METHODS: This was a Phase 2 study of the oral RSV fusion protein inhibitor AK0529 in infants aged 1-24 months, hospitalized with RSV infection. In Part 1, patients (n = 24) were randomized 2:1 to receive a single dose of AK0529 up to 4 mg/kg or placebo. In Part 2, patients (n = 48) were randomized 2:1 to receive AK0529 at 0.5, 1, or 2 mg/kg bid or placebo for 5 days. Sparse pharmacokinetic samples were assessed using population pharmacokinetics modelling. Safety, tolerability, viral load, and respiratory signs and symptoms were assessed daily during treatment.
RESULTS: No safety or tolerability signals were detected for AK0529: grade ≥3 treatment-emergent adverse events occurring in 4.1% of patients in AK0529 and 4.2% in placebo groups, respectively, and none led to death or withdrawal from the study. In Part 2, targeted drug exposure was reached with 2 mg/kg bid. A numerically greater reduction in median viral load with 2 mg/kg bid AK0529 than with placebo at 96 h was observed. A -4.0 (95% CI: -4.51, -2.03) median reduction in Wang Respiratory Score from baseline to 96 h was observed in the 2 mg/kg group compared with -2.0 (95% CI: -3.42, -1.82) in the placebo group.
CONCLUSIONS: AK0529 was well tolerated in hospitalized RSV-infected infant patients. Treatment with AK0529 2 mg/kg bid was observed to reduce viral load and Wang Respiratory Score.
CLINICAL TRIALS REGISTRATION: NCT02654171.
OBJECTIVE: To estimate the global burden of bone cancer from 1990 to 2023 and forecast future trends to 2050.
DESIGN, SETTING, AND PARTICIPANTS: This systematic analysis estimated bone cancer incidence, mortality, and disability-adjusted life-years (DALYs) in 204 countries and territories grouped by GBD super-regions and World Bank income groups from 1990 to 2023, with forecasts through 2050. Individuals of all ages with bone cancers included in the GBD 2023 study were included in analyses. Data were analyzed from June 2023 to July 2025.
MAIN OUTCOMES AND MEASURES: The GBD 2023 study used standardized estimation methods to describe bone cancer incidence, mortality, and DALYs in 2023, as well as trends over the past 3 decades and forecasts through 2050. All estimates are presented with 95% uncertainty intervals (UIs), and age-standardized rates (ASRs) were calculated using GBD-specific age weights.
RESULTS: In 2023, there were 111 000 (95% UI, 81 300-164 000) malignant bone cancer cases, 76 600 (95% UI, 60 700-96 300) deaths, and 3.02 million (95% UI, 2.29 million-3.96 million) DALYs globally. A bimodal age distribution was noted in both incidence (peaking at ages 10 to 14 years and 65 to 69 years) and mortality (peaking at ages 15 to 19 years and 65 to 69 years). The highest ASRs for incidence were in Southeast Asia, East Asia, and Oceania (1.6 per 100 000; 95% UI, 1.1-2.4), while Sub-Saharan Africa had the highest ASRs for DALYs (51.0 per 100 000; 95% UI, 27.7-79.7). By World Bank income group, upper-middle-income countries had the highest ASRs for incidence, whereas low-income countries exhibited the highest ASRs for both mortality and DALYs. Globally, incident cases, deaths, and DALYs increased from 1990 to 2023, while global mortality and DALY ASRs were relatively stable; high-income countries experienced a decline in mortality and DALY ASRs. Forecasts suggest a potential increase in global cases and deaths by 2050.
CONCLUSIONS AND RELEVANCE: In this systematic analysis, the burden of bone cancer varied by age, geography, and time, underscoring global disparities. These findings provide valuable insights to inform health system planning and resource allocation tailored to different settings.