Advances in Therapy最新文献

{"title":"Five Data-Informed Principles for Advancing Inclusive Research in Clinical Trials: A Pharma Perspective","authors":"Spencer L. James,&nbsp;Shalini Hede,&nbsp;Altovise T. Ewing-Crawford,&nbsp;Ruma Bhagat,&nbsp;Nicole Richie,&nbsp;Mitchell D’Rozario,&nbsp;Pierre Theodore,&nbsp;Bea Lavery,&nbsp;Sarah Bentouati,&nbsp;Assaf P. Oron,&nbsp;Catherine W. Gillespie,&nbsp;Cleo A. Ryals,&nbsp;Megan H. Bair-Merritt,&nbsp;Johanna Chesley,&nbsp;Evelyn Jiagge,&nbsp;Bruno Jolain","doi":"10.1007/s12325-025-03283-8","DOIUrl":"10.1007/s12325-025-03283-8","url":null,"abstract":"<div><p>Advancing inclusive research (AIR) in clinical trials requires frameworks and metrics for assessing real-world data and measuring population science. Because different factors drive health inequities and variables in measuring population science, relying on one metric for measuring progress may have limitations. Five principles (5Ps) are proposed for AIR globally that form the basis for a data-informed framework to measure and systematically define inclusive research to ensure rigor and benchmarking within organizations and across the broader sector. The first principle addresses biological, genetic, and population science considerations and their responsible use as data elements. The second principle pertains to using data to inform global region, country, and site placement, which includes geographical proportionality in trial enrollment, enabled access and commercialization strategies, and representative real-world demographic representation. The third principle is developing a data-informed and user-informed approach to end-to-end inclusive trial design. The fourth principle integrates patient-reported data collection standards and initiatives supporting complete and consistent clinical trial collection. The fifth principle enables trial access by demonstrating trustworthiness, improving patient navigation, and providing assistance programs. These 5Ps can be used as an end-to-end measurable framework using reference metrics, reproducible data, and methodologies for AIR in clinical development.</p><p>Infographic available for this article.</p><div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 10","pages":"4727 - 4740"},"PeriodicalIF":4.0,"publicationDate":"2025-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03283-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758948","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Long-Term Safety and Efficacy of Pemafibrate to Treat Hyperlipidemia: Post-marketing Surveillance Over a 24-Month Observation Period in Japan","authors":"Mao Watanabe,&nbsp;Michiko Nakanishi,&nbsp;Wataru Shingaki,&nbsp;Ryoji Gunji,&nbsp;Yuichi Makinose,&nbsp;Takashi Kanno,&nbsp;Shun Ishibashi","doi":"10.1007/s12325-025-03294-5","DOIUrl":"10.1007/s12325-025-03294-5","url":null,"abstract":"<div><h3>Introduction</h3><p>Pemafibrate was well tolerated and effective in clinical trials that led to its approval to treat hyperlipidemia. However, these clinical trials typically have limitations and may not sufficiently assess the performance of pemafibrate in the real-world setting. Therefore, the aim of this study was to evaluate the long-term safety and efficacy of pemafibrate in patients with hyperlipidemia in Japan.</p><h3>Methods</h3><p>This was a prospective, multicenter, open-label, observational post-marketing surveillance (PMS) study. Patients with hyperlipidemia were observed for 24 months from the start of pemafibrate treatment. Safety evaluations included the incidence of adverse drug reactions (ADRs), subgroup analysis of ADRs, and changes in laboratory test values. Efficacy was determined by the changes in lipid test values from baseline.</p><h3>Results</h3><p>A total of 3672 cases were registered from 612 facilities in Japan. In the safety analysis, 68.1% of patients were male, mean age was 60.8 years, and 37.8% were switched to pemafibrate from other dyslipidemia agents. In total, 147 patients (4.07%) experienced ADRs; serious ADRs were reported in 8 patients (0.22%). The most common ADRs included abnormalities in laboratory tests (<i>n</i> = 60; 1.66%), hepatobiliary disorders (<i>n</i> = 24, 0.66%), musculoskeletal and connective tissue disorders (<i>n</i> = 14, 0.39%), and metabolic and nutritional disorders (<i>n</i> = 14, 0.39%). No incidents of rhabdomyolysis occurred, and 37 (1.02%) patients experienced rhabdomyolysis-related ADRs. Renal-related ADRs occurred in 13 patients (0.36%). When subdivided by patient background, the incidence of ADRs was significantly higher in patients aged ≥ 75 years than &lt; 75 years (<i>P</i> = 0.028). There were no significant differences in other subgroups. The mean percent change in mixed fasting and non-fasting triglyceride levels was − 35.2% (<i>P</i> &lt; 0.001). High- and low-density lipoprotein cholesterol levels both increased significantly.</p><h3>Conclusion</h3><p>This PMS study demonstrated the safety and efficacy of pemafibrate after long-term administration in patients with hyperlipidemia.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 10","pages":"4950 - 4963"},"PeriodicalIF":4.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03294-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Preferences for Injectable Lipid-Lowering Therapies in Japanese Patients with Atherosclerotic Cardiovascular Disease: Findings from a Japanese Cross-sectional Study","authors":"Mitsutoshi Toda,&nbsp;Kazuma Iekushi,&nbsp;Yuri Takahashi,&nbsp;Shun Kohsaka","doi":"10.1007/s12325-025-03321-5","DOIUrl":"10.1007/s12325-025-03321-5","url":null,"abstract":"<div><h3>Introduction</h3><p>Understanding patient preferences for injectable lipid-lowering therapies (LLTs) is crucial for optimizing adherence and outcomes for preventing atherosclerotic cardiovascular diseases (ASCVDs). This study aimed to quantify patient preferences for injectable LLTs among Japanese patients with ASCVDs.</p><h3>Methods</h3><p>This cross-sectional study was conducted from January to February 2024 using an online discrete choice experiment. Participants were recruited from the Rakuten Insight Disease Panel. A total of 59,611 individuals accessed the survey, and eligible adults aged ≥ 18 years with a history of dyslipidemia and currently receiving statin treatment were included. Participants were categorized into primary (<i>n</i> = 110) or secondary (<i>n</i> = 415) prevention groups based on their history of coronary artery disease or cerebral infarction.</p><h3>Results</h3><p>In the secondary prevention group, out-of-pocket costs was the most significant attribute (relative importance, 64.2%), followed by injection frequency (18.4%), administration method (12.1%), and efficacy (5.2%). Consistent attribute rankings were observed across subgroups. In the primary prevention group, out-of-pocket costs remained the most critical attribute (66.7%), followed by injection frequency (19.5%), efficacy (7.0%), and administration method (6.8%). After educational intervention, out-of-pocket costs remained the most important attribute (59.6%) in the secondary prevention group, followed by injection frequency (19.2%), administration method (11.8%), and efficacy (9.4%).</p><h3>Conclusion</h3><p>These findings highlight the importance of considering patient preferences in shared decision-making when selecting LLTs to enhance adherence and clinical outcomes.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 10","pages":"4933 - 4949"},"PeriodicalIF":4.0,"publicationDate":"2025-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03321-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144758950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Body Mass Index Progression, Development of Complications and Healthcare Costs Over 8 Years in UK Individuals Living With Overweight/Obesity","authors":"Luca Busetto,&nbsp;Silvia Capucci,&nbsp;João D. da Rocha Fernandes,&nbsp;Sara Holloway,&nbsp;Abd A. Tahrani,&nbsp;Andrew Thompson,&nbsp;Jonathan Pearson-Stuttard","doi":"10.1007/s12325-025-03285-6","DOIUrl":"10.1007/s12325-025-03285-6","url":null,"abstract":"<div><h3>Introduction</h3><p>A detailed understanding of the risk factors for and impacts of body mass index (BMI) progression in people living with obesity is vitally needed. In this retrospective observational study, we examined the relationships between BMI progression, obesity-related complications (ORCs) and healthcare costs in individuals living with overweight or obesity in the UK.</p><h3>Methods</h3><p>Data were from the Discover database of linked primary and secondary care records from 2.7 million individuals in North West London, UK. Included individuals were ≥ 18 years old, had a BMI of ≥ 25.0 kg/m² at index (date of first eligible BMI measurement during the study period: 1 January 2007 to 31 December 2019) and had no evidence of intentional weight loss. We examined BMI progression (increase) of ≥ 5% and ≥ 10% over 8 years in demographic and ORC subgroups, and compared ORCs and costs between groups with and without BMI progression.</p><h3>Results</h3><p>In total, 290,051 individuals were included, of whom 31.4% experienced BMI progression of ≥ 5% during follow-up, with most progression occurring from year 1 to year 3. Proportions of individuals with ≥ 5% BMI progression were highest in the following subgroups: 18–29 years (45.8%), 30–39 years (39.2%), polycystic ovary syndrome (41.4%), asthma (34.5%), depression (33.9%) and women (33.9%). Total annual healthcare costs per person per year were £1000 for those with no BMI progression, £1143 for those with 5 to &lt; 10% progression and £1251 for those with ≥ 10% progression. Groups with progression were more likely to develop ≥ 3 ORCs than those without.</p><h3>Conclusion</h3><p>Younger adults, women and people with specific ORCs were most likely to experience BMI progression, which was associated with increased health and economic burden. Targeting high-risk subgroups with interventions to prevent weight gain could limit the clinical and economic impacts of obesity.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 9","pages":"4626 - 4640"},"PeriodicalIF":4.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03285-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-World Effectiveness and Safety of Infliximab Biosimilar CT-P13 for Rheumatic Diseases: A National Observational Cohort Study (ReFLECT)","authors":"Hubert Marotte,&nbsp;Alain Cantagrel,&nbsp;Fabienne Coury,&nbsp;Thierry Schaeverbeke,&nbsp;Maryse Assing,&nbsp;Meriem Kessouri,&nbsp;Yves Brault,&nbsp;Bruno Fautrel","doi":"10.1007/s12325-025-03304-6","DOIUrl":"10.1007/s12325-025-03304-6","url":null,"abstract":"<div><h3>Introduction</h3><p>ReFLECT was a French multicenter, observational cohort study evaluating the effectiveness and safety of CT-P13, an infliximab (IFX) biosimilar, in a real-world setting. Here, we describe the results for patients with rheumatic disease.</p><h3>Methods</h3><p>Eligible patients with rheumatoid arthritis (RA), ankylosing spondylitis (AS), or psoriatic arthritis (PsA) were recruited and received intravenous CT-P13 induction and/or maintenance therapy. Patients were either naive to IFX (IFX-naive) or had been previously treated with IFX originator or another IFX biosimilar (IFX-switched). CT-P13 persistence (primary objective) was measured as a time-dependent variable during a 2-year follow-up period. Safety was also assessed.</p><h3>Results</h3><p>The patient population comprised 142 patients with RA (IFX-naive: <i>n</i> = 70; IFX-switched: <i>n</i> = 69; other [i.e., previously received IFX, but received another treatment before switching to CT-P13]: <i>n</i> = 3); 411 patients with AS (IFX-naive: <i>n</i> = 189; IFX-switched; n = 201; other: <i>n</i> = 21); and 96 patients with PsA (IFX-naive: <i>n</i> = 44; IFX-switched: <i>n</i> = 47; other: <i>n</i> = 5). After 2 years of follow-up, CT-P13 persistence rates were 49.6% (95% confidence interval [CI] 40.4–60.8%), 62.7% (95% CI 56.6–69.5%), and 73.0% (95% CI 62.7–85.1%) in patients with RA, AS, and PsA, respectively. CT-P13 persistence was greater for IFX-switched than IFX-naive groups in patients with RA (65.4% [95% CI 52.8–81.0%] vs. 33.3% [22.7–49.1%]) and AS (66.5% [95% CI 58.3–76.0%] vs. 56.6% [47.6–67.4%]) and was similar between IFX-switched and IFX-naive groups in patients with PsA (75.9% [95% CI 62.2–92.8%] vs. 72.0% [57.5–90.1%]). The main reason for CT-P13 discontinuation was loss of response (RA/AS/PsA) in both IFX-naive (38.6%/23.3%/22.7%) and IFX-switched 18.8%/18.4%/12.8%) groups. Among patients (RA, AS, and PsA), 52.1%, 57.9%, and 56.3%, respectively, reported ≥ 1 adverse event (AE), and 14.1%, 11.4%, and 10.4%, respectively, reported serious AEs.</p><h3>Conclusion</h3><p>After 2 years of follow-up, the effectiveness of intravenous CT-P13 was maintained in &gt; 65% of IFX-switched patients and CT-P13 induced effective therapeutic maintenance in IFX-naive patients. CT-P13 had an acceptable safety profile.</p><h3>Trial Registration</h3><p>ClinicalTrials.gov identifier: NCT02925338.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 9","pages":"4659 - 4680"},"PeriodicalIF":4.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03304-6.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726462","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Efficacy and Safety Maintained up to 3 Years in Adults with Paroxysmal Nocturnal Hemoglobinuria Receiving Pegcetacoplan","authors":"Carlos de Castro,&nbsp;Richard J. Kelly,&nbsp;Morag Griffin,&nbsp;Christopher J. Patriquin,&nbsp;Brian Mulherin,&nbsp;Britta Höchsmann,&nbsp;Veena Selvaratnam,&nbsp;Raymond Siu Ming Wong,&nbsp;Peter Hillmen,&nbsp;Regina Horneff,&nbsp;Uchendu O. Uchendu,&nbsp;Yiwei Zhang,&nbsp;Elena Surova,&nbsp;Johan Szamosi,&nbsp;Regis Peffault de Latour","doi":"10.1007/s12325-025-03310-8","DOIUrl":"10.1007/s12325-025-03310-8","url":null,"abstract":"<div><h3>Introduction</h3><p>Pegcetacoplan, the first C3 and C3b inhibitor for paroxysmal nocturnal hemoglobinuria (PNH), demonstrated efficacy and safety in C5 inhibitor-experienced and -naive patients in the phase 3 studies PEGASUS (NCT03500549) and PRINCE (NCT04085601), respectively. This integrated analysis of PEGASUS, PRINCE, and their subsequent open-label extension study (NCT03531255) evaluated pegcetacoplan long-term efficacy and safety.</p><h3>Methods</h3><p>Efficacy was assessed from pegcetacoplan initiation through 2.5 years (PRINCE) and 3 years (PEGASUS) by measuring hemoglobin, lactate dehydrogenase (LDH), absolute reticulocyte count (ARC), indirect bilirubin, and Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue scores. Transfusion avoidance and safety were assessed during pegcetacoplan monotherapy. Of 133 patients in PRINCE and PEGASUS, 114 enrolled in the extension. Most patients (PRINCE, 81.1%; PEGASUS, 75.0%) were transfusion dependent at trial entry and baseline hemoglobin was below normal.</p><h3>Results</h3><p>Pegcetacoplan markedly and rapidly (within 4 weeks) improved all efficacy measures, which stabilized close to (hemoglobin, FACIT-Fatigue) or within (LDH, ARC, indirect bilirubin) normal range for up to 3 years; annual transfusion avoidance rates were 79.5–86.4% in PRINCE and 71.2–79.2% in PEGASUS. No new safety concerns were identified over 3 years. Serious adverse events were reported in 73 (55.3%) patients, deemed pegcetacoplan related in 6 (4.5%) patients. Most injection site reactions were mild, and their incidence decreased over time. Five (3.8%) deaths occurred (none deemed pegcetacoplan related); 37 (28.0%) patients experienced clinically significant and laboratory-confirmed breakthrough hemolysis; 4 thrombotic events occurred in 3 (2.3%) patients; no meningitis cases were reported.</p><h3>Conclusion</h3><p>Pegcetacoplan efficacy and safety was sustained for up to 3 years in patients with PNH, with or without prior C5 inhibitor treatment, verifying the long-term favorable clinical profile of this proximal complement inhibitor.</p><h3>Trial Registration</h3><p>ClinicalTrials.gov NCT03500549 (PEGASUS), NCT04085601 (PRINCE), and NCT03531255 (307 OLE).</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 9","pages":"4641 - 4658"},"PeriodicalIF":4.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03310-8.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacokinetic Bioequivalence, Safety, and Immunogenicity of DMB-3115, an Ustekinumab Biosimilar, and EU- and US-Stelara in Healthy Adult Participants: A Randomized, Double-Blind, Single-Dose Study","authors":"Jun Morita,&nbsp;Rainard Fuhr,&nbsp;Thomas Koernicke,&nbsp;Naoki Cho,&nbsp;Thin Thin Mencarini,&nbsp;Hideki Fushimi","doi":"10.1007/s12325-025-03290-9","DOIUrl":"10.1007/s12325-025-03290-9","url":null,"abstract":"<div><h3>Introduction</h3><p>The aim of this study was to investigate the pharmacokinetic bioequivalence between DMB-3115 and ustekinumab (EU-Stelara or US-Stelara) as well as the safety and immunogenicity of these drugs in healthy adult participants.</p><h3>Methods</h3><p>This was a randomized, double-blind, three-arm parallel-group study. Healthy participants aged 18–55 years were randomly assigned in a 1:1:1 ratio to receive a single subcutaneous injection (45 mg) of either DMB-3115, EU-Stelara, or US-Stelara. Participants were stratified into two body weight groups (&lt; 80 vs. ≥ 80 kg). Participants were followed for 16 weeks. The primary pharmacokinetic (PK) endpoints were area under the concentration–time curve from time zero to infinity (AUC_inf), AUC from time zero to the time of the last quantifiable concentration (AUC_last), and maximum serum concentration (<i>C</i>_max). Immunogenicity was tested using antidrug antibody (ADA) assays.</p><h3>Results</h3><p>A total of 296 participants (<i>n</i> = 99 in the DMB-3115 group, <i>n</i> = 99 in the EU-Stelara group, and <i>n</i> = 98 in the US-Stelara group) received the study drug and were included in the safety analysis. Of these, one participant in the DMB-3115 group had no valid PK data and was excluded from the PK analysis. The 95% confidence intervals (CI) for the ratios of geometric least squares means (DMB-3115/EU-Stelara and DMB-3115/US-Stelara) of the primary PK endpoints (AUC_inf, AUC_last, and <i>C</i>_max) were within the prespecified bioequivalence range of 80–125%. Originally this study was designed for the comparison of EU and US Stelara with two formulations of DMB-3115. To avoid multiplicity, a 95% CI was chosen. After that, only one formulation was selected. However, overall design was not changed. Using a 95% CI provided a more stringent level for the bioequivalence evaluation and was acceptable for European Medical Agency and US Food and Drug Administration. The proportions of participants reporting any treatment-emergent adverse event (TEAE) were similar among the three groups. The most common TEAEs were headache, nasopharyngitis, back pain, diarrhea, and oropharyngeal pain. Most TEAEs were mild or moderate in severity, and no TEAEs led to study discontinuation. The incidences of participants with post-dose ADAs and neutralizing antibodies in DMB-3115 tended to be lower among the groups.</p><h3>Conclusion</h3><p>DMB-3115 was bioequivalent to both reference ustekinumab in terms of pharmacokinetic profile and showed similar safety and immunogenicity profile after a single subcutaneous injection in parallel groups of healthy adult participants.</p><h3>Clinical Trial Registration</h3><p>European Union Clinical Trials Register: number 2018-004033-33; date of registration 17 October 2018.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 9","pages":"4681 - 4695"},"PeriodicalIF":4.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03290-9.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726461","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Firsekibart, an Anti-interleukin-1β Monoclonal Antibody, in Healthy Chinese Participants: A Randomized, Double-Blind, Placebo-Controlled Phase 1 Study","authors":"Hongzhong Liu,&nbsp;Yuping Yuan,&nbsp;Wei Tian,&nbsp;Tianhong Luo,&nbsp;Qian Xu,&nbsp;Xiaoyan Zhu,&nbsp;Rui Chen","doi":"10.1007/s12325-025-03279-4","DOIUrl":"10.1007/s12325-025-03279-4","url":null,"abstract":"<div><h3>Introduction</h3><p>The pro-inflammatory cytokine interleukin-1β (IL-1β) is an important therapeutic target for treating autoinflammatory diseases. Firsekibart is a high affinity, fully human monoclonal antibody targeting IL-1β, which selectively binds to and neutralizes IL-1β. Here, we investigated the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of firsekibart administered as a single-dose, subcutaneous injection in healthy Chinese participants.</p><h3>Methods</h3><p>This first-in-human, double-blind, phase 1 trial of firsekibart included healthy Chinese participants (≥ 18 to ≤ 50 years old) divided into five dose-escalated groups: 0.3, 1.0, 2.0, 4.0, and 6.0 mg/kg. In each group, participants were randomized in a 3:1 ratio to receive firsekibart or placebo. The primary endpoint was the safety and tolerability, primarily assessed by monitoring adverse events (AEs). Secondary endpoints included the evaluation of immunogenicity, PK, and PD.</p><h3>Results</h3><p>A total of 40 participants were enrolled in the study, receiving either firsekibart (<i>n</i> = 30) or placebo (<i>n</i> = 10); all participants completed the study. Treatment-emergent AEs (TEAEs) occurred in 86.7% of participants receiving firsekibart and 90.0% receiving placebo. There were no reports of grade ≥ 3 TEAEs, serious AEs, or TEAEs leading to study withdrawal or death. The incidence of TEAEs in the firsekibart group was not dose dependent. No PK/PD changes or safety events related to immunogenicity were observed. Serum concentration of firsekibart at each sampling timepoint increased proportionally with dose (0.3–6.0 mg/kg). The area under the concentration–time curve from zero to infinity (AUC_0–∞) showed a linear relationship with the dose of firsekibart. Overall, there were no treatment or dose-related trends observed in PD parameters, and no significant correlation was found between PK parameters and total serum IL-1β levels.</p><h3>Conclusion</h3><p>Firsekibart had an acceptable safety profile and was well tolerated in healthy Chinese participants across all investigated doses, supporting future investigation of firsekibart as a potential treatment option for inflammatory diseases.</p><h3>Trial Registration</h3><p>ClinicalTrials.gov NCT04337437 (retrospectively registered on April 7, 2020).</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 9","pages":"4611 - 4625"},"PeriodicalIF":4.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03279-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706001","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of XSB-001 (Ranibizumab Biosimilar) Physicochemical and Biological Stability in Prepared Syringes for Intravitreal Injection","authors":"Robert Björnestedt,&nbsp;Sean Waters,&nbsp;Aušrinė Paišytė,&nbsp;Fabricio Furlan,&nbsp;Christian Wanner","doi":"10.1007/s12325-025-03319-z","DOIUrl":"10.1007/s12325-025-03319-z","url":null,"abstract":"<div><h3>Introduction</h3><p>Vascular endothelial growth factor A (VEGF-A) is a key driver of neovascularization and vascular permeability in retinal diseases such as neovascular age-related macular degeneration and diabetic macular edema. XSB-001 (Ximluci^<b>®</b><b>)</b>, a ranibizumab biosimilar has demonstrated equivalent safety, efficacy, and biological activity to reference ranibizumab, supporting its use in these indications.</p><h3>Methods</h3><p>This study evaluates the extended physicochemical and biological stability of XSB-001 under real-world handling conditions for 30 days. XSB-001 was stored at 5 ± 3 °C in vials and prepared into two syringe types. Samples were maintained under monitored conditions for 30 days, with a subset exposed to room temperature, humidity and indoor lighting or protected from light for 48 h.</p><h3>Results</h3><p>Across all test conditions, XSB-001 maintained expected liquid physical state, clarity, and color within specification limits, besides charge variants. High monomer purity (99.6%), high molecular weight species (0.4%) and low molecular weight species (&lt; 0.35%) were observed, satisfying all required criteria. Size exclusion–high-performance liquid chromatography (SE-HPLC) analysis confirmed monomer content at 99.6%, surpassing the ≥ 99.0% requirement. Reverse-phase high-performance liquid chromatography (RP-HPLC) showed consistent main peak purity of 97.3%, exceeding the ≥ 97.0% criterion. Strong cation exchange high-performance liquid chromatography (SCX-HPLC) recorded main peak values between 96.5 and 96.6%, meeting the ≥ 96.5% threshold. Acidic (1.7%) and basic species (1.6–1.7%) were consistently within specification limits (≤ 2.5%). Sub-visible particulate analysis indicated particle counts within acceptable limits. Protein concentration was stable across storage conditions, ranging from 9.9 to 10.4 mg/ml.</p><h3>Conclusion</h3><p>These findings support the extended stability of XBS-001 stored in unopened vials and subsequently prepared syringes (and independent of syringe type), optimizing patient care and treatment management efficiency.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 9","pages":"4597 - 4610"},"PeriodicalIF":4.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03319-z.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144706000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Key Learnings from Clinical Research and Real-World Evidence on Asfotase Alfa Effectiveness in Hypophosphatasia: 10 Years Post-Approval","authors":"Aliya A. Khan,&nbsp;Eric T. Rush,&nbsp;Craig Wakeford,&nbsp;Daniel Staub,&nbsp;Maria Luisa Brandi","doi":"10.1007/s12325-025-03309-1","DOIUrl":"10.1007/s12325-025-03309-1","url":null,"abstract":"<div><p>First reported in 1948, hypophosphatasia (HPP) is a rare systemic disease caused by deficient activity of tissue-nonspecific alkaline phosphatase (ALP) enzyme. Patients with HPP experience skeletal and dental manifestations such as rickets/osteomalacia, fractures, pseudofractures, and premature tooth loss, as well as nonskeletal symptoms such as pain and muscle weakness, which result in impaired mobility and poor quality of life. For decades, no specific treatment was available for HPP and the disease was often fatal in infants. Asfotase alfa is a tissue-nonspecific ALP enzyme replacement therapy (ERT) that received first regulatory approval in 2015 in Japan, the European Union, and the United States for the treatment of HPP. This review draws from clinical trial findings, real-world evidence, and relevant case study data demonstrating the safety and effectiveness of asfotase alfa in improving a broad range of skeletal and nonskeletal manifestations in both pediatric and adult patients. Asfotase alfa has been shown to be well tolerated, with manageable side effects. Further, asfotase alfa treatment has improved survival and respiratory outcomes, skeletal outcomes, physical and motor function, pain, disability, and quality of life in patients with HPP. This evidence-based review aims to generate a foundation for improving the understanding of disease pathophysiology, hence enhancing the effectiveness of ERT in patients with HPP.</p></div>","PeriodicalId":7482,"journal":{"name":"Advances in Therapy","volume":"42 9","pages":"4270 - 4299"},"PeriodicalIF":4.0,"publicationDate":"2025-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://link.springer.com/content/pdf/10.1007/s12325-025-03309-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144726460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}