ICON is an American Irish-headquartered healthcare intelligence and clinical research organisation that provides consulting, clinical development and commercialisation services for the pharmaceutical industry. As of November 2021[update], ICON had 38,000 employees in 147 locations spread across 46 countries.
PURPOSE:Patients with refractory Mycobacterium avium complex lung disease (MACLD) represent a difficult-to-treat population with limited treatment options. In the CONVERT trial in refractory MACLD, amikacin liposome inhalation suspension (ALIS) plus multidrug therapy (MDT) resulted in higher culture conversion (CC) than MDT alone in the first 6 months of treatment (29% vs 9%). Adverse events (AEs) were reported in 98% and 91% of patients in the ALIS plus MDT and MDT alone arms, respectively, mostly of mild to moderate severity. A simultaneous assessment of efficacy and safety could be informative for clinical decision-making. METHODS:A post hoc analysis of CONVERT was performed to compare time spent in a state of CC without severe AEs (CC-no severe AEs) between treatment with ALIS plus MDT and MDT alone. Time from randomization to month 6 per treatment arm was partitioned into 4 health states: (1) days spent with severe (≥grade 3) AEs prior to CC; (2) days spent without CC without severe AEs; (3) days spent with severe AEs after CC; and (4) days spent with CC-no severe AEs. The CC-no severe AEs, represented the only health state that provided both positive efficacy and safety treatment outcomes to patients. Mean differences in health-state durations across treatment arms with P values were calculated. FINDINGS:Patients treated with ALIS plus MDT spent a mean of 24.3 more days in the health state of CC-no severe AEs than MDT alone (P < 0.001) over 6 months. IMPLICATIONS:In this post hoc analysis of CONVERT, patients with refractory MACLD treated with ALIS plus MDT spent more time experiencing positive treatment outcomes compared with patients treated with MDT alone.
Context: Sjögrens syndrome (SS) is an autoimmune disease. Patients with SS experience an impaired quality of life and impose a significant economic burden on healthcare systems. Aims: This systematic literature review aimed to analyze the direct and indirect costs (ICs), as well as healthcare resource utilization (HRU) among patients with SS. Methods: A literature search was conducted in Medline and EMBASE from January 2020 to August 2024. All costs were standardized to USD and adjusted for inflation to December 2025. Results: A total of 973 citations were screened, with 14 studies meeting the inclusion criteria. These studies were conducted across ten different countries with sample sizes ranging from 12 to 32,184 individuals. Included studies report costs which varied across countries and patient subtypes. Among all patients with SS, the annual mean cost ranged from USD 2556 to USD 17,024, while the costs for patients with pSS, ranged from USD 710 to USD 14,363. sSS was associated with higher absolute costs, while pSS showed a steeper increase over time. Disease severity and comorbidities were associated with higher healthcare expenditures. One study reported annual ICs, reporting losses at approximately USD 39,061. HRU was assessed across seven studies, with outpatient visits ranging between 3.37 and 10.1 per patient per year (PPPY) and inpatient stays that varied from 0.17 to 0.59 PPPY, depending on the disease type and severity. The mean length of stay (LOS) among pSS patients ranged from 2.6 to 13.6 days, with higher emergency department (ED) visits among patients with sSS. Conclusion: This systematic review highlights the substantial and variable economic burden of SS. Costs are higher in sSS and in patients with greater disease severity or comorbidities. Evidence of rising healthcare expenditures in some regions, particularly pSS, underscores the need for improved data collection strategies and policies to address such needs and resource planning.
Rondaptivon pegol (BT200) is a PEGylated RNA aptamer that prolongs von Willebrand factor (VWF) and factor VIII half-lives in patients with hemophilia A and von Willebrand disease (VWD) type 2B. Embryo-fetal safety is particularly relevant given the disproportionate disease burden in women with VWD. Data on placental transfer and developmental safety of PEGylated aptamers remain limited. An embryo-fetal development study was conducted in pregnant rabbits. Animals received rondaptivon pegol subcutaneously (0, 1.5, 5, or 15 mg/kg/day) from gestational days (GDs) 7-19. Maternal toxicokinetic samples and pooled fetal plasma concentrations were collected during gestation to quantify transplacental exposure. Rondaptivon pegol was well tolerated, with no maternal toxicity, no effects on implantation, and no treatment-related fetal malformations. Dose-related reductions in mean fetal body weight (<11%) were considered adverse only at the highest dose level. Maternal systemic exposure was supratherapeutic, with mean Cmax ranging from 133 to 807 µg/mL on GD19, far exceeding the human target concentration (∼1.2 µg/mL). Fetal plasma concentrations were <0.25% of maternal levels across all dose groups, confirming minimal placental transfer. The no-observed-adverse-effect level was 5 mg/kg/day. At maternal systemic exposures ranging from 110- to 670-fold above anticipated clinical levels, rondaptivon pegol did not adversely affect implantation, embryonic viability, or fetal development. These findings provide the first quantitative maternal-fetal pharmacokinetic and developmental safety data for a PEGylated aptamer, supporting further clinical evaluation of rondaptivon pegol in women of reproductive age.
