Therapeutic innovation & regulatory science最新文献

{"title":"Therapeutic Horizon in Multiple Myeloma: Analysis of the Emerging Landscape of Clinical Trials.","authors":"Marina Alacoque Rodrigues, Cristiane Aparecida Menezes de Pádua, Paula Lana de Miranda Drummond, Jéssica Soares Malta, Adriano Max Moreira Reis","doi":"10.1007/s43441-026-00971-7","DOIUrl":"https://doi.org/10.1007/s43441-026-00971-7","url":null,"abstract":"<p><strong>Background: </strong>Emerging therapies for multiple myeloma (MM) have significantly improved patient outcomes extending survival and advancing treatment toward more targeted, effective, and less toxic approaches. However, the disease remains incurable.</p><p><strong>Objectives: </strong>Analyze the therapeutic landscape of MM by evaluating drug candidates in clinical trials from 2014 to 2024.</p><p><strong>Methods: </strong>Data were extracted from ClinicalTrials.gov (CTG) and Cortellis Drug Discovery Intelligence (CDDI), including active and completed studies with results on newly diagnosed and refractory MM. Joinpoint regression models estimated Annual Percent Changes (APCs) and Average Annual Percent Changes (AAPC). Data were examined by clinical trial characteristics, targeting strategies, and potential impact on treatment advancements.</p><p><strong>Results: </strong>A total of 1091 trials from CDDI and 1947 from CTG were screened, yielding 365 studies eligible for detailed analysis. Phase I trials were the most common (n = 182; 49.9%), and biologic agents represented the majority of the investigational therapies (n = 251; 68.8%). Among intervention types, cell therapies were predominant (n = 171; 46.8%), with CAR-T products targeting BCMA (n = 107), CD19 (n = 16), and GPRC5D (n = 12) emerging as the most studied in recent years. Before the joinpoint, the number of active trials grew by 1.86% per year (95% CI: 1.67-2.06), corresponding to an average increase of 11.9 studies annually. After the joinpoint, growth accelerated to 3.69% per year (95% CI: 3.19-4.19), equivalent to 26.5 additional trials each year. Across the entire study period, the weighted average annual percentage change (AAPC) was 2.63%.</p><p><strong>Conclusion: </strong>The rise in MM clinical trials highlights a shift toward biologic therapies, particularly immunotherapies and gene therapies like CAR-T.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Advancing Wider Implementation of Multi-regional Clinical Trials in East Asia.","authors":"John H Skerritt, Irene Chan, Aloka Chakravarty","doi":"10.1007/s43441-026-00981-5","DOIUrl":"https://doi.org/10.1007/s43441-026-00981-5","url":null,"abstract":"<p><p>The ICH E17 guideline is intended to promote the effective and efficient use of multi-regional clinical trials in simultaneous global medicines development, contributing to faster patient access. However, its uptake has been slower than hoped, and some regulators often require local (national) clinical trial data for regulatory submissions. This review examines the extent of ethnic (country of origin) influences on pharmacokinetic (PK) or pharmacodynamic (PD) profile of drugs, with a focus on East Asian countries. We conclude that clinically significant ethnic differences are likely to be less common for many newer therapeutics than older drugs, especially those older small-molecule drugs with low therapeutic indices. Major source of ethnic differences in drug PK or PD are due to differences in the allelic frequencies of particular genes for metabolizing enzymes and other drug targets or receptors, respectively. The default approach for conducting clinical trials for products intended for global markets should be to assess safety and efficacy through multi-regional clinical trials and requirements for country-specific enrolment in trials infrequently justifiable only on scientific grounds.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147843168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacovigilance Data From Digital Health Systems: Regulations, Implications, and Opportunities-A TransCelerate Perspective.","authors":"James Whitehead, Rajesh Ghosh, Anna Monaco, Jackie Grissinger, Inessa Neyman, Tom Umrath, Clint Craun","doi":"10.1007/s43441-025-00907-7","DOIUrl":"https://doi.org/10.1007/s43441-025-00907-7","url":null,"abstract":"<p><p>Digital health technologies (DHTs) represent a clear potential to advance the science of pharmacovigilance and promote patient safety. A project was created to assess the current landscape for use of DHTs and identify opportunities to use DHTs in fulfilling these objectives. TransCelerate Biopharma Inc, a non-profit launched in 2012 to accelerate and enhance research of human medicines, led an assessment of digital health in pharmacovigilance focused on the global regulatory landscape. This was achieved through first identifying and forming a glossary of applicable terminology and compiling an index of related regulations, guidelines, and source materials from global health authorities. Using this information, a regulatory landscape assessment was performed, and an industry survey designed. Both outputs indicated that the use of DHTs in pharmacovigilance applications in the pharmaceutical industry is in early development stages for both regulations and real-world utilization. This insight led TransCelerate to develop a tool that would enable a robust exploration of individual DHTs used in the post approval setting through the lens of pharmacovigilance professionals, through proposed considerations for enhancing product safety. This work is intended to positively support the industry in understanding the use and impact of DHTs on pharmacovigilance and readiness. There remains an opportunity to set forth guiding principles and a framework, in collaboration with regulators, healthcare professionals, systems, and patients for DHTs to advance the science of pharmacovigilance.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":""},"PeriodicalIF":1.9,"publicationDate":"2026-05-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147821053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating Post-Progression Survival in the Context of Progression-Free Survival Benefits: A Revisit of the CodeBreaK200 Design.","authors":"Zhoujingpeng Wei, Yuanyuan Han, Luoying Yang, Pourab Roy, Chunsheng He, Liangang Liu, Shu-Pang Huang, Hsin-Ju Hsieh","doi":"10.1007/s43441-026-00924-0","DOIUrl":"10.1007/s43441-026-00924-0","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Overall survival (OS) remains the gold-standard endpoint in oncology trials, while progression-free survival (PFS) is a widely used surrogate endpoint that captures tumor progression earlier. However, an increase in PFS has not necessarily led to an improvement in OS (Reck M, 2009). The recent CodeBreaK 200 trial, a randomized, open-label Phase 3 study evaluating sotorasib versus docetaxel as the control arm for previously treated metastatic NSCLC with KRAS G12C mutations (Langen et al., 2023), demonstrated a significant improvement in PFS with sotorasib. However, there was no significant difference in OS between the sotorasib and docetaxel arms, suggesting that PFS may not fully capture the long-term impact of treatment. This discordance led the Oncologic Drugs Advisory Committee (ODAC) to recommend against granting full approval to sotorasib, despite the committee expressing optimism about the drug's potential efficacy (FDA ODAC meeting minutes, 10/05/2023).&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Purpose: &lt;/strong&gt;In this paper, we aim at identifying the factors that contribute to the discordance between the PFS and OS, especially those that lead to insignificant OS improvement in the presence of the significant benefits to PFS. More importantly, we propose guidance on how to adjust or plan for such factors during the study design in order to better demonstrate the treatment benefit to OS assuming the drug is efficacious.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;We proposed to use post-progression survival (PPS), which is defined as the difference between OS and PFS. We developed a flexible parametric simulation framework centered on PPS to quantify how various design factors impact OS given PFS is significant. Based on the simulated data under various scenarios, we investigated the impact of several factors, including censoring informativeness, crossover rates, subsequent therapy access, and improved treatment effect. Moreover, we revisited CodeBreaK200 design as a case study through extracting information from the CodeBreaK200 protocol and digitizing Kaplan Meier curves from published FDA documents.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Our simulations reveal several factors that may lead to the discrepancy between the PFS and OS. First, allowing control-arm patients to crossover to the experimental therapy may lengthen their PPS, thereby shrinking the OS difference between the experimental treatment and control arm. Secondly, permitting both arms to access subsequent treatments similarly narrows the PPS difference. Even a stronger treatment effect that extends PPS in both arms further obscures the OS advantage of the experimental treatment arm. Finally, informative censoring (e.g., due to unbalanced early dropout between the experimental and control arms) may bias estimates of both PFS and OS. When the PFS benefit in the experimental arm is overestimated due to informative censoring, the apparent discordance between PFS and OS may be exaggerated. A ","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"847-859"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146158442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the Contribution of Components in Late-Phase Oncology Trials: A Roadmap of Key Approaches.","authors":"Xiaowen Tian, Kristine Broglio, Di Ran, Jianliang Zhang, Xia Li","doi":"10.1007/s43441-026-00937-9","DOIUrl":"10.1007/s43441-026-00937-9","url":null,"abstract":"","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"703-712"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147373198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Incorporating Patient Perspectives into Structured Benefit-Risk Assessment: A Drug Development Framework Recommendation.","authors":"Emuella Flood, Niklas Karlsson, Jennifer Ostridge, Bistra Kirova, Tim Sullivan, György Zörényi, Barbara Valastro, Jiyoon Park","doi":"10.1007/s43441-026-00940-0","DOIUrl":"10.1007/s43441-026-00940-0","url":null,"abstract":"<p><p>Regulatory agencies have been promoting the incorporation of the patient perspective into benefit-risk assessment to better align regulatory decisions with patients' needs and priorities. Currently, benefit-risk assessments for regulatory submissions primarily capture the patient perspective through patient-reported outcome data from clinical trials. However, there is a push for a more systematic approach to capturing the patient perspective in benefit-risk assessment and decision-making throughout the drug development life cycle. Although different guidelines and frameworks have been developed, consensus on how to systematically incorporate the patient perspective into structured benefit-risk (sBR) assessment remains elusive. In 2023, Sullivan et al. published an sBR assessment framework that was developed to enhance systematic and collaborative decision-making throughout a drug life cycle. Here we propose how this sBR assessment framework could be expanded, committing to a patient-centered approach by considering the patient perspective at every step of drug development. These recommendations aim to put patients at the center of drug development, ultimately leading to better treatment outcomes and improved lives.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"713-724"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147378595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancing Data Quality in Clinical Trials: Cross-Company Validation of the Open-Source Clinical Trial Anomaly Spotter (CTAS).","authors":"Pekka Tiikkainen, Frederik Collin, Björn Koneswarakantha","doi":"10.1007/s43441-026-00950-y","DOIUrl":"10.1007/s43441-026-00950-y","url":null,"abstract":"<p><strong>Background: </strong>Current ICH guidelines, e.g. ICH E6 (R3), advocate a risk-based statistical review of clinical trial data to identify anomalies. The open-source R package, clinical trial anomaly spotter (CTAS) has been developed by Bayer and the Intercompany Quality Analytics (IMPALA) consortium, helps detect inconsistencies in subject time series data at both site and subject levels, facilitating timely intervention.</p><p><strong>Methods: </strong>CTAS analyzes time series of equal length. Each subject-level time series is summarized as six optional scalars: mean, standard deviation, range, relative unique value count, autocorrelation and local outlier factor. To detect site-level anomalies, sites can be scored using 3 different scoring methods. The performance of the CTAS algorithm was tested using simulations, artificially introducing site anomalies of various types and degrees into clinical trial data sets.</p><p><strong>Results: </strong>We found that CTAS can reliably detect site anomalies depending on the degree of the anomaly introduced. Less complex anomalies such as mean were easier to detect than complex outlier such as local outlier factor. The three scoring methods differed in their ability to detect anomalous sites with a small number of patients and their false positive rates.</p><p><strong>Conclusions: </strong>CTAS is a valuable tool for timely detection of outliers in clinical data, suitable for integration into risk-based strategies. Choosing the appropriate site anomaly scoring method is crucial for handling sites with fewer subjects effectively.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"643-653"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13110196/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147445344","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Quantifying Eligibility Pattern Shifts: a Data-Driven Paradigm for Early Risk Detection in Clinical Trials.","authors":"Atanu Bhattacharjee, Ayon Mukherjee","doi":"10.1007/s43441-026-00918-y","DOIUrl":"10.1007/s43441-026-00918-y","url":null,"abstract":"<p><p>Traditional Risk-Based Monitoring (RBM) strategies emphasise key risk indicators and site-level performance metrics but seldom address the heterogeneity of patient eligibility profiles. We present a data-driven framework that captures temporal and inter-site shifts in baseline inclusion characteristics. Central to this framework are two new metrics-Borderline Inclusion Index and Eligibility Distribution Divergence-that quantify departures from expected enrolment patterns. A Bayesian composite score synthesises these indicators to prioritise oversight actions. Through simulation experiments and a worked case study, we show that monitoring eligibility pattern shifts offers an early warning signal of operational or scientific risk and strengthens overall trial integrity. We operationalize the framework through an interactive Shiny web application that computes indicator-specific posteriors, generates composite site risk scores, and provides visual decision-support for centralized RBM implementation.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"798-812"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13110207/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Patent Analysis Perspectives on China's Orphan Drug R&D: Status and Technology Characteristics.","authors":"Yang Jiao, Fangzhe Yuan, Tianyu Liu, Jiajia Han, Jingchun Sun, Shuzhen Chu, Shuxiang Li","doi":"10.1007/s43441-026-00927-x","DOIUrl":"10.1007/s43441-026-00927-x","url":null,"abstract":"<p><strong>Background: </strong>Rare diseases present urgent public health challenges requiring coordinated global efforts. This study analyzes China's orphan drug innovation landscape through patent applications (1995-2023) to identify R&D patterns and policy implications.</p><p><strong>Methods: </strong>We analyzed 323 Patent Cooperation Treaty applications from Chinese entities using IPC classification and bipartite network modeling. Data from World Intellectual Property Organization were retrieved via PatSnap, with diseases mapped to China's Rare Disease Catalogues (207 conditions). Network metrics quantified disease-technology linkages.</p><p><strong>Results: </strong>Three key findings emerged: (1) Patent filings surged 58.2% (188 patents) during 2018-2023, coinciding with China's regulatory reforms; (2) Innovation concentrated in oncology/neurology (34.3% patents cover 2 diseases), with 66.2% of catalogued diseases lacking patents; (3) Dominant technologies are small molecules and genetic therapies. Network analysis revealed an R&D ecosystem without a single dominant entity, alongside robust collaborative ties between Chinese and U.S. organizations.</p><p><strong>Conclusions: </strong>China's orphan drug innovation is expanding rapidly but remains uneven, concentrated in specific diseases and technological platforms. Policy interventions are needed to address therapeutic neglect through tiered incentives, dedicated funding for neglected diseases, and global partnerships to accelerate equitable treatment access.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"860-871"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146202802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Japan's Pharmaceutical Regulatory Reform to Overcome Drug Loss Issue.","authors":"Kiyohito Nakai","doi":"10.1007/s43441-026-00928-w","DOIUrl":"10.1007/s43441-026-00928-w","url":null,"abstract":"<p><p>In recent years, there has been a significant increase in \"drug loss\"-the absence of drugs on the Japanese market that are already approved in countries outside of Japan-primarily due to the lack of their development in Japan. There were 86 drugs approved in Europe and the United States for which development had not yet begun in Japan. Of these, 48 (56%) were what can be termed 'venture-developed' drugs, 40 (47%) were orphan drugs, and 32 (37%) were for pediatric use. The lack of availability of these drugs in Japan is a significant issue.In an attempt to address this drug loss issue, the Japanese Ministry of Health, Labour and Welfare (MHLW) decided to focus on and review Japan's pharmaceutical regulations, which were considered an important factor in the drug loss issue. The MHLW held a series of meetings to discuss possible changes in its policies and methods as potential solutions to the drug loss problem. MHLW issued several notifications and related Question and Answer (Q&A) communications about those discussions. Furthermore, MHLW made revisions to the Pharmaceutical and Medical Device Act that were enacted in May 2025.This manuscript summarizes the major outcomes of these activities, particularly the issues related to clinical trials and the orphan designation system, in terms of how they relate to the future of pharmaceutical regulation in Japan.</p>","PeriodicalId":23084,"journal":{"name":"Therapeutic innovation & regulatory science","volume":" ","pages":"612-616"},"PeriodicalIF":1.9,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146198028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}