Drugs in Research & Development最新文献

{"title":"A Bioequivalence Study of Recombinant Human Follicle-Stimulating Hormone Injection Versus Recombinant Human Follitropin For Injection in Healthy Chinese Adult Women.","authors":"Jigang Zhang, Mingjian Zhang, Wenyuan Xue, Yixin Zha, Shujing Jin, Tianhong Luo, Ying Ding, Weiwei Gao, Xueying Ding, Xiaoyan Zhu","doi":"10.1007/s40268-025-00513-w","DOIUrl":"https://doi.org/10.1007/s40268-025-00513-w","url":null,"abstract":"<p><strong>Background and objective: </strong>This study aimed to evaluate the bioequivalence of a novel prefilled recombinant human follicle-stimulating hormone (rh-FSH) injection (GenSci008) compared with the existing rh-FSH for injection (Jinfollin^®) in healthy Chinese adult women.</p><p><strong>Methods: </strong>This open-label, randomized, single-center, two-period, two-sequence crossover study involved 24 healthy female volunteers who received single subcutaneous doses of both formulations, separated by a 10-day washout period. Participants underwent pituitary down-regulation using Diphereline^® to minimize endogenous FSH levels. Pharmacokinetic parameters, including peak concentration (C_max), area under the drug-time curve from 0 to t (AUC_0-t), and AUC from 0 to infinity (AUC_0-∞) were measured, and bioequivalence was assessed based on the 90% confidence intervals (CIs) falling within the 80.00-125.00% range. Safety and immunogenicity were also evaluated.</p><p><strong>Results: </strong>The geometric mean ratios (GMRs) and 90% CIs for baseline-corrected AUC_0-t, AUC_0-∞, and C_max of the test formulation relative to the reference formulation were 99.99% (93.57-106.86), 102.70% (93.31-113.03), and 93.41% (87.77-99.41), respectively; all within the predefined bioequivalence range. Safety profiles were similar between the two formulations, with no suspected unexpected serious adverse reaction (SUSAR) identified.</p><p><strong>Conclusion: </strong>The novel prefilled rh-FSH injection (GenSci008) is bioequivalent to the reference formulation (Jinfollin^®), offering a user-friendly and precise alternative for subcutaneous administration in the treatment of infertility.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144621001","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":"In-Vitro Comparison of Physical Characteristics, Enzyme Content, and Release Kinetics of Pancreatic Enzyme Preparations Available in Europe and Canada.","authors":"Sven Hartmann, Jonas Rosendahl, Amy Todd, Emma Bennett-Huntley, J Enrique Domínguez-Muñoz","doi":"10.1007/s40268-025-00515-8","DOIUrl":"https://doi.org/10.1007/s40268-025-00515-8","url":null,"abstract":"<p><strong>Introduction: </strong>Commercially available pancreatic enzyme replacement therapy (PERT) preparations differ significantly in their physical and enzyme properties, raising concern about the interchangeability of these preparations. The current study aimed to compare various commercially available PERT in Europe and Canada for physical properties, enzyme content, enzyme activities, release characteristics, and compliance with the label claim.</p><p><strong>Methods: </strong>Particle size was determined using a dynamic image analyzer and represented as Feret Max at 10th (FERET Max D [v, 0.1]), 50th (FERET Max D [v, 0.5]), and 90th percentiles (FERET Max D [v, 0.9]). Particle imaging was performed using scanning electron microscopy and a Quorum sputter coater. Lipase activity was measured according to the European Pharmacopoeia (Ph. Eur) and International Pharmaceutical Federation (FIP) procedures. The measured activity was compared against the label claims to identify the percentage of deviations. Lipase release at different pH (release kinetics) was also determined subsequently.</p><p><strong>Results: </strong>The particle size of the PERT preparations differed considerably. There were deviations in the actual lipase content from the label claim, ranging from 85.8% (Gastrozym 10000) to 177.5% (Pancreolan 6000). Under the simulated conditions, most PERT preparations released the enzyme lipase at an acidic pH present in the stomach before reaching the duodenum.</p><p><strong>Conclusion: </strong>PERT preparations available in Europe and Canada exhibit significant differences in terms of physical and enzyme release kinetics. Careful evaluation is needed when interchanging these preparations, as it could impact the therapeutic outcomes.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144498969","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":"Demonstrating Bioequivalence for a Lumacaftor Monosubstance Formulation Versus Orkambi^® (Lumacaftor/Ivacaftor) in Healthy Subjects.","authors":"Alexandra Papaelias, Darcy Lidington, Steffen-Sebastian Bolz","doi":"10.1007/s40268-025-00514-9","DOIUrl":"https://doi.org/10.1007/s40268-025-00514-9","url":null,"abstract":"<p><strong>Background and objective: </strong>Lumacaftor is an active ingredient in the US Food and Drug Administration-approved combination medication Orkambi^®, which is used for treating cystic fibrosis. Experimental evidence suggests that lumacaftor can be used as a monotherapy to improve brain perfusion and memory in heart failure. To clinically assess this therapeutic intervention, a formulation with demonstrated bioequivalence to the currently approved combination product is required.</p><p><strong>Methods: </strong>This comparative bioavailability and food-effect study compared lumacaftor pharmacokinetics in healthy patients following: (i) oral administration of lumacaftor (400 mg; Test Product) or Orkambi^® (lumacaftor 400 mg/ivacaftor 250 mg; Reference Product) in the fed state and (ii) oral administration of lumacaftor (400 mg; Test Product) in the fasted to fed state. Plasma lumacaftor concentrations were measured with a standard liquid chromatography with tandem mass spectrometry approach.</p><p><strong>Results: </strong>The \"Test-to-Reference ratio\" of the geometric least-square means for maximum plasma concentration and area under the curve met the Food and Drug Administration-defined criteria for bioequivalence; median times to maximum plasma concentration values were not statistically different. The \"Fed to Fasted ratio\" of the geometric least-square means for maximum plasma concentration and area under the curve indicated a clear food effect on bioavailability. Lumacaftor exposure was approximately two times higher when administered with fatty foods than when taken in a fasting state. The monosubstance formulation was well tolerated.</p><p><strong>Conclusions: </strong>We conclude that the lumacaftor monosubstance formulation delivers lumacaftor exposure that is not meaningfully different than the currently approved combination product.</p><p><strong>Clinical trial registration: </strong>ClinicalTrials.gov identifier: NCT05968612.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144477586","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":"Pharmacokinetic Comparison of Novel Tablet-in-Tablet and Conventional Ketorolac Tromethamine Tablets in Beagle Dogs.","authors":"Xiang-Yang Xie, Yuan Zeng, Zhi-Long Chen, Yu-Liang Li, Wen Lin, Hui Liu, Yi-Hui Ma, Guo-Wei Zhang","doi":"10.1007/s40268-025-00516-7","DOIUrl":"10.1007/s40268-025-00516-7","url":null,"abstract":"<p><strong>Background and objective: </strong>Ketorolac tromethamine (KT), a nonsteroidal anti-inflammatory drug (NSAID) and cyclooxygenase inhibitor, is commonly used for the management of moderate to severe pain. The objective of this study was to compare the pharmacokinetic characteristics of KT in beagle dogs following oral administration of conventional tablets and a novel tablet-in-tablet (TIT) formulation.</p><p><strong>Methods: </strong>A comparative dissolution study was conducted to evaluate the release profiles of both formulations. Non-compartmental analysis was used to determine the pharmacokinetic parameters of each formulation.</p><p><strong>Results: </strong>Approximately 20% of the administered KT from the TIT formulation was released within the first 30 min, with a cumulative release exceeding 90% at 16 h. In contrast, the conventional tablets released about 50% of the drug within 30 min and completed the release at 4 h. In the single-dose study, the time to reach maximum plasma concentration (T_max) for conventional tablets was 1 h, while T_max for the TIT formulation was 5 h. Both maximum concentration (C_max) and area under the concentration-time curve (AUC) for the TIT formulation were lower than those for conventional tablets. In the repeated-dose study, when equivalent doses (35 mg) of conventional tablets were administered in divided daily doses, the TIT formulation showed no significant differences in most steady-state pharmacokinetic parameters, except for T_max,ss.</p><p><strong>Conclusion: </strong>The results of this study suggest that the development of a novel KT tablet formulation utilizing the push-pull osmotic pump (PPOP) and tablet-in-tablet techniques warrants further investigation in clinical trials.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144340550","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":"Systematic Review and Meta-analysis of the Clinical Efficacy of Octreotide in Combination with Ulinastatin in the Treatment of Acute Pancreatitis.","authors":"Long-Xun Zhu, Yong Chen, Xiang-Fan Chen, Nan Sheng, Pan-Feng Feng","doi":"10.1007/s40268-025-00518-5","DOIUrl":"10.1007/s40268-025-00518-5","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objectives: &lt;/strong&gt;Acute pancreatitis (AP) is a serious disease characterized by local inflammatory responses in the pancreas. The annual incidence rate of acute pancreatitis is 4.9-73.4 per 100,000 people. Among these, approximately 20% develop into moderately severe acute pancreatitis (MSAP) or severe acute pancreatitis (SAP), with a mortality rate of 13-35%. The aim of this study is to evaluate the efficacy and safety of octreotide in combination with ulinastatin in the treatment of acute pancreatitis using meta-analysis.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;Chinese and English databases, including China National Knowledge Infrastructure Database (CNKI), WanFang database (WANFANG), Chinese Scientific Journals Full-text Database (VIP database), PubMed, Medline, and Web of Science, were searched for randomized controlled trials (RCTs) about octreotide in combination with ulinastatin in the treatment of acute pancreatitis from January 2019 to April 2024. Retrieved literature was screened independently by two researchers, and the methodological quality of included publications was evaluated according to bias risk assessment tool recommended by Cochrane 5.1. Data were statistically analyzed by using RevMan5.3 software.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;A total of 3026 patients from 30 studies in accordance with the criteria were included, including experimental group (n = 1516) and control group (n = 1510). Meta-analysis results showed that octreotide combined with ulinastatin could increase the effective rate of treatment for acute pancreatitis (relative risk (RR) = 1.23, 95% CI 1.19-1.27, P &lt; 0.00001). The time in the experimental group for hospitalization (standardized mean difference (SMD) = -2.00, 95% CI [-2.67, -1.34], P &lt; 0.00001), disappearance of abdominal pain (SMD = -1.75, 95% CI [-2.21, -1.29], P &lt; 0.00001), disappearance of nausea and vomiting (SMD = -2.03, 95% CI [-2.93, -1.13], P &lt; 0.00001), disappearance of abdominal distension (SMD = -2.02, 95% CI [-2.59, -1.44], P &lt; 0.00001), and disappearance of peritoneal irritation (SMD = -2.20, 95%CI [-3.95, -0.46], P &lt; 0.00001) was shorter than in the control group. The levels in the experimental group of TNFα (SMD = -2.01, 95% CI [-2.71, -1.32], P &lt; 0.00001), CRP (SMD = -2.50, 95% CI [-3.20, -1.79], P &lt; 0.00001), IL-6 (SMD = -2.67, 95% CI [-3.48, -1.85], P &lt; 0.00001), IL-8 (SMD = -2.92, 95% CI [-4.02, -1.83], P &lt; 0.00001), serum amylase concentration (SMD = -2.83, 95% CI [-4.07, -1.60], P &lt; 0.00001), and urine amylase concentration (SMD = -2.34, 95% CI [-3.81, -0.88], P &lt; 0.00001) were lower compared with control group. There was no statistically significant difference in the incidence of adverse reactions between the experimental and control groups.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The combination of octreotide and ulinastatin can improve the intestinal mucosal barrier function, reduce inflammatory response, and decrease amylase levels in patients with acute pancreat","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":""},"PeriodicalIF":2.2,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144334258","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":"Safety Evaluation of Contezolid (MRX-I) Versus Linezolid in Sprague-Dawley Rats.","authors":"Liping Wei, Min Hong, Min Lu, Yimin Qian, Qingmei Li, Naping Tang, Hua Li, Yan Chang, Yunliang Qiu","doi":"10.1007/s40268-025-00504-x","DOIUrl":"10.1007/s40268-025-00504-x","url":null,"abstract":"<p><strong>Background & objectives: </strong>Contezolid (MRX-I) is a novel ortho-fluorophenyl dihydropyridone developed by MicuRx Pharmaceuticals, Inc. It has been approved for the treatment of drug-resistant Gram-positive bacterial infections with relatively lower toxicity than other oxazolidinones such as linezolid. However, the toxicity profile has not yet been completely revealed. The aim of this study was to disclose the toxicity of contezolid in Sprague-Dawley (SD) rats and compare its toxicity profile with linezolid in a standard 4-week toxicity study.</p><p><strong>Methods: </strong>In this study, SD rats were orally administered with contezolid at doses of 20, 100, or 200/300 mg/kg/day for 28 consecutive days followed by a 28-day recovery period. Linezolid at doses of 100 or 200 mg/kg/day served as a comparator. Clinical observations, body weight, food consumption, hematology, clinical chemistry, urinalysis, and histopathological examinations were conducted.</p><p><strong>Results: </strong>All females in the 200 mg/kg/day linezolid group were subjected to unscheduled death due to myelosuppression within the first 2 weeks. No abnormalities were noted in the 200 mg/kg/day contezolid group, and the dose level was escalated to 300 mg/kg/day from day 15. Myelosuppression or myelosuppression-associated effects were comparable between the 300-mg/kg/day contezolid group and the 100-mg/kg/day linezolid group. The 'no observed adverse effect level' (NOAEL) of contezolid was determined to be 100 mg/kg/day (with an average AUC_0-24 h of 268.4 μg*h/mL). At the same dose levels, the toxicity of contezolid was significantly lower than that of linezolid.</p><p><strong>Conclusion: </strong>These findings demonstrate that contezolid exhibits a favorable safety profile compared with linezolid in this 4-week repeated-dose toxicity study in rats.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"127-140"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185790/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992192","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":"Patient-Reported Outcome Measures in Patients with Rheumatoid Arthritis, Psoriasis, or Psoriatic Arthritis Treated with GP2015, an Etanercept Biosimilar: Results from Two Phase III Studies (EGALITY and EQUIRA).","authors":"Diamant Thaçi, Sascha Gerdes, Hendrik Schulze-Koops, Yannick Allanore, Arthur Kavanaugh, Charlotte Both, Sreekanth Gattu, Sohaib Hachaichi, Marco Matucci-Cerinic","doi":"10.1007/s40268-025-00507-8","DOIUrl":"10.1007/s40268-025-00507-8","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background and objective: &lt;/strong&gt;GP2015 is an etanercept biosimilar. Equivalent efficacy and comparable safety of GP2015 to reference etanercept (ref-ETN) was demonstrated in two phase III studies, one in patients with moderate-to-severe chronic plaque-type psoriasis (PsO; EGALITY study) and the other in patients with rheumatoid arthritis (RA; EQUIRA study). EGALITY also included patients with reported psoriatic arthritis (PsA). Here, patient-reported outcome (PRO) data from both studies are presented.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;EGALITY included 531 patients with PsO and EQUIRA included 376 patients with RA. In EGALITY, patients who had achieved ≥ 50% improvement in Psoriasis Area and Severity Index (PASI) at week 12 either continued the initial treatment or underwent three treatment switches between GP2015 and ref-ETN starting at week 12. In EQUIRA, patients with at least moderate European League Against Rheumatism response at week 24 received GP2015 up to week 48. Assessed PROs included Dermatology Life Quality Index (DLQI) and EuroQol five-dimension health status questionnaire (EQ-5D-5L) in EGALITY, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score in EQUIRA, and Health Assessment Questionnaire-Disability Index (HAQ-DI) in both studies.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;In EGALITY, mean DLQI decreased from baseline in the GP2015 and ref-ETN groups, and the mean (standard deviation [SD]) percent reductions from baseline in DLQI were comparable between groups at week 12 (GP2015, - 67.7 [40.7]; ref-ETN, - 67.3 [30.6]), and were sustained after the switch at week 52 ('continued GP2015,' - 77.3 [36.5]; 'continued ref-ETN,' - 72.8 [33.7]; 'switched GP2015,' - 73.9 [37.0]; 'switched ref-ETN,' - 78.1 [30.9]). The proportion of patients with EQ-5D-5L scores of 1 ('no problems') improved from baseline to week 52 for all five dimensions and was comparable between treatment groups. In EGALITY, in patients with reported PsA at baseline, mean (SD) HAQ-DI scores decreased from baseline, and scores were comparable between treatment groups at week 12 (GP2015, 0.6 [0.7]; ref-ETN, 0.6 [0.6]) and after switching at week 52 ('continued GP2015,' - 0.4 [0.6]; 'continued ref-ETN,' - 0.4 [0.6]; 'switched GP2015,' - 0.4 [0.6]; 'switched ref-ETN,' - 0.1 [0.4]). In EQUIRA, the proportion of patients achieving HAQ-DI in normal range (≤ 0.5) was comparable between treatment groups up to week 48 ('continued GP2015,' 36.7%; 'switched to GP2015,' 39.9%). The mean FACIT-Fatigue scores increased from baseline and the mean (SD) percent change from baseline in FACIT-Fatigue score at week 24 was 9.6 (9.5) in the 'continued GP2015' and 11.4 (9.7) in the 'switched to GP2015' groups; the scores were sustained after switching until week 48.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusion: &lt;/strong&gt;Treatment with GP2015 and ref-ETN resulted in similar improvements in PROs and quality-of-life scores across the three diseases, namely RA, PsA, and PsO. These improvements wer","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"107-115"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185822/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144056591","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":"Evaluation of Anti-SARS-CoV-2 IgG Responses in a Clinical Study of a Biosimilar Candidate to Denosumab Using Singlicate Analysis.","authors":"Sandra Ribes, Natalia Krivtsova, Celine Schelcher, Ana Villalba-Izquierdo, Falko Reiss, Mandy Richter, Katrin Reisinger, Johann Poetzl","doi":"10.1007/s40268-025-00510-z","DOIUrl":"10.1007/s40268-025-00510-z","url":null,"abstract":"<p><strong>Background and objectives: </strong>During the coronavirus disease-2019 (COVID-19) pandemic there was the uncertainty that the long-term immune response generated upon natural infection or triggered by available severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) vaccines could impact the clinical endpoints of ongoing clinical trials, in particular, whether the immunogenicity of biotherapeutics could be affected.</p><p><strong>Methods: </strong>Here, we describe the different stages to build an adequate COVID-19 serology testing strategy to ultimately assess whether the presence of anti-SARS-CoV-2 antibodies could impact the immunogenicity data of a clinical trial supporting the approval of GP2411 (Jubbonti^®/Wyost^®; a denosumab biosimilar to Prolia/XGeva) conducted during the pandemic. We first assessed the sensitivity and specificity of US Food and Drug Administration Emergency Use Authorization (FDA EUA)-approved commercial SARS-CoV-2 anti-IgG enzyme-linked immunosorbent (ELISA) assay. Then, we validated the assay in accordance with bioanalytical guidelines and demonstrated that the analysis of validation parameters as singlicates met all bioanalytical acceptance criteria and showed comparable results to those of duplicate analyses. Lastly, we report data on anti-SARS-CoV-2 IgG antibody responses in healthy participants treated with a single dose of a biotherapeutic.</p><p><strong>Results: </strong>SARS-CoV-2 serology was assessed in 1970 serum samples collected from 499 healthy participants who were dosed throughout a clinical study that was conducted during the COVID-19 pandemic. Anti-SARS-CoV-2 IgG antibodies triggered by natural infection and/or vaccination were detected in 1165 serum samples from 82% of the study participants. Anti-SARS-COV-2 IgG responses were of comparable magnitude in study participants who were vaccinated during the course of the study or had a confirmed COVID-19 infection. A total of 6408 serum samples from the same study were evaluated for the presence of anti-drug antibodies (ADAs), with 64% of the participants being positive. Independent of the presence of anti-SARS-CoV-2 IgG antibodies, all ADA-positive study participants showed ADAs of very low magnitude. Neutralizing ADAs were detected in less than 1% of study participants without an association to anti-SARS-CoV-2 IgG responses.</p><p><strong>Conclusions: </strong>The established bioanalytical strategy allowed the reliable detection of COVID-19 adaptive responses in study participants. The development of anti-SARS-CoV-2 IgG responses (triggered by either a natural infection or a vaccine) did not have any clinically meaningful impact on the immunogenicity of the biotherapeutic administered in the study.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"141-152"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185828/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144129410","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":"Network Meta-Analysis of Pharmacological Therapies for Long-Term Prophylactic Treatment of Patients with Hereditary Angioedema.","authors":"Sarah Walsh, Meaghan Bartlett, Elizabeth M Salvo-Halloran, John Sears, Yinglei Li, Maebh Kelly, Simona Gavata-Steiger, Chiara Nenci, Iris Jacobs, Ingo Pragst, Neelanjana Ray, Imtiaz A Samjoo","doi":"10.1007/s40268-025-00511-y","DOIUrl":"10.1007/s40268-025-00511-y","url":null,"abstract":"<p><strong>Background and objectives: </strong>Several treatments for long-term prophylaxis (LTP) of hereditary angioedema (HAE) are in clinical use, such as garadacimab, lanadelumab, subcutaneous C1 esterase inhibitor (C1INH), and berotralstat. In the absence of head-to-head comparative evidence, indirect comparison methods are needed to compare LTP treatments in patients with HAE. The objective of this analysis was to estimate the comparative efficacy, safety, and impact on quality of life of LTP treatments for patients with HAE through NMAs.</p><p><strong>Methods: </strong>A systematic literature review was conducted to identify randomized controlled trials (RCTs) investigating LTP treatments in patients (at least 12 years old) with HAE (PROSPERO protocol #CRD42022359207). A network meta-analysis (NMA) feasibility assessment evaluated trial suitability and Bayesian NMAs were conducted for evaluable efficacy, safety, and quality of life (QoL) outcomes.</p><p><strong>Results: </strong>The results of these NMAs show improved efficacy, QoL, and reduced rate of adverse events with garadacimab (200 mg once monthly), lanadelumab (300 mg every two or four weeks), subcutaneous C1INH (60 IU/kg twice weekly), and berotralstat (150 mg once daily) compared to placebo in the treatment of patients with HAE. For the primary outcome of time-normalized number of HAE attacks, garadacimab statistically significantly reduced the rate of attacks compared to lanadelumab Q4W and berotralstat. A similar statistically significant reduction was shown for HAE attacks treated with on-demand treatment. Garadacimab showed statistically significant reduction in the rate of moderate and/or severe HAE attacks compared to lanadelumab Q2W. Garadacimab also showed statistical improvements in change from baseline in AE-QoL total score as compared to berotralstat.</p><p><strong>Conclusions: </strong>Overall, garadacimab ranked as the most probable effective treatment among all comparators assessed, with lanadelumab Q2W or subcutaneous C1INH ranking second, across most outcomes.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"161-178"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163333","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":"Opinion of the Italian Association of Myology on Ataluren for the Treatment of Nonsense Mutation Duchenne Muscular Dystrophy.","authors":"Luca Bello, Pietro Riguzzi, Emilio Albamonte, Guja Astrea, Roberta Battini, Andrea Barp, Angela L Berardinelli, Enrico S Bertini, Noemi Brolatti, Claudio Bruno, Stefania Corti, Adele D'Amico, Maria Grazia D'Angelo, Gianfranco Dallavalle, Rocco Liguori, Lorenzo Maggi, Francesca Magri, Michelangelo Mancuso, Riccardo Masson, Eugenio Mercuri, Carlo Minetti, Sonia Messina, Tiziana Mongini, Olimpia Musumeci, Vincenzo Nigro, Marika Pane, Chiara Panicucci, Marina Pedemonte, Antonella Pini, Luisa Politano, Stefano Previtali, Federica Ricci, Giulia Ricci, Lucia Ruggiero, Valeria Sansone, Gabriele Siciliano, Antonio Trabacca, Federica Trucco, Daniele Velardo, Elena Pegoraro, Giacomo P Comi","doi":"10.1007/s40268-025-00512-x","DOIUrl":"10.1007/s40268-025-00512-x","url":null,"abstract":"<p><p>The Italian Duchenne muscular dystrophy expert clinicians, gathered in the Italian Association of Myology (AIM), intend to express a position against the suspension of the Marketing Authorization of ataluren (Translarna^®) for the treatment of nonsense mutation Duchenne muscular dystrophy. The marketing authorization has been recently withdrawn by the European Commission following a recommendation from the Committee for Medicinal Products for Human Use of the European Medicines Agency. This negative recommendation was based on the fact that three randomized controlled trials of ataluren in nonsense mutation Duchenne muscular dystrophy (007, 020, and 041) have failed to show statistically significant differencs in favor of the treatment in the selected primary outcomes for each individual study, i.e., 6-min walk distance, in the intent-to-treat population for 007 and 020 and in a subgroup for 041. However, observed differences always favored treatment, and several clinically meaningful secondary outcomes were positive and statistically significant across studies. Importantly, the largest and longest phase III study (041) showed a statistically significant effect in favor of ataluren in the wider intent-to-treat population. Furthermore, a long-term registry of \"real-world\" ataluren treatment data (Strategic Targeting of Registries and Database of Excellence, STRIDE), in addition to confirming a reassuring safety profile, suggested a prolonged maintenance of ambulatory, upper limb, and respiratory function. We deem that a withdrawal of ataluren from the European market would harm not only patients with nonsense mutation Duchenne muscular dystrophy, but the whole neuromuscular field, in which clinical trials are challenging because of the heterogenous complex slow-progressing nature of the disorders.</p>","PeriodicalId":49258,"journal":{"name":"Drugs in Research & Development","volume":" ","pages":"99-106"},"PeriodicalIF":2.2,"publicationDate":"2025-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12185855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144163374","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}