Baloxavir effective in adolescents and high-risk flu patients
The selective cap-dependent endonuclease inhibitor baloxavir marboxil (hereafter baloxavir) effectively improves influenza symptoms in adolescent patients and those at high risk for influenza complications, according to two subanalyses of the CAPSTONE studies presented at ECCMID 2019.
Being highlighted was a subanalysis of 90 adolescent patients (aged 12–17 years) from 1,064 patients with acute influenza who were otherwise healthy in the phase III, double-blind CAPSTONE-1 study, which randomized patients 2:1 to a single dose of baloxavir (80 mg for patients ≥80 kg, 40 mg if <80 kg) or placebo. [ECCMID 2019, abstract O0817]
In this subgroup of adolescent patients, the time to alleviation of symptoms (TTAS) was significantly shortened by 38.6 hours with baloxavir than with placebo (median, 54.1 vs 92.7 hours; p=0.0055).
Also, infectious virus was not detected after 24 hours in the baloxavir group, while it took 96 hours before the viral load was cleared in the placebo group (p≤0.001).
There were fewer incidences of adverse events (AEs) in the baloxavir group compared with the placebo group (17.1 percent vs 34.1 percent; p=0.0421). None of the AEs in the baloxavir group occurred at a frequency of ≥2 patients in the adolescent population, except for diarrhoea.
“There were no safety concerns identified. These results were similar to the overall intent-to-treat infected population, and supports baloxavir as a promising treatment option in an adolescent patient population,” said the researchers.
Another subanalysis was on the phase III CAPSTONE-2 study, which randomized 484 patients 1:1:1 to receive single-dose baloxavir (dosage as above), oseltamivir 75 mg twice daily for 5 days, or placebo. Unlike CAPSTONE-1, the CAPSTONE-2 study enrolled patients with fever and influenza symptoms ≤48 hours who were at high risk for complications, including those with comorbidities or aged >65 years. Subjects in the current analysis were a subgroup of patients from CAPSTONE-2 who had influenza B virus infection. [ECCMID 2019, abstract P1122]
The baloxavir group required a significantly shorter time for influenza symptoms to improve compared with the placebo group (median TTIIS*, 74.6 vs 100.6 hours; p<0.05). Specifically, the time to resolution of fever (TTRF) was also shorter in the baloxavir group than in the placebo group (median, 35.8 vs 62.9 hours; p<0.05).
Similar results were seen for time to cessation of infectious viral shedding (TCVS), in favour of baloxavir (median, 72.0 vs 96.0 hours; p<0.05).
When compared with oseltamivir, both outcomes of TTIIS (median, 74.6 vs 101.6 hours; p<0.05) and TCVS (median, 72.0 vs 96.0 hours; p<0.05) were also significantly shorter with baloxavir. While TTRF was shorter in the baloxavir group than the oseltamivir group, the difference was not significant.
“Baloxavir demonstrated clinical and virologic efficacy in influenza B infected outpatients at higher risk for complications … [supporting] baloxavir as a treatment option for type B virus infection,” said the researchers.
The favourable outcome in clinical and virologic activity in turn led to significantly reduced percentage of baloxavir-treated patients who had prespecified complications compared with the placebo group (3.0 percent vs 11.3 percent; p=0.005). The proportion of patients requiring antibacterial therapy (3.6 percent vs 7.7 percent; p=0.155) was also lower with baloxavir vs placebo, although the difference between group was not significant.
The proportion of patients with complications (3.0 percent vs 4.7 percent; p=0.559) or requiring antibacterial therapy (3.6 percent vs 4.7 percent; p=0.778) was comparable between the baloxavir and the oseltamivir groups.