Drugs最新文献

{"title":"Baxdrostat: First Approval.","authors":"Hannah A Blair","doi":"10.1007/s40265-026-02373-3","DOIUrl":"10.1007/s40265-026-02373-3","url":null,"abstract":"<p><p>Baxdrostat (BAXFENDY^™) is a first-in-class, highly selective and potent aldosterone synthase inhibitor being developed by AstraZeneca for the treatment of hypertension, chronic kidney disease (CKD) and primary aldosteronism, and for the prevention of heart failure. On 15 May 2026, baxdrostat received its first approval in the USA for the treatment of hypertension in combination with other antihypertensive drugs, to lower blood pressure (BP) in adults who are not adequately controlled on other agents. This article summarizes the milestones in the development of baxdrostat leading to this first approval for hypertension.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1761-1768"},"PeriodicalIF":14.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789590","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":"Plasma Biomarker Effects of Oral Valiltramiprosate/ALZ-801 in Early Alzheimer's Disease from Phase 3 and Phase 2 Trials: Analysis of Core Biomarkers and Correlations with Clinical and Neuroimaging Outcomes.","authors":"John A Hey, Susan Abushakra, Aidan Power, David Watson, Anton Porsteinsson, Marwan Sabbagh, Emer MacSweeney, Sharon Cohen, Mercè Boada, P Murali Doraiswamy, Fanny M Elahi, Robert A Rissman, Earvin Liang, Susan Flint, Elitza Hristova, Patrick Kesslak, Rosalind McLaine, Adem Albayrak, Jean F Schaefer, Jeremy Y Yu, Luke Tolar, Martin Tolar","doi":"10.1007/s40265-026-02381-3","DOIUrl":"10.1007/s40265-026-02381-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Alzheimer's disease (AD) is a progressive neurodegenerative disorder with few treatment options, especially for APOE4/4 homozygotes who carry high genetic risk. Valiltramiprosate/ALZ-801 is an oral small-molecule inhibitor of amyloid-beta oligomer formation in late-stage development as a disease-modifying therapy for AD. A recent Phase 3 trial did not meet its primary clinical endpoint in the overall population, but demonstrated significant benefits in cognition, function, and brain volumetric MRI (vMRI) in the prespecified subgroup with mild cognitive impairment (MCI). Here, we report plasma p-tau217, p-tau217/Aβ42, and neurofilament light chain (NfL) results from the Phase 3 trial, along with 4-year fluid biomarker data from the Phase 2 study in APOE4 carriers with early AD.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;The 78-week, APOLLOE4 Phase 3 trial randomized APOE4/4 homozygotes to placebo (n = 162) or valiltramiprosate 265 mg BID (n = 163). The Phase 2 trial was an open-label biomarker study in APOE4 carriers with early AD who received valiltramiprosate 265 mg BID (N = 84) for 104 weeks, followed by a 2-year extension on the same regimen. Plasma p-tau217 and p-tau217/Aβ42 were measured every 6 months in both trials using FDA-approved Fujirebio Lumipulse G assay. Plasma NfL was measured in the Phase 3 trial using the Simoa assay. Associations between plasma biomarkers and clinical or vMRI outcomes were assessed using Spearman's correlation. Data are reported separately by study.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Baseline plasma p-tau217/Aβ42 confirmed amyloid positivity in 94% of 294 Phase 3 APOE4/4 subjects, including 91% of those with MCI, as well as in 97% of 80 Phase 2 subjects. In the overall Phase 3 population, valiltramiprosate significantly reduced plasma p-tau217 compared with placebo at weeks 26, 52, and 78 (all p &lt; 0.025, observed values). A similar effect was seen in the Phase 3 MCI subgroup (p &lt; 0.05 at weeks 52 and 78), whereas the Mild AD subgroup showed only a numerical trend. In observed case analyses of MCI subjects, plasma p-tau217 decreased by 36% from baseline with valiltramiprosate and increased by 17% with placebo. In the same subgroup, the p-tau217/Aβ42 ratio decreased by 40% with valiltramiprosate and increased by 7% with placebo. Among Phase 3 MCI subjects, week 78 reductions in p-tau217 correlated significantly with improvements in ADAS-Cog13 (r = 0.276, p = 0.039), CDR-SB (r = 0.377, p = 0.005), hippocampal volume (r = - 0.353, p = 0.013), cortical thickness (r = - 0.337, p = 0.018), and whole brain volume (r = - 0.312, p = 0.029). Plasma NfL was also significantly lower with valiltramiprosate than placebo at week 78 in MCI subjects (p = 0.032). NfL stability over 78 weeks correlated significantly with improvements in ADAS-Cog13 (r = 0.29, p = 0.03) and hippocampal volume (r = - 0.282, p = 0.047), and with reductions in p-tau217 (r = 0.42, p = 0.001). In Phase 2 APOE4 carriers, valiltramiprosat","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1705-1721"},"PeriodicalIF":14.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615119/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148873043","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":"Alopecia Areata: Current and Emerging Therapies.","authors":"João Domingues, Brett King, Tiago Torres","doi":"10.1007/s40265-026-02371-5","DOIUrl":"10.1007/s40265-026-02371-5","url":null,"abstract":"<p><p>Alopecia areata (AA) is a chronic immune-mediated disease characterized by non-scarring hair loss and a highly heterogeneous clinical course. Historically managed with nonspecific immunosuppressive therapies, AA has undergone a major therapeutic transformation driven by advances in the understanding of its immunopathogenesis, particularly the central role of interferon-γ, interleukin-15, and other cytokines that signal through the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway as well as the development of JAK inhibitors. Targeted JAK inhibitors have emerged as the first reliably effective systemic treatments for severe AA, leading to the regulatory approval of baricitinib, ritlecitinib, and deuruxolitinib. Pivotal phase 3 trials have demonstrated clinically meaningful scalp hair regrowth with these agents, with responses often deepening over time under continuous therapy. Long-term extension studies and real-world data further support their effectiveness and manageable safety profiles in appropriately selected patients. Indirect comparative analyses suggest differences in short-term efficacy among approved JAK inhibitors, although the absence of head-to-head trials requires cautious interpretation. Beyond approved therapies, a robust pipeline bears hope that other immunomodulatory strategies can effectively address AA pathobiology. Pediatric development programs and real-world observational studies are also broadening the evidence base across age groups and clinical settings. Despite these advances, significant challenges remain. A substantial proportion of patients fail to achieve near-complete or complete regrowth, all approved medicines belong to the same drug class, and there are no agents approved for pre-adolescents. This review provides a critical overview of approved and emerging therapies for AA, integrating clinical trial data, comparative efficacy analyses, and real-world evidence, while highlighting current limitations and future directions.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1599-1618"},"PeriodicalIF":14.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789579","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":"Non-invasive Assessment and Therapeutic Targeting in Metabolic Dysfunction-Associated Steatohepatitis (MASH): Overcoming the Dissonance Between Drug Development and Precision Medicine.","authors":"Eleni Theocharidou, Konstantinos Arvanitakis, Theocharis Koufakis, Emmanouil Tsochatzis, Sven Francque, Georgios Germanidis","doi":"10.1007/s40265-026-02362-6","DOIUrl":"10.1007/s40265-026-02362-6","url":null,"abstract":"<p><p>Despite two decades of therapeutic clinical trials in metabolic dysfunction-associated steatotic liver disease (MASLD), only two drugs have been approved so far for those with metabolic dysfunction-associated steatohepatitis (MASH) with fibrosis but not cirrhosis. Treatment responses are variable and difficult to predict, reflecting the complexity of disease pathophysiology as well as the current inability to capture disease heterogeneity, all precluding making informed individualized choices that potentially might improve treatment results. Liver biopsy for diagnosis and efficacy assessment is to date a prerequisite in late-stage trials, which limits large-scale trials and translation to routine clinical practice, and also fails to capture that heterogeneity. Several non-invasive tests (NITs) have been developed as a diagnostic surrogate to reflect disease severity, mostly addressing fibrosis, which is the strongest predictor of liver-related outcomes. This article highlights the dissonance between drug development for 'at-risk' MASH that targets both active disease and fibrosis relying on strict histological criteria, and current NITs that have been proposed for patient selection for pharmacotherapy and monitoring in clinical practice but largely reflect fibrosis. Although increasing evidence suggests their usefulness in diagnosis and follow-up, their ability to capture disease heterogeneity and select the right patients for the right treatments seems limited. Emerging NITs are derived from disease pathophysiological mechanisms and integrate lipidomic and proteomic analysis with existing biomarkers, as well as with other parameters such as the genetic background, the liver microenvironment, or the gut microbiome. Utilizing novel NITs therefore has the potential to identify appropriate candidates for therapy and also monitor responses, allowing in the future for true personalized medicine. Furthermore, understanding the complex pathophysiological mechanisms can potentially unravel not only novel diagnostics but also innovative therapeutic targets. This could lead to (personalized) choices of drugs and drug combinations that engage multiple pathways to improve efficacy, not only in terms of liver disease, but also in relation to the cardiometabolic risk profile. Moving towards precision medicine in MASLD, information provided non-invasively via circulating biomarkers (liquid liver biopsy) may hence guide risk stratification and therapeutic decisions in the near future.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1619-1643"},"PeriodicalIF":14.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13614988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789538","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":"GLP-1 Receptor Agonists and Musculoskeletal Outcomes: A Systematic Literature Review and Meta-Analysis.","authors":"Charlotte Beaudart, Yveline Malréchauffé, Sophie van Heden, Dolores Sanchez-Rodriguez, André Scheen, Olivier Bruyère, Ali Mobasheri, Gustavo Duque, René Rizzoli, Jean-Yves Reginster, Jotheeswaran Amuthavalli Thiyagarajan","doi":"10.1007/s40265-026-02365-3","DOIUrl":"10.1007/s40265-026-02365-3","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Introduction: &lt;/strong&gt;Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for the treatment of type 2 diabetes and obesity, but their effects on musculoskeletal health remain completely misunderstood.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Objective: &lt;/strong&gt;This systematic review/meta-analysis aims to synthesise clinical data on the effects of GLP-1 RAs on key relevant bone, muscle, and joint outcomes.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) (both via Ovid&lt;sup&gt;®&lt;/sup&gt; platform) and Embase were searched from inception to March 2025 to identify relevant randomised controlled trials (RCTs) or real-world evidence (RWE) studies to be included. This bibliographic search was completed manually. A random-effect model meta-analysis was performed for any outcome reported in at least 2 studies. Subgroup analyses were performed on the type of GLP-1 RAs, type of comparator used and study design. Sensitivity analyses (i.e., leave-out sensitivity analyses and analyses restricted to the most adjusted effect estimate) were performed to test the robustness of the data. The strength of evidence was assessed using GRADE. This work has been performed in adherence with PRISMA statement. (PROSPERO Record ID: CRD420251024082).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;From 1148 potentially relevant references, 60 articles (46 RCTs, 13 RWE studies and 1 pharmacovigilance study, comprising 1,250,717 individuals) met our inclusion criteria. Different GLP-1 RAs were represented across the panel of studies, i.e., semaglutide, liraglutide, exenatide, dulaglutide, tirzepatide (dual agonist gastric inhibitory polypeptide [GIP]/GLP-1) and others. No effect on bone outcomes (i.e., bone mineral density [all sites] and fractures [all sites]) were observed when the meta-analytical models included the most adjusted effect size. Regarding muscle outcomes, a significant decrease of lean body mass/fat-free mass was consistently observed with GLP-1 RAs in the global model (k = 28, standardised mean difference [SMD] 0.52, 95% confidence interval [CI] -0.8; -0.23, I&lt;sup&gt;2&lt;/sup&gt; 88%, p-value for heterogeneity &lt;0.0001), which remained robust in all sensitivity analyses. Subgroup analyses showed that the effect was mainly driven by liraglutide and semaglutide, with a decrease in lean body mass/fat-free mass observed when GLP-1 RAs were compared with placebo. No publication bias was found. Regarding joint outcome, models revealed no significant change in The Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, physical function and stiffness.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;This meta-analysis is the first to investigate the effects of GLP-1 RAs on a large panel of musculoskeletal health outcomes. While no significant effects were observed on bone- or joint-related outcomes, GLP-1 RAs were associated with reductions in lean body mass/fat-free mass, although the certainty of evidence was low and these change","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1661-1691"},"PeriodicalIF":14.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615104/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955052","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":"Safety Profile of the Non-steroidal Anti-inflammatory Drug Celecoxib in the Short-Term Management of Acute Non-cancer Pain: A Systematic Review with Meta-analysis of Randomised Controlled Trials.","authors":"Carlos Mesa-Castrillon, Ye Tian, Jessica Hughes, Paula Beckenkamp, Michelle Hall, Dimitri Papadimitriou, Paulo Ferreira","doi":"10.1007/s40265-026-02377-z","DOIUrl":"10.1007/s40265-026-02377-z","url":null,"abstract":"<p><strong>Objective: </strong>To summarise the literature regarding the safety of short-term use of the non-steroidal anti-inflammatory drug (NSAID) celecoxib.</p><p><strong>Study design: </strong>Systematic review with meta-analysis of randomised trials. Participants comprised individuals of all ages with acute non-cancer pain. Interventions included celecoxib at 200-400 mg/day for up to 10 days. The comparators were placebo, other NSAIDs (including cyclooxygenase-2 [COX-2] inhibitors and non-selective NSAIDS [nsNSAIDS]), or opioids.</p><p><strong>Data sources: </strong>Five databases were searched from inception to April 2025: Embase, Web of Science, MEDLINE, Cochrane Central Register of Controlled Trials, and Scopus. Additionally, a registry was searched: ClinicalTrials.gov.</p><p><strong>Data synthesis: </strong>Meta-analyses using Mantel-Haenszel and random-effects model were used to calculate risk ratios (RRs) and 95% confidence intervals (CIs) for severe cardiovascular, respiratory, and gastrointestinal adverse events and secondary outcomes. The Cochrane Risk of Bias Tool for randomised trials (RoB-2) was used to assess bias risk. The Grading of Recommendation Assessment, Development and Evaluation (GRADE) was conducted to assess the certainty of evidence of each reported outcome.</p><p><strong>Results: </strong>Title/abstract and full text screening comprised 3976 and 273 studies, respectively. Fifty studies were included with 10,693 participants. The RRs for adverse events were no different between celecoxib and placebo for severe events (3 studies) (RR 0.44 [95% CI 0.10-2.03]), cardiovascular (3 studies) (RR 0.84 [95% CI 0.24-2.92]), respiratory (4 studies) (RR 1.23 [95% CI 0.29-5.26]), and gastrointestinal events (33 studies) (RR 0.96 [95% CI 0.64-1.43]). There was no difference between celecoxib and NSAIDS for gastrointestinal adverse events, RR 0.89 (95% CI 0.68-1.17). Celecoxib had a lower risk compared to opioids for gastrointestinal events, RR 0.34 (95% CI 0.14-0.86), and showed a lower risk of nausea compared with placebo, RR 0.75 (95% CI 0.60-0.93), and nsNSAIDS, RR 0.80 (95% CI 0.64-0.99). Most studies had some risk of bias concerns, and the overall certainty of evidence for most outcomes was very low. Celecoxib appears to be safe for acute non-cancer pain when compared to placebo, NSAIDS, and opioids. It had a lower risk compared to opioids for gastrointestinal adverse events in general, nausea and vomiting, as well as a lower risk for nausea adverse events when compared to placebo and nsNSAIDS.</p><p><strong>Registration: </strong>PROSPERO-CRD42025642152.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1693-1703"},"PeriodicalIF":14.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615030/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955068","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":"Cefepime/Zidebactam: First Approval.","authors":"Matt Shirley","doi":"10.1007/s40265-026-02374-2","DOIUrl":"10.1007/s40265-026-02374-2","url":null,"abstract":"<p><p>Cefepime/zidebactam (Zaynich^®), a fixed-dose combination of the fourth-generation cephalosporin cefepime and the β-lactam enhancer zidebactam, that is being developed by Wockhardt for the treatment of serious infections caused by multidrug-resistant Gram-negative bacteria. With synergistic properties between the two drug components, cefepime/zidebactam has demonstrated in vitro bactericidal activity even in organisms with complex resistance mechanisms. Supported by the findings of the pivotal, active-controlled, phase III ENHANCE 1 trial, on 27 May 2026, cefepime/zidebactam received its first approval, in India, for the treatment of adult patients with complicated urinary tract infections (cUTI), including pyelonephritis, as well as cases with concurrent Gram-negative bacteraemia. Subsequently, on 29 May 2026, cefepime/zidebactam was approved in the USA for the treatment of adult patients with cUTI including pyelonephritis caused by designated susceptible microorganisms. Cefepime/zidebactam is also currently under regulatory review in the EU for use in the treatment of serious infections caused by Gram-negative bacteria. This article summarises the milestones in the development of cefepime/zidebactam leading to this first approval for the treatment of cUTI (including pyelonephritis) in adults.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1753-1760"},"PeriodicalIF":14.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148789614","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":"Orforglipron: First Approval.","authors":"Matt Shirley","doi":"10.1007/s40265-026-02363-5","DOIUrl":"10.1007/s40265-026-02363-5","url":null,"abstract":"<p><p>Orforglipron (Foundayo™) is an orally administered, non-peptide glucagon-like peptide-1 (GLP-1) receptor agonist being developed by Eli Lilly and Co. for use in long-term weight management and for the treatment of type 2 diabetes (T2D) among other indications. In April 2026, orforglipron received its first approval, in the USA, for use in combination with a reduced-calorie diet and increased physical activity for long-term weight management in adults with obesity or adults with overweight in the presence of one or more weight-related comorbid condition. Orforglipron has also been submitted for regulatory review in the EU for long-term weight management and T2D, in Japan for long-term weight management, and in Canada for T2D. In addition to long-term weight management and T2D treatment, orforglipron is currently under phase III clinical evaluation for use in the treatment of obstructive sleep apnoea, hypertension, stress urinary incontinence in females, osteoarthritis pain and peripheral arterial disease. This article summarises the milestones in the development of orforglipron leading to this first approval for long-term weight management in adults with obesity or overweight.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1735-1745"},"PeriodicalIF":14.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148535550","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":"Lunsotogene Parvec: First Approval.","authors":"Aisling McGuigan","doi":"10.1007/s40265-026-02361-7","DOIUrl":"10.1007/s40265-026-02361-7","url":null,"abstract":"<p><p>Lunsotogene parvec (lunsotogene parvec-cwha; OTARMENI^™) is a dual adeno-associated virus (AAV) gene transfer therapy developed by Regeneron Pharmaceuticals for the treatment of profound, congenital hearing loss caused by OTOF variants. Delivery of the OTOF transgene to the inner hair cells facilitates production of functional otoferlin protein to restore synaptic transmission to the auditory nerve. Lunsotogene parvec received its first approval on 23 April 2026 in the USA for the treatment of paediatric and adult patients with severe-to-profound and profound sensorineural hearing loss (any frequency > 90 dB HL) associated with molecularly confirmed biallelic variants in the OTOF gene, preserved outer hair cell function and no prior cochlear implant in the same ear. This article summarises the milestones in the development of lunsotogene parvec leading to this first approval for OTOF-associated sensorineural hearing loss.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1747-1751"},"PeriodicalIF":14.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148668520","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":"Antibiotic-Refractory Chronic Pouchitis After Ileal Pouch-Anal Anastomosis: Current and Emerging Therapeutic Strategies.","authors":"Ilaria Faggiani, Connor Tuttle, Silvio Danese, Laurent Peyrin-Biroulet, Vipul Jairath, Rocio Sedano, Iris Dotan, Remo Panaccione, Christopher Ma","doi":"10.1007/s40265-026-02383-1","DOIUrl":"10.1007/s40265-026-02383-1","url":null,"abstract":"<p><p>Chronic inflammatory pouch disorders may affect up to 20% of patients within 5 years after ileal pouch-anal anastomosis and remains a major therapeutic challenge. Within this spectrum, chronic antibiotic-refractory pouchitis is associated with impaired quality of life, long-term pouch-related complications, and potential risk for pouch failure and excision. Current recommendations support the use of probiotics for primary and secondary prevention in selected patients. Increasingly, targeted advanced therapies, including biologics and small molecules approved for the treatment of ulcerative colitis and Crohn's disease, are being used to reduce antibiotic dependence and maintain disease control in patients with pouch inflammation. Vedolizumab is the only advanced therapy approved in Europe for chronic pouchitis, whereas evidence for tumor necrosis factor (TNF) antagonists, ustekinumab, and newer agents, such as interleukin (IL)-23p19 antagonists and Janus kinase (JAK) inhibitors is largely based on observational data from clinical practice and real-world experience. Fecal microbiota transplantation is biologically attractive but remains investigational, with early studies showing inconsistent efficacy. Dietary patterns may modify pouch inflammation; however, most evidence is observational. Overall, current management strategies for chronic pouchitis are limited by incomplete understanding of disease pathogenesis, and by persistent methodological gaps, including poorly standardized treatment outcomes and the lack of validated treat-to-target strategies for this population. Well designed prospective and controlled studies are needed to define appropriate antibiotic-sparing strategies, optimal treatment positioning, and long-term durability of response.</p>","PeriodicalId":11482,"journal":{"name":"Drugs","volume":" ","pages":"1577-1597"},"PeriodicalIF":14.7,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148975652","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}