C Harvey","doi":"10.1007/s40265-024-02138-w","DOIUrl":"10.1007/s40265-024-02138-w","url":null,"abstract":"<p><p>Osteoporosis and osteoarthritis are key diseases of musculoskeletal ageing and are increasing in prevalence and burden with the progressively ageing population worldwide. These conditions are thus particularly common in 'the oldest old', and there are complexities of managing them within the context of extensive multimorbidity, physical and mental disability, and polypharmacy, the rates for all of which are high in this population. In this narrative review, we explore the epidemiology of osteoporosis and osteoarthritis in the oldest old before examining trials and real-world data relating to the pharmacological treatment of these diseases in older adults, including anti-resorptives and bone-forming agents in osteoporosis and symptomatic slow-acting drugs for osteoarthritis, paracetamol, and non-steroidal anti-inflammatory drugs in osteoarthritis, recognising that the oldest old are usually excluded from clinical trials. We then review the potential benefits of nutritional interventions and exercise therapy before highlighting the health economic benefits of interventions for osteoporosis and osteoarthritis. The high prevalence of risk factors for both disease and adverse events associated with treatment in the oldest old mean that careful attention must be paid to the potential benefits of intervention (including fracture risk reduction and improvements in osteoarthritis pain and function) versus the potential harms and adverse effects. Further direct evidence relating to such interventions is urgently needed from future research.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"343-360"},"PeriodicalIF":13.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11891106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143448141","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":"Risperidone In Situ Microparticles: A Review in Schizophrenia.","authors":"Yahiya Y Syed","doi":"10.1007/s40265-024-02140-2","DOIUrl":"10.1007/s40265-024-02140-2","url":null,"abstract":"<p><p>Risperidone in situ microparticles (risperidone ISM^®) is a novel long-acting prolonged-release formulation approved in the EU and USA for treating schizophrenia in adults. Once-monthly intramuscular injections of risperidone ISM^® provide immediate and sustained therapeutic levels of risperidone, eliminating the need for loading doses or oral supplementation. In the pivotal PRISMA-3 trial in patients with acute schizophrenia exacerbation, risperidone ISM^® significantly improved Positive and Negative Syndrome Scale (primary endpoint) and Clinical Global Impression-Severity of Illness (key secondary endpoint) total scores over the 12-week double-blind phase, with improvements observed as early as day 8. Continued treatment sustained efficacy over the 12-month open-label extension phase. Risperidone ISM^® also improved social functioning and had a positive impact on health-related quality of life. Patients stable on daily oral risperidone maintained their treatment benefits after switching to monthly risperidone ISM^®. Risperidone ISM^® was generally well tolerated in clinical trials, with a safety profile consistent with that of oral risperidone. Its fast onset of action, without the need for oral supplementation or loading doses, makes risperidone ISM^® a promising long-acting injectable that could enhance treatment adherence.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"425-435"},"PeriodicalIF":13.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143390511","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":"Prospective 18-Month Study of Bimatoprost Intracameral Implant in Patients with Open-Angle Glaucoma or Ocular Hypertension in US Clinical Practice.","authors":"Eric Mann, Jeffrey A Kammer, Gagan Sawhney, Jella An, Erica C Werts, Vanessa Vera, Marcos Rivas, Hongxin Lai, Sadhana Sonparote, E Randy Craven","doi":"10.1007/s40265-025-02157-1","DOIUrl":"10.1007/s40265-025-02157-1","url":null,"abstract":"<p><strong>Background and objective: </strong>Bimatoprost implant 10 µg (Durysta) is an intracameral biodegradable implant that releases bimatoprost to lower intraocular pressure (IOP). The purpose of this study was to prospectively collect effectiveness and safety data after administration of the implant in patients with open-angle glaucoma or ocular hypertension.</p><p><strong>Methods: </strong>This phase IV, multicenter, prospective, observational, open-label, 18-month study (ARGOS) enrolled adult patients with open-angle glaucoma or ocular hypertension who were scheduled to receive the bimatoprost implant in one or both eyes. Data collected included IOP, use of topical IOP-lowering medications, treatment-emergent adverse events, and central corneal endothelial cell density. The primary endpoint was the proportion of primary (first-treated) eyes that received no additional (new) IOP-lowering treatment per standard medical care through month 6 after the implant administration.</p><p><strong>Results: </strong>A total of 217 patients (341 eyes) were enrolled, and 132 patients (60.8%) and 203 eyes (59.5%) completed the study. Most patients were on topical IOP-lowering medication before receiving the implant. After implant administration, the proportion of primary eyes that had received no additional treatment was 88.6% (95% confidence interval 86.6-90.6) at month 6 (primary endpoint) and remained high throughout the follow-up: 83.7% (95% confidence interval 80.2-87.3) at month 12 and 77.7% (95% confidence interval 73.4-82.1) at month 18. Intraocular pressure was reduced after implant administration, with mean changes in IOP from baseline at follow-up visits ranging from - 1.0 to - 2.0 mm Hg. The mean number of topical IOP-lowering medications used was also reduced, from 1.8 at baseline to 0.9 at month 12 and 1.0 at month 18. Increased IOP and dry eye were the most common ocular treatment-emergent adverse events. The mean percentage change in central corneal endothelial cell density from baseline at month 18 (central reading center evaluation) was - 3.47%. In qualitative interviews, most patients (84%, 21/25) reported overall satisfaction with their treatment outcomes.</p><p><strong>Conclusions: </strong>The bimatoprost implant helped control IOP and decrease topical medication use. Throughout the 18 months after implant administration, an estimated 77.7% of eyes required no new added medication for IOP management. Patient-reported outcomes were favorable, and the safety profile of the implant was acceptable.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov identifier NCT04647214, registered 23 November, 2020.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"397-414"},"PeriodicalIF":13.0,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11891102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143406398","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":"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":"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":"361-383"},"PeriodicalIF":13.0,"publicationDate":"2025-03-01","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}