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Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents.
- Source :
-
The New England journal of medicine [N Engl J Med] 2018 Sep 06; Vol. 379 (10), pp. 913-923. - Publication Year :
- 2018
-
Abstract
- Background: Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains resistant to current antiviral agents.<br />Methods: We conducted two randomized, double-blind, controlled trials involving otherwise healthy outpatients with acute uncomplicated influenza. After a dose-ranging (10 to 40 mg) placebo-controlled trial, we undertook a placebo- and oseltamivir-controlled trial of single, weight-based doses of baloxavir (40 or 80 mg) in patients 12 to 64 years of age during the 2016-2017 season. The dose of oseltamivir was 75 mg twice daily for 5 days. The primary efficacy end point was the time to alleviation of influenza symptoms in the intention-to-treat infected population.<br />Results: In the phase 2 trial, the median time to alleviation of influenza symptoms was 23.4 to 28.2 hours shorter in the baloxavir groups than in the placebo group (P<0.05). In the phase 3 trial, the intention-to-treat infected population included 1064 patients; 84.8 to 88.1% of patients in each group had influenza A(H3N2) infection. The median time to alleviation of symptoms was 53.7 hours (95% confidence interval [CI], 49.5 to 58.5) with baloxavir, as compared with 80.2 hours (95% CI, 72.6 to 87.1) with placebo (P<0.001). The time to alleviation of symptoms was similar with baloxavir and oseltamivir. Baloxavir was associated with greater reductions in viral load 1 day after initiation of the regimen than placebo or oseltamivir. Adverse events were reported in 20.7% of baloxavir recipients, 24.6% of placebo recipients, and 24.8% of oseltamivir recipients. The emergence of polymerase acidic protein variants with I38T/M/F substitutions conferring reduced susceptibility to baloxavir occurred in 2.2% and 9.7% of baloxavir recipients in the phase 2 trial and phase 3 trial, respectively.<br />Conclusions: Single-dose baloxavir was without evident safety concerns, was superior to placebo in alleviating influenza symptoms, and was superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza. Evidence for the development of decreased susceptibility to baloxavir after treatment was also observed. (Funded by Shionogi; JapicCTI number, 153090, and CAPSTONE-1 ClinicalTrials.gov number, NCT02954354 .).
- Subjects :
- Adolescent
Adult
Antiviral Agents adverse effects
Antiviral Agents therapeutic use
Child
Dibenzothiepins
Double-Blind Method
Endonucleases antagonists & inhibitors
Female
Humans
Influenza, Human virology
Intention to Treat Analysis
Kaplan-Meier Estimate
Male
Middle Aged
Morpholines
Oxazines adverse effects
Pyridines adverse effects
Pyridones
Thiepins adverse effects
Triazines adverse effects
Viral Load
Virus Replication drug effects
Young Adult
Antiviral Agents administration & dosage
Influenza, Human drug therapy
Oseltamivir therapeutic use
Oxazines administration & dosage
Pyridines administration & dosage
Thiepins administration & dosage
Triazines administration & dosage
Subjects
Details
- Language :
- English
- ISSN :
- 1533-4406
- Volume :
- 379
- Issue :
- 10
- Database :
- MEDLINE
- Journal :
- The New England journal of medicine
- Publication Type :
- Academic Journal
- Accession number :
- 30184455
- Full Text :
- https://doi.org/10.1056/NEJMoa1716197