Baloxavir Treatment in Adolescents With Acute Influenza: Subgroup Analysis From the CAPSTONE-1 Trial

Abstract

Background Baloxavir marboxil has demonstrated safety and efficacy in treating adult and adolescent outpatients with acute influenza (CAPSTONE-1 trial). Here, we report a subgroup analysis of outcomes in adolescents from the trial. Methods CAPSTONE-1 was a randomized, double-blind, placebo-controlled study. Eligible adolescent outpatients (aged 12-17 years of age) were randomized in a ratio of 2:1 to a single dose of baloxavir 40/80 mg if less than/greater than or equal to 80 kg or placebo. The main outcomes were the time to alleviation of symptoms (TTAS), duration of infectious virus detection, and incidence of adverse events (AEs). Results Among 117 adolescent patients, 90 (77%) comprised the intent-to-treat infected population (63 baloxavir and 27 placebo; 88.9% A(H3N2)). The median TTAS was 38.6 hours shorter (95% confidence interval: −2.6, 68.4) in the baloxavir group compared with placebo (median TTAS, 54.1 hours vs 92.7 hours, P = .0055). The median time to sustained cessation of infectious virus detection was 72.0 hours for baloxavir compared with 120.0 hours for placebo recipients (P < .0001). Treatment-emergent PA/I38X-substituted viruses were detected in 5 of the 51 (9.8%) baloxavir recipients. In the safety population (76 baloxavir and 41 placebo), AEs were less common in baloxavir than placebo recipients (17.1% vs 34.1%; P = .0421). In the baloxavir group, no AEs except for diarrhea were reported in 2 or more patients. Conclusions Baloxavir demonstrated clinical and virologic efficacy in the otherwise healthy adolescents with acute influenza compared with placebo. There were no safety concerns identified. These results were similar to the adult population in CAPSTONE-1 and support baloxavir as a treatment option in adolescents.

Evaluation of the Clinical Effectiveness of Oseltamivir for Influenza Treatment in Children

“…Favipiravir (T-705), an inhibitor of viral RNA polymerase, has been proven to be effective in the treatment of influenza viruses, including NAI-resistant variants, and is also a potential drug for treating Ebola virus disease virus (EVD) and severe acute respiratory syndrome coronavirus type 2 (SARS-cov-2) ( FangHuangLiChengTanLiu, 2020 ; DziedziejkoPawlik, 2021 ). Baloxavir marboxil (baloxavir), a novel influenza cap-dependent inhibitor of endonuclease-selective polymerase acidic protein, has shown clinical efficacy in rapidly reducing the viral load, shortening the duration of fever, and relieving symptoms ( Chong et al, 2021 ; Portsmouth et al, 2021 ). In addition, compared to the ineffectiveness of NAIs, the efficacy of single and combined use of favipiravir was excellent in vivo ( Imai et al, 2017 ; Wang et al, 2020 ).…”

Severe community-acquired pneumonia in the post COVID-19 era

“…It was firstly approved in Japan and in the USA in 2018, and later in 2021 in the EU and UK for uncomplicated influenza treatment in subjects older than 12 years old. Phase 3 RCTs performed in individuals with uncomplicated influenza [28,29] showed a faster symptom recovery along with an accelerated viral clearance with Baloxavir when compared to placebo. However, none of them found significant differences between Baloxavir and Oseltamivir regarding time to symptom improvement; except in the subgroup of high-risk patients for influenza-complications, who showed a faster recovery with Baloxavir.…”

Influenza: clinical aspects, diagnosis, and treatment

“…First approved in Japan in February 2018 and then in the United States in October 2018, it is now widely approved in >70 countries and geographic areas. This comes after a series of trials demonstrating efficacy for acute uncomplicated influenza in adults and adolescents who are healthy [21,22 ▪ ] or at risk of influenza-related complications [23 ▪▪ ], children [24 ▪▪ ] and as postexposure prophylaxis of household contacts [25 ▪▪ ]. Compared to placebo, baloxavir significantly improved time to improvement [23 ▪▪ ] and time to alleviation [21] of influenza symptoms; and faster viral clearance for adults compared with placebo or oseltamvir [21].…”