PC3020: Summary of Baloxavir Marboxil Safety and Efficacy Outcomes in Pediatric Patients Aged 5-11 Years: Data from 3 Studies

Background: School-aged children, particularly those aged 5-17 years, have high rates of seasonal influenza (Reed C. PLoS One. 2012) and contribute substantially to virus transmission, including antiviral-resistant viruses, due to their infection susceptibility, prolonged viral shedding, and close contact rates (Rotrosen ET. Pediatr Clin North Am. 2017). Baloxavir marboxil (BXM) is an oral antiviral prodrug approved for patients ≥12 years. BXM safety and efficacy for influenza was demonstrated in the global phase 3 study CAPSTONE-1 (NCT02949011), a placebo- and oseltamivir (OSL)-controlled trial in patients aged ≥12 years (Ison MG. Lancet Infect Dis. 2020). Recent studies demonstrated BXM was well tolerated and effective in children < 12 years (Baker J. PIDJ. 2020; Hirotsu N. CID. 2020; Yokoyama T. PIDJ. 2020). We conducted a post-hoc analysis to describe the safety and efficacy data for BXM in healthy children aged 5-11 years with acute influenza from 3 clinical studies.

Methods: In this post-hoc analysis, data were included from a global study where children received single dose BXM or twice daily OSL (miniSTONE-2, NCT03629184) and 2 Japanese studies where children received single dose BXM (CV40816, JapicCTI-163417; CV40964, JapicCTI-173811). Body weight-dependent dosing in miniSTONE-2 included BXM 40 mg (≥20 kg) or 2 mg/kg ( < 20 kg), for OSL 30 mg (≤15 kg), 45 mg (>15–≤23 kg), 60 mg (>23–≤40 kg), or 75 mg (>40 kg); CV40816 included BXM 40 mg (≥40 kg), 20 mg (20- < 40 kg), 10 mg (10- < 20 kg) or 5 mg (5- < 10 kg); and for CV40964 was 10 mg (10- < 20 kg) or 1 mg/kg ( < 10 kg). Safety outcomes included adverse events (AEs). Efficacy outcomes included time to alleviation of symptoms (TTAS), time to resolution of fever (TTRF), and time to cessation of viral shedding by titer (TTCVS). Data are summarized descriptively for each study

Results: Baseline and clinical characteristics varied between studies (Table 1). The most frequently reported AE following BXM across studies was vomiting. No new safety concerns or serious AEs were reported for BXM from all studies; therefore, the pediatric safety profile is similar to adults and adolescents. For BXM, median (95% CI) TTAS was 69.8 (43.7-94.9), 44.6 (38.4-61.0), and 45.7 (21.7-NE) hours, respectively for miniSTONE-2, CV40816, and CV40964 (Figure 1A). Median (95% CI) TTRF for each study was 41.2 (23.3-51.4), 20.7 (19.2-23.8), and 34.0 (21.7-NE) hours, respectively and TTCVS was 24.1 (23.1-24.6), 24.0 (NE), and 48.0 (24.0-NE) hours, respectively, for BXM (Figure 1B, C). For OSL, median (95% CI) TTAS, TTRF, and TTCVS were 71.1 (51.7-118.2), 51.3 (23.4-56.8), and 75.8 (68.9-95.6) hours, respectively in miniSTONE-2

Conclusion: This post-hoc analysis of safety and efficacy data from the BXM pediatric program demonstrated single dose BXM was well tolerated and effective at alleviating symptoms in children with active influenza aged 5-11 years