Baloxavir Marboxil Tablets (Xofluza)
November 30, 2018
By William Elliott, MD, FACP, and James Chan, PharmD, PhD
Dr. Elliott is Assistant Clinical Professor of Medicine, University of California, San Francisco.
Dr. Chan is Associate Clinical Professor, School of Pharmacy, University of California, San Francisco.
Drs. Elliott and Chan report no financial relationships relevant to this field of study.
For the first time in nearly 20 years, the FDA has approved a new antiviral drug for the treatment of influenza. Baloxavir marboxil is a prodrug for baloxavir, which is the first in the class of polymerase acidic endonuclease inhibitors. It differs from oseltamivir, which is an influenza neuraminidase inhibitor. Baloxavir received a priority review and is distributed as Xofluza.
Indications
Baloxavir is indicated for the treatment of acute uncomplicated influenza in patients ≥ 12 years of age who have shown symptoms for no more than 48 hours.1 Prescribers should consider currently available surveillance information on influenza virus drug susceptibility patterns and treatment effects before prescribing baloxavir.1
Dosage
The dose is a single tablet taken orally within 48 hours of symptom onset.1 The dose is 40 mg for patients who weigh between 40 kg and 80 kg. For those patients ≥ 80 kg, the dose is 80 mg. The tablets may be taken without regard to meals. Coadministration with food or drugs containing polyvalent cations (e.g., dairy products, calcium-fortified beverages, antacids) should be avoided.
Potential Advantages
Baloxavir results in more rapid decline in infectious viral load than oseltamivir and shorter median duration of infectious virus detection (24 hours vs. 72 hours).2 Because of its long elimination half-life (average, 79 hours), baloxavir can be given as a single dose compared to a twice-daily dose for five days for oseltamivir. Cross-resistance is not expected because of the different target sites for polymerase acidic endonucluease inhibitors and neuraminidase inhibitors.1
Potential Disadvantages
The effectiveness of baloxavir was established mainly in Asian subjects (83%), as the drug was developed in Japan.1,2 Based on population pharmacokinetics, baloxavir exposure was approximately 35% lower in non-Asians, although this is not considered to be clinically significant.1 Effectiveness in patients at high risk of influenza complications (age > 65 years, comorbidities) has not been reported. Based on limited data, baloxavir may be less effective against influenza B.1 Polyvalent-containing foods and drugs significantly decrease the absorption of baloxavir.1
Comments
The efficacy and safety of baloxavir was evaluated in two randomized, double-blind studies during two different influenza seasons in otherwise healthy subjects with uncomplicated influenza.1,2 In trial 1 (n = 400 Asians), subjects were randomized to a single-dose of baloxavir (10 mg, 20 mg, or 40 mg) or placebo. In trial 2 (n = 1,436; 78% Asians), subjects were randomized to baloxavir 40 mg (body weight < 80 kg) or 80 kg (body weight ≥ 80 kg), oseltamivir (75 mg twice daily × five days), or matching placebo. The primary endpoint was time to alleviation of symptoms (start of regimen until all seven symptoms were rated as absent or mild for at least 21.5 hours). The seven symptoms included cough, sore throat, headache, nasal congestion, feverishness or chills, muscle or joint pain, and fatigue. These were assessed on a four-point scale. Virologic endpoints included infectious virus and viral RNA titers.2 Virus type mainly was influenza A/H1N1 (63% in trial 1) and A/H3N2 (90% in trial 2).
Overall median times to alleviation of symptoms were 50 hours for baloxavir (40 mg) vs. 78 hours for placebo in trial 1 and 54 hours vs. 80 hours, respectively, in trial 2. Benefit was evident by day 2. There was greater benefit if treatment was initiated within 24 hours of onset of symptoms.2 The median time to fever resolution was shorter with baloxavir compared to placebo (24.5 hours vs. 42 hours). Baloxavir was associated with a more rapid decline in infectious viral load compared to placebo or oseltamivir.2 However, the median times to alleviation of symptoms were similar between baloxavir and oseltamivir (53.5 hours vs. 53.8 hours). The median time to return to usual health was shorter with baloxavir compared to oseltamivir but did not reach statistical significance (129 hours vs. 160 hours; P = 0.06).
Approximately 10% of those treated with baloxavir developed viral mutation, mainly with viral type A(H3N2), leading to resistant variants.2 Adverse events deemed related to treatment regimens were more common with oseltamivir (8.4% vs. 4.4%).2 There was no difference in the frequency of complications that resulted in antibiotic use (3.5% with baloxavir, 4.3% with placebo, and 2.4% with oseltamivir).2
Clinical Implications
Baloxavir provides a single-dose treatment that is at least as effective as oseltamivir for five days. The CDC recommends prompt use (within 48 hours of illness onset) of antivirals, particularly in patients at high risk of developing flu-related complications.3,4 The authors of a recently completed clinical trial compared baloxavir, placebo, and oseltamivir in subjects at high risk of influenza complications, but the results have not been reported yet.5 The drug’s wholesale acquisition cost has been set at $150 compared to $87 for a five-day course for generic oseltamivir.
REFERENCES
- Genentech. Xofluza (baloxavir marboxil) full prescribing information. Available to view online at: https://bit.ly/2PbbLWF. Accessed Nov. 5, 2018.
- Hayden FG, Sugaya N, Hirotsu N, et al. Baloxavir marboxil for uncomplicated influenza in adults and adolescents. N Engl J Med 2018;379:913-923.
- Centers for Disease Control and Prevention. Prompt use of antivirals is key this flu season. Available at: https://bit.ly/2SNy0QY. Accessed Nov. 5, 2018.
- Centers for Disease Control and Prevention. People at high risk of developing serious flu-related complications. Available at: https://bit.ly/2jHFmHE. Accessed Nov. 5, 2018.
- ClinicalTrials.gov. Study of S-033188 (baloxavir marboxil) Compared with placebo or oseltamivir in patients with influenza at high risk of influenza complications (CAPSTONE 2). Available online at: https://bit.ly/2QlDalx. Accessed Nov. 5, 2018.
For the first time in nearly 20 years, the FDA has approved a new antiviral drug for the treatment of influenza.
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