The Journal of Clinical Pharmacology最新文献

{"title":"PBPK Models for Fetal Drug Exposure: A Critical Assessment of Current Approaches and Regulatory Readiness","authors":"André Dallmann PhD,&nbsp;Andrew Butler PhD,&nbsp;Sophie Fischer-Holzhausen PhD,&nbsp;Essam Kerwash PhD,&nbsp;Julia Macente PhD,&nbsp;Nina Nauwelaerts PhD,&nbsp;Sílvia M. Illamola PharmD, PhD,&nbsp;Karen Rowland Yeo PhD,&nbsp;Jane Knöchel PhD","doi":"10.1002/jcph.70271","DOIUrl":"https://doi.org/10.1002/jcph.70271","url":null,"abstract":"<p>Physiologically based pharmacokinetic (PBPK) modeling has emerged as a critical tool for predicting fetal drug exposure during pregnancy, accounting for the complex interplay of maternal physiological changes and placental transfer mechanisms. This review summarizes the current state of PBPK modeling in maternal-fetal pharmacology, discussing various modeling approaches, including compartmental structures and mathematical formulations for placental transfer, as well as approaches to parameterize placental drug transfer in humans. Furthermore, a regulatory perspective on the use of maternal-fetal PBPK models in submissions to the MHRA is provided. Despite advancements, significant gaps remain in understanding the variability of placental drug transfer across gestational stages and the implications of transporter activity. Future research should focus on generating robust clinical data and integrating innovative technologies, such as organ-on-a-chip systems, to enhance model accuracy. Additionally, regulatory acceptance of PBPK models will depend on the establishment of comprehensive validation frameworks. By fostering collaboration between researchers, clinicians, and regulatory bodies, PBPK modeling can advance toward safer therapeutic options for pregnant women and their developing fetuses, ultimately improving maternal-fetal health outcomes.</p>","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"66 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784919","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Model-Informed Decision Making from Drug Discovery to Reimbursement: A Roadmap for Clinical Pharmacology in Value-Based Healthcare","authors":"Rajesh Krishna PhD,&nbsp;Ananth Kadambi PhD,&nbsp;Patrick Smith PhD,&nbsp;Piet H. van der Graaf PharmD, PhD,&nbsp;Fran Brown PhD","doi":"10.1002/jcph.70270","DOIUrl":"https://doi.org/10.1002/jcph.70270","url":null,"abstract":"<p>The transition to value-based healthcare demands more efficient, evidence-driven approaches to drug discovery, development and medical use. Clinical pharmacology is uniquely positioned to support this shift through model-informed drug development (MIDD) decision-making, integrating quantitative methods across the product lifecycle. This commentary outlines a roadmap for embedding MIDD from early drug discovery through regulatory evaluation and ultimately into reimbursement and real-world use. We highlight how pharmacokinetic/pharmacodynamic modeling, mechanistic modeling, disease progression models, patient-relevant endpoints, and real-world data will inform dose selection, optimize trial design, and reduce uncertainty in benefit–risk and cost-effectiveness assessments. Emphasis is placed on cross-stakeholder alignment, including regulators, payers, clinicians, and industry, to ensure that model-informed evidence translates into demonstrable patient and economic value. Key challenges, such as data integration, model transparency, and acceptance by decision-makers, are discussed alongside practical solutions. By advancing a lifecycle-based, quantitatively informed framework, clinical pharmacology can play a central role in delivering therapies that are not only safe and effective but also aligned with the principles of value-based healthcare.</p>","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"66 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcph.70270","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Semaglutide-Induced Nonarteritic Anterior Ischemic Optic Neuropathy: A Systematic Review and Meta-Analysis","authors":"Elnaz Khani PharmD,,&nbsp;Hila Asham PharmD,,&nbsp;Aysa Rezabakhsh PhD,&nbsp;Shima Babaei PharmD,&nbsp;Taher Entezari-Maleki PharmD, PhD","doi":"10.1002/jcph.70248","DOIUrl":"https://doi.org/10.1002/jcph.70248","url":null,"abstract":"<p>Despite the recent reports of the potential association between semaglutide and nonarteritic anterior ischemic optic neuropathy (NAION), available evidence remains inconclusive. We aimed to evaluate the relative effect (RE) of NAION in individuals treated with semaglutide compared to the control group. The results of this systematic review and meta-analysis were reported according to the PRISMA guidelines. The study protocol was prospectively registered in PROSPERO with ID: CRD42025649542. A systematic search was performed on the PubMed, Embase, and Cochrane Library databases until May 18, 2026. Meta-analysis of REs with 95% confidence intervals (CI) was calculated using random-effects models. Eight observational cohort studies, involving a total of 5,916,559 participants, were included in the meta-analysis. Of these, 1,870,346 patients received semaglutide treatment, while 4,046,213 were administered non-semaglutide treatment. Compared to non-semaglutide-treated patients, semaglutide users had a higher risk of NAION (RE, 1.93; 95% CI, 1.22–3.08; I², 91%; <i>P</i>  =  .01). There was a significant association between NAION risk and semaglutide use in individuals with diabetes (RE, 1.84; 95% CI, 1.21–2.80; I², 88.26%; <i>P</i>  &lt; .01). However, the results were non-significant among overweight or obese individuals (RE, 1.68; 95% CI, 0.72–3.91; I², 83.98%; <i>P</i>  =  .23). The current meta-analysis suggests a possible association between semaglutide and risk of NAION. Further randomized clinical trials are required to draw a clear conclusion.</p>","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"66 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784133","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical Pharmacology in China: Seven Decades of Progress in Discipline Development and Education","authors":"Guo-Xiang Hao PhD,&nbsp;Yue Zhou PhD,&nbsp;Bo-Hao Tang PhD,&nbsp;Hua-Jun Zhao PhD,&nbsp;Wei Wei PhD,&nbsp;John van den Anker MD, PhD,&nbsp;Wei Zhao PharmD, PhD","doi":"10.1002/jcph.70262","DOIUrl":"https://doi.org/10.1002/jcph.70262","url":null,"abstract":"<p>Clinical pharmacology serves as the central discipline supporting rational clinical medication, innovative drug research, and full-lifecycle pharmaceutical supervision. Domestic clinical pharmacology research began in the 1950s, and the field entered a period of rapid development after 1979 across three phases. This study sorts domestic disciplinary milestones and analyzes three key datasets: among the 1949 registered drug clinical trial institutions nationwide, nearly 50% are located in East China; investigational new drug applications surged from 446 (2012) to 3516 (2025); and the Center for Drug Evaluation issued 631 technical guidelines. The National Natural Science Foundation set up an independent clinical pharmacology discipline classification in 2015. The multi-tiered educational system is further elaborated: the transitional 5-year pharmacy (clinical pharmacology direction) track, standardized 5-year clinical pharmacy undergraduate programs, and clinical pharmacology-oriented postgraduate research sub-disciplines under pharmacy-related majors. Although the field has built a complete framework covering basic research, clinical practice and regulatory evaluation, critical bottlenecks persist. Clinical pharmacology is not listed as an independent major in national undergraduate and postgraduate catalogues, resulting in uneven educational standards, insufficient industry–academia integration, and striking regional gaps in disciplinary resources between eastern and inland areas. China's transitional undergraduate training model and phased regulatory improvements provide practical references for pharmaceutical regulators and educators worldwide. Targeted optimization strategies are proposed to construct unified tiered educational systems, deepen cross-stakeholder collaborative innovation, and balance regional disciplinary layouts. The sound and balanced development of clinical pharmacology will continuously advance standardized clinical medication, accelerate domestic new drug innovations, and strengthen national public health protection.</p>","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"66 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, Pharmacokinetics, Food effect, and Pharmacodynamics of AJM347, a Selective α4β7 Integrin Antagonist: A First-in-Human Single- and Multiple-Ascending Dose Study in Healthy Male Volunteers","authors":"Tetsuya Koyama MS,&nbsp;Tatsunori Seki BSc","doi":"10.1002/jcph.70260","DOIUrl":"https://doi.org/10.1002/jcph.70260","url":null,"abstract":"<p>This first-in-human study evaluated the safety, pharmacokinetics (PK), food effect, and pharmacodynamics (PD) of AJM347, a novel orally active, selective α4β7 integrin antagonist, in healthy Caucasian and Japanese adult males. The study consisted of three parts. In the single-ascending dose (SAD) study (Part 1), AJM347 was administered in doses ranging from 6 to 2420 mg. The effect of food was evaluated in Part 2. In the multiple-ascending dose (MAD) study (Part 3), AJM347 was administered twice daily (200–800 mg) for 7 days. Single and multiple oral doses of AJM347 were safe and well tolerated. No changes in lymphocyte counts in whole blood and cerebrospinal fluid were observed. AJM347 was rapidly absorbed and the active metabolite, CAN2281, was rapidly formed. Administration of AJM347 after meals achieved higher trough concentrations of CAN2281 compared with administration under fasted conditions. AJM347 rapidly and dose-dependently inhibited mucosal addressin cell adhesion molecule-1 binding to CD4+ T cells. Doses ≥200 mg twice daily maintained &gt;90% inhibition (α4β7 receptor occupancy) for up to 24 h. PD effects correlated well with plasma concentrations of the active metabolite CAN2281. AJM347 demonstrated a favorable safety profile, effective target engagement, and promising PK properties for oral administration. The timing of dosing relative to meals did not affect the safety or overall PK profiles, but postprandial administration led to higher trough concentrations, suggesting that dosing after meals may represent the optimal regimen for the continued clinical development of AJM347. Blood samples were collected to assess PK and PD (α4β7 receptor occupancy). Samples were also collected to measure lymphocyte counts in peripheral blood and cerebrospinal fluid (CSF).</p>","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"66 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcph.70260","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Factor XI Inhibition for Ischemic Stroke Secondary Prevention: Pharmacology, Clinical Evidence, and Future Directions","authors":"Federica Ferrari MD, MSc, PhD, FCP,&nbsp;Roberto Federico Villa MD, MSc, FRSM","doi":"10.1002/jcph.70266","DOIUrl":"https://doi.org/10.1002/jcph.70266","url":null,"abstract":"<p>Ischemic stroke remains a leading cause of death and disability worldwide, and bleeding (particularly intracranial hemorrhage) continues to limit conventional antithrombotic therapy in secondary prevention, even with direct oral anticoagulants. Factor XI (FXI) has emerged as a promising target: it amplifies thrombin generation and stabilizes pathological thrombi while contributing only marginally to physiological hemostasis, as illustrated by the mild bleeding phenotype of congenital FXI deficiency. This biological dissociation underpins the concept of hemostasis-sparing anticoagulation. Three pharmacological classes are being studied, with distinct pharmacokinetic, pharmacodynamic, and drug-drug interaction profiles: small-molecule oral FXIa inhibitors (asundexian and milvexian), FXI antisense oligonucleotides (fesomersen), and monoclonal antibodies targeting FXI/FXIa (abelacimab and osocimab). Oral small molecules offer rapid, reversible target engagement particularly suited to chronic cerebrovascular prevention. While phase II trials (PACIFIC-Stroke, AXIOMATIC-SSP) showed neutral primary endpoints with reassuring safety, the phase III OCEANIC-STROKE trial demonstrated that asundexian 50 mg once daily, added to antiplatelet therapy, reduced recurrent ischemic stroke by 26% (HR 0.74; 95% CI 0.65–0.84) without significant bleeding excess in non-cardioembolic stroke; the ongoing LIBREXIA-STROKE is testing milvexian 25 mg twice daily in a similar setting. Conversely, OCEANIC-AF showed that FXIa inhibition alone is insufficient versus apixaban in atrial fibrillation, indicating dependence upon clinical setting and suggesting the need for a precision-medicine approach integrating clinical, imaging, and biomarker-based patient stratification. This narrative review integrates pathophysiological rationale, comparative pharmacology of all FXI-targeting classes, trial evidence, and patient stratification, providing an up-to-date reference for FXI/FXIa inhibition in secondary ischemic stroke prevention.</p>","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"66 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcph.70266","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148754157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"PBPK Modeling of Esomeprazole to Support Adolescent Pharmacokinetic Extrapolation and Label Extension in Chinese Patients With Gastroesophageal Reflux Disease (GERD)","authors":"Yuwen Jin MS,&nbsp;Junjie Ding PhD,&nbsp;Xiaohan Hua MS,&nbsp;Wei Duan MS,&nbsp;Mo Chen MS,&nbsp;Zhaohui Zhou MD,&nbsp;Ramesh V Pandherpur MBBS,&nbsp;Jin Dong PhD,&nbsp;Sharma Pradeep PhD,&nbsp;Peiming Ma PhD,&nbsp;Weifeng Tang PhD,&nbsp;Diansong Zhou PhD","doi":"10.1002/jcph.70255","DOIUrl":"10.1002/jcph.70255","url":null,"abstract":"<p>Esomeprazole, a proton pump inhibitor (PPI), is widely approved for gastroesophageal reflux disease (GERD) in adults and pediatrics globally, but prior to December 2022, its oral tablets (20 and 40 mg) were approved only for adults in China. To address unmet needs in Chinese adolescents aged 12–17 years, physiologically based pharmacokinetic (PBPK) modeling was employed to extrapolate data and support label extension, leveraging similarities in GERD pathophysiology and PK/PD relationships across ages and ethnicities.</p><p>A PBPK model was developed for esomeprazole to capture the enteric-coated formulation's pharmacokinetics. The model was validated against clinical PK studies in Caucasian, Japanese, and Chinese adults and/or adolescents, demonstrating good predictions of concentration–time profiles and area under the curve (AUC) for CYP2C19-specific genotypes as well as overall populations across these ethnic groups. All predicted-to-observed ratios for AUC fell within 0.5- to 2.0-fold, with 14 out of 18 predictions within the 0.67- to 1.5-fold. This robust validation enabled the model's application to predict PK in Chinese adolescents.</p><p>PBPK predictions for Chinese adolescents indicated that steady-state AUC for 20- and 40-mg doses was comparable to that in Japanese adolescents and slightly higher than in Caucasian adolescents. By integrating an established PK/PD relationship between AUC and the percentage of time with intragastric pH &gt;4, once-daily doses of 20 or 40 mg were justified, achieving adequate acid suppression with a favorable safety profile. This PBPK-informed extrapolation was accepted by China's National Medical Products Administration (NMPA), enabling GERD indication extension to adolescents.</p>","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"66 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148727296","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bayesian-Estimated Vancomycin AUC24 as a Near-Term Renal Risk Signal after Therapeutic Drug Monitoring: A Multicenter Cohort Study","authors":"Tran Van Anh BPharm, MSc,&nbsp;Bui Thi Tham BPharm, PhD,&nbsp;Tran Thi Ngan BPharm, PhD,&nbsp;Nguyen Duc Long, BPharm,&nbsp;Nguyen Huong Giang BPharm, MSc,&nbsp;Nguyen Hoang Anh BPharm, PhD,&nbsp;Vu Dinh Hoa BPharm, PhD,&nbsp;Hoang Van Dung MD, PhD,&nbsp;Nguyen Thi Thu Phuong MD, PhD","doi":"10.1002/jcph.70265","DOIUrl":"10.1002/jcph.70265","url":null,"abstract":"<p>Vancomycin therapeutic drug monitoring has moved toward area under the concentration–time curve (AUC)-guided dosing, but the clinical meaning of a Bayesian-estimated AUC generated at an individual monitoring episode remains uncertain when renal clearance may already be changing. We conducted a retrospective multicenter cohort study using inpatient dosing, pharmacy, therapeutic drug monitoring, and laboratory data from two hospitals in Hai Phong, Viet Nam, between 2019 and 2025. The analysis included 898 adult index vancomycin monitoring episodes with valid Bayesian-estimated AUC24 and sufficient serum creatinine data to ascertain acute kidney injury (AKI) within 48 h. AUC24 was estimated within the institutional Bayesian monitoring workflow using SmartDoseAI, with BestDose version 2.4.3 used as an independent pharmacokinetic cross-check in selected clinically uncertain episodes. AKI occurred in 84 episodes (9.4%). Higher continuous AUC24 was associated with AKI in the minimally adjusted model (odds ratio, 1.16 per 100 mg·h/L; 95% confidence interval, 1.02–1.33; <i>P</i> = .023), whereas categorical AUC contrasts were imprecise. The association attenuated after exclusion of 23 episodes with possible pre-existing AKI before the index monitoring episode (odds ratio, 1.12; 95% confidence interval, 0.96–1.31; <i>P</i> = .159), and restricted cubic spline modeling did not identify a distinct nonlinear threshold. Bayesian-estimated AUC24 at monitoring may therefore be most useful as a near-term renal risk signal that integrates vancomycin exposure with evolving renal clearance, rather than as a standalone causal toxicity threshold.</p>","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"66 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148727363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, Tolerability, and Pharmacokinetics of Oral Camlipixant: A Randomized First-In-Human Study Using Single and Multiple Ascending Doses","authors":"Nathalie Chauret MSc,&nbsp;Denis Garceau PhD,&nbsp;Laurent Harvey MSc,&nbsp;Zelie Bailes MSc,&nbsp;Elizabeth A. Duncan MD, PhD,&nbsp;Rhian McNaughton PhD,&nbsp;Miren Zamacona PhD","doi":"10.1002/jcph.70253","DOIUrl":"10.1002/jcph.70253","url":null,"abstract":"<p>Camlipixant is a highly selective P2X3 receptor antagonist with demonstrated efficacy in pre-clinical models of evoked cough. We report the safety, tolerability, and pharmacokinetics of camlipixant in healthy participants. This Phase 1, double-blind, randomized study evaluated single ascending doses (SAD; 50/100/200/400/800/1200 mg) and multiple ascending doses (MAD; 100/200/400 mg, twice daily [BID]) of oral camlipixant versus placebo. Ninety participants were included (SAD n =  60; MAD n =  30). Treatment-emergent adverse event (TEAE) incidence was similar between camlipixant (32/72) and placebo (9/18). TEAEs were mostly mild (83%), and the most common with camlipixant was dysgeusia, primarily at doses ≥400 mg (n =  13), versus 50–200 mg (n =  1). Camlipixant was rapidly absorbed (time to maximum plasma concentration SAD: 0.77–2.29 h; MAD: 0.50–2.00 h), with a short half-life (SAD 4.28–6.71 h; MAD 7.60–8.39 h). In both cohorts, maximum plasma concentration (C_max) increased proportionally with dose. The area under the curve extrapolated to infinity (AUC_0–∞) increased proportionally with dose in the SAD cohort; the increase was slightly supra-proportional in the MAD cohort (steady state reached on Day 2). The geometric mean apparent volume of distribution ranged from 44.9 to 70.2 L and clearance from 5.7 to 10.4 L/h in the SAD cohort. Pharmacokinetics were unaffected by food (geometric mean fed/fasted ratio C_max 91.4% [90% confidence interval, CI, 69.8–119.6]; AUC_0–∞ 105.5% [90% CI, 89.8–124.0]). In summary, camlipixant was well tolerated, with pharmacokinetics supporting BID dosing and further clinical development for refractory chronic cough.</p>","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"66 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcph.70253","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148708182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"FDA's Approval Summary of the First Biosimilar to Natalizumab for the Treatment of Multiple Sclerosis and Crohn's Disease","authors":"Poonam R. Delvadia PhD,&nbsp;Anantha Ram Nookala PhD,&nbsp;Gopichand Gottipati PhD,&nbsp;Sreedharan Sabarinath PhD,&nbsp;Ramana S. Uppoor PhD,&nbsp;Mehul U. Mehta PhD,&nbsp;Xiulian Du PhD,&nbsp;Yow-Ming C. Wang PhD,&nbsp;Milos Dokmanovic PhD,&nbsp;Riley Myers PhD,&nbsp;Jessica Stevens MD,&nbsp;Laura Baldassari MD, MHS,&nbsp;Paul Lee MD, PhD,&nbsp;Laura Jawidzik MD, FAAN,&nbsp;Sandhya Apparaju PhD,&nbsp;Suna Seo MD, MSc,&nbsp;Nina N. Brahme PhD, MPH,&nbsp;Sarah J. Schrieber PharmD","doi":"10.1002/jcph.70257","DOIUrl":"10.1002/jcph.70257","url":null,"abstract":"<p>The development and approval of biosimilars are imperative for improving patient access to safe and effective treatments. This article summarizes the regulatory approval for Tyruko, the first FDA-approved biosimilar for natalizumab for the treatment of multiple sclerosis and Crohn's disease. Biosimilarity between the proposed biosimilar and the reference product was demonstrated through a comprehensive comparative assessment that included structural and functional characterization, pharmacokinetics (PK)/pharmacodynamics (PD) data, immunogenicity, and safety. The PD assessment incorporated a panel of biomarkers indicative of target engagement and downstream biological responses. The current case underscores the importance of the 351(k) pathway and highlights how the PD-based approach, in conjunction with comparative analytical assessments and PK data, supported the approval of the biosimilar through a study design relying on fewer subjects and a shorter duration compared to an efficacy study.</p>","PeriodicalId":22751,"journal":{"name":"The Journal of Clinical Pharmacology","volume":"66 8","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148702216","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}