Abstract
Background:
miniSTONE-2 (NCT03629184) was a global, phase 3, randomized, controlled study that investigated the safety and efficacy of single-dose baloxavir marboxil in otherwise healthy children 1–<12 years of age and showed a positive risk-benefit profile. This post hoc analysis evaluated the safety and efficacy of baloxavir versus oseltamivir in children 5–11 years old with influenza.
Methods:
Children received single-dose baloxavir or twice-daily oseltamivir for 5 days. Safety was the primary objective. Efficacy and virological outcomes included time to alleviation of symptoms, duration of fever and time to cessation of viral shedding by titer. Data were summarized descriptively.
Results:
Ninety-four children 5–11 years old were included (61 baloxavir and 33 oseltamivir). Baseline characteristics were similar between the groups. The incidence of adverse events was balanced and low in both treatment groups, with the most common being vomiting (baloxavir 5% vs. oseltamivir 18%), diarrhea (5% vs. 0%) and otitis media (0% vs. 5%). No serious adverse events or deaths occurred. Median (95% CI) time to alleviation of symptoms with baloxavir was 138.4 hours (116.7–163.4) versus 126.1 hours (95.9–165.7) for oseltamivir; duration of fever was comparable between groups [41.2 hours (23.5–51.4) vs. 51.3 hours (30.7–56.8), respectively]. Median time to cessation of viral shedding was shorter in the baloxavir group versus oseltamivir (1 vs. ≈3 days).
Conclusions:
Safety, efficacy and virological results in children 5–11 years were similar to those from the overall study population 1–<12 years of age. Single-dose baloxavir provides an additional treatment option for pediatric patients 5–11 years old with influenza.
Keywords: baloxavir marboxil, influenza, pediatrics, clinical trial
Influenza infection can occur across all pediatric age groups from birth to 18 years.1,2 Although the condition is usually self-limiting in healthy adults, it can be associated with substantial morbidity in children, the elderly and the immunocompromised.3 In children, the severity of influenza and the incidence of complications are inversely associated with age depending on immunologic immaturity, presence of comorbidities and lack of specific cell-mediated immunity4,5; incidence of complications varies by season and may depend on viral subtype, vaccination status and vaccine efficacy.5–7 School-age children have high rates of seasonal influenza8,9 and contribute substantially to virus transmission due to their relative serosusceptibility, prolonged viral shedding and close contact rates.7,10,11
Recommended influenza treatments from the Centers for Disease Control and Prevention include oral oseltamivir, inhaled zanamivir, intravenous peramivir or oral baloxavir marboxil (baloxavir); however, there are limitations such as age restrictions and/or convenience of dosing.12 Baloxavir is a single-dose, oral antiviral approved for the treatment of influenza in otherwise healthy patients (patients with no underlying conditions) ≥5 years old and high-risk patients ≥12 years old. The safety and efficacy of baloxavir for influenza were based on a phase 2 and three phase 3 trials: CAPSTONE-1 (NCT02954354), CAPSTONE-2 (NCT02949011) and miniSTONE-2 (NCT03629184).13–15 Baloxavir is also approved for postexposure prophylaxis in patients ≥5 years old based on the phase 3 BLOCKSTONE (JapicCTI-184180) trial.16 Baloxavir is not approved for patients <5 years of age.
CAPSTONE-1 was a phase 3, randomized, double-blind study of baloxavir versus placebo or oseltamivir in otherwise healthy adults and adolescents ≥12 years of age with influenza.15 CAPSTONE-2 evaluated baloxavir versus placebo or oseltamivir for the treatment of influenza in adults and adolescents ≥12 years of age at high risk of influenza-related complications, such as patients with asthma, chronic lung disease, cardiovascular diseases, compromised immune system, obesity or those who are ≥65 years old.13 In both studies, single-dose baloxavir was well tolerated [adverse events (AEs): CAPSTONE-1: 21% baloxavir and 25% oseltamivir; CAPSTONE-2: 25% vs. 28%]. Baloxavir had superior virological efficacy to oseltamivir and placebo [time to cessation of viral shedding (TCVS) in CAPSTONE-1: 24 hours baloxavir, 72 hours oseltamivir, 96 hours placebo; CAPSTONE-2: 48, 96 and 96 hours, respectively]. Baloxavir was also superior to placebo and comparable with oseltamivir in alleviating symptoms [time to alleviation of symptoms (TTAS) in CAPSTONE-1: 53.7 hours baloxavir, 53.8 hours oseltamivir and 80.2 hours placebo; CAPSTONE-2: 77.0, 85.6 and 102.8 hours, respectively] and in CAPSTONE-2, similar results were observed for time to improvement of influenza symptoms (73 hours baloxavir, 81 hours oseltamivir and 102 hours placebo). BLOCKSTONE showed that single-dose baloxavir markedly reduced the risk of developing influenza in prophylaxed household contacts by 86% versus placebo and was well tolerated.16
Studies have also found that baloxavir was well tolerated and effective in children <12 years of age.14,17,18 miniSTONE-2 was the first global, phase 3, randomized, controlled study designed to investigate the safety, efficacy and pharmacokinetics of a single dose of baloxavir in pediatric patients 1–<12 years old.14 The baloxavir and oseltamivir arms of the study had a similar incidence and severity of AEs and a comparable TTAS. The TCVS was decreased for baloxavir compared with oseltamivir. Although the risk-benefit profile was considered acceptable, the rate of treatment-emergent amino acid substitutions [polymerase acidic (PA)/I38X] associated with reduced susceptibility to baloxavir was higher in children <5 years old compared with children 5–11 years old.14
This post hoc analysis of miniSTONE-2 evaluated the safety and efficacy of baloxavir compared with oseltamivir in otherwise healthy pediatric patients 5–11 years of age with influenza-like symptoms.
METHODS
Trial Design
The study design has been previously reported.14 Briefly, this was a global, phase 3, multicenter, randomized, double-blind, active-controlled study to assess the safety, pharmacokinetics and efficacy of a single dose of baloxavir granules for oral suspension compared with 5 days of twice-daily oseltamivir treatment in otherwise healthy pediatric patients 1–<12 years old with influenza-like symptoms during the 2018/2019 northern hemisphere influenza season (NCT03629184). Children were enrolled in parallel into 2 cohorts: 1–<5 years old and 5–11 years old; this article reports the 5- to 11-year-old cohort. Enrolled children had a clinical diagnosis of influenza infection consisting of fever (tympanic temperature of ≥38°C) at screening and at least 1 respiratory symptom (either cough or nasal congestion). Exclusion criteria included children with severe influenza symptoms requiring inpatient treatment and those with concurrent infections requiring systemic antiviral therapy at screening. The study consisted of a 5-day treatment period followed by a 24-day safety follow-up period. Children were randomized 2:1 to receive a single dose of oral baloxavir on day 1 (2 mg/kg for those weighing <20 kg and a single dose of 40 mg for those weighing ≥20 kg) or oral oseltamivir twice-daily (30 mg for patients weighing ≤15 kg, 45 mg for >15–≤23 kg, 60 mg for >23–≤40 kg and 75 mg for >40 kg) on days 1–5. Acetaminophen was permitted for severe influenza symptoms.
This study was conducted in accordance with the Declaration of Helsinki and Good Clinical Practice (ICH E6) guidelines and was approved by all relevant institutional review boards and/or ethics committees at each center. All parents/caregivers of participants gave written informed consent, and child consent was obtained where applicable.
Outcomes
Outcomes in both arms for the full study population have been reported previously.14 The safety end point was the incidence, severity and timing of AEs, serious AEs, vital signs and clinical laboratory test results. Grades are based on the National Cancer Institute Common Terminology Criteria for Adverse Events. Treatment-related AEs were reported by investigators. A key secondary efficacy end point was TTAS, defined as the time from the start of treatment to when all of the following criteria were met and remained so for ≥21.5 hours: score of 0 (no problem) or 1 (minor problem) for cough and nasal symptoms (items 14 and 15 of the Canadian Acute Respiratory Illness and Flu Scale); “yes” response to the following question on the Canadian Acute Respiratory Illness and Flu Scale: “Since the last assessment has the subject been able to return to day care/school, or resume normal daily activity in the same way as performed prior to developing the flu?”; and first return to afebrile state (tympanic temperature <37.2°C). Additional secondary efficacy end points included duration of fever, duration of symptoms, time to return to normal health and activity, frequency of influenza-related complications and proportion of children requiring antibiotics. The secondary virologic end points were TCVS by virus titer and change from baseline in influenza virus titer. Exploratory virologic end points included frequency of treatment-emergent amino acid substitutions.17 Baseline samples from both groups were also tested for coinfections, using the BioFire FilmArray Respiratory Panel 2 assay.19
Statistical Analysis
Analyses were not powered for statistical comparisons between baloxavir and oseltamivir. For the efficacy analysis where time to event and proportion of children with events are presented, an event is defined as the specific end point of interest. Patients with no alleviation of signs and symptoms were censored at their last assessment. The safety population included all children who received any portion of a single dose regardless of whether they had any follow-up visits and was used for all safety analyses. The intent-to-treat influenza-infected (ITTi) population included all children who received any portion of a single dose and had laboratory confirmation of influenza infection (reverse transcriptase–polymerase chain reaction) from any swab sample collected at baseline or during the study. The ITTi population was used for all efficacy analyses. All comparisons for safety and efficacy are descriptive.
A sensitivity analysis was performed post hoc to evaluate the impact of the “return to normal health and activity” component on TTAS, with the following criterion removed: a “yes” response to “Since the last assessment has the subject been able to return to day care/school or resume his or her normal daily activity in the same way as performed prior to developing the flu?” The other 2 criteria as described were included.
Polymorphic and treatment-emergent amino acid substitutions in the PA, PB1, PB2 and neuraminidase genes were assessed.
RESULTS
Patient Disposition and Baseline Characteristics
A total of 120 children 5–11 years of age were randomized, and 118 children received ≥1 dose of treatment, 79 (99%) in the baloxavir group and 39 (98%) in the oseltamivir group (Fig. 1). In each group, 95% of children completed the study.
FIGURE 1.
Patient disposition. ITTi indicates intent-to-treat influenza-infected; RT-PCR, reverse transcriptase–polymerase chain reaction.
Baseline characteristics were similar between the groups in the safety population (Table 1). The majority were White (baloxavir 90%; oseltamivir 87%), not Hispanic or Latino (52% vs. 56%) and not vaccinated (48% vs. 56%). Median age was 8.0 years (range, 5–11 years) overall and in each group. Of children with known influenza subtype, the most frequent was H3 (65% baloxavir vs. 71% oseltamivir). Concomitant medications were comparable between groups (86% baloxavir vs. 95% oseltamivir), with the most common being nervous system analgesics, acetaminophen and ibuprofen.
TABLE 1.
Baseline Characteristics of the Safety Population
| Baloxavir Marboxil (n = 79) | Oseltamivir (n = 39) | All (N = 118) | |
|---|---|---|---|
| Age, years | |||
| Mean (SD) | 7.7 (1.93) | 7.8 (2.06) | 7.7 (1.97) |
| Median | 8.0 | 8.0 | 8.0 |
| Min-max | 5–11 | 5–11 | 5–11 |
| 5–<12, n (%) | 79 (100) | 39 (100) | 118 (100) |
| Sex, n (%) | |||
| Female | 44 (56) | 22 (56) | 66 (56) |
| Male | 35 (44) | 17 (44) | 52 (44) |
| Ethnicity, n (%) | |||
| Hispanic or Latino | 38 (48) | 17 (44) | 55 (47) |
| Not Hispanic or Latino | 41 (52) | 22 (56) | 63 (53) |
| Race, n (%) | |||
| American Indian or Alaskan native | 1 (1) | 0 | 1 (1) |
| Black or African American | 1 (1) | 3 (8) | 4 (3) |
| Native Hawaiian or other Pacific Islander | 0 | 1 (3) | 1 (1) |
| White | 71 (90) | 34 (87) | 105 (89) |
| Multiple | 2 (3) | 0 | 2 (1.7) |
| Unknown | 4 (5) | 1 (3) | 5 (4) |
| Weight, kg | |||
| Mean (SD) | 30.9 (11.8) | 34.8 (15.2) | 32.2 (13.1) |
| Median | 28.6 | 29.5 | 28.6 |
| Min-max | 13.4–64.4 | 18.2–84.9 | 13.4–84.9 |
| Vaccinated, n (%) | |||
| Yes | 41 (52) | 17 (44) | 58 (49) |
| No | 38 (48) | 22 (56) | 60 (51) |
| Virus subtype, n (%) | |||
| n | 57 | 31 | 88 |
| A/H1N1pdm09 | 10 (18) | 7 (23) | 17 (19) |
| A/H3N2 | 37 (65) | 22 (71) | 59 (67) |
| B | 5 (9) | 2 (7) | 7 (8) |
| A/H1N1pdm09/B | 1 (2) | 0 | 1 (1) |
| Unknown | 4 (7) | 0 | 4 (5) |
| Coinfection with another infectious pathogen, n (%) | 18 (30) | 5 (15) | 23 (25) |
Safety
The incidence of AEs was balanced between baloxavir (44% of children and 50 events) and oseltamivir (44%; 20 events). AEs related to treatment were 3% for baloxavir (rash and accidental overdose of oseltamivir placebo) and 3% for oseltamivir (vomiting). All AEs were grade 1 or 2 in either group. The most frequently (≥5%) reported AEs in baloxavir versus oseltamivir were vomiting (5% vs. 18%), diarrhea (5% vs. 0%), otitis media (0% vs. 5%) and medication error (5% vs. 3%), respectively (Table 2). Most AEs (96%) resolved or were resolving at study end with the exception of 3 AEs that were not resolved by study end (day 29): 2 AEs of upper respiratory tract infection starting on day 20 and day 24, and 1 AE of oropharyngeal pain that started on day 24. Two AEs led to withdrawal from treatment in the baloxavir group (accidental overdose and rash), and none led to withdrawal from treatment in the oseltamivir group.
TABLE 2.
Overview of Adverse Events Experienced by >2% of Children in at Least One Treatment Group (Safety Population)*
| Adverse Event (MedDRA Preferred Term), n (%) | Baloxavir Marboxil (n = 79) | Oseltamivir (n = 39) | All (N = 118) |
|---|---|---|---|
| Vomiting | 4 (5) | 7 (18) | 11 (9) |
| Medication error | 4 (5) | 1 (3) | 5 (4) |
| Diarrhea | 4 (5) | 0 | 4 (3) |
| Rhinorrhea | 3 (4) | 1 (3) | 4 (3) |
| Headache | 2 (3) | 1 (3) | 3 (3) |
| Pharyngitis streptococcal | 2 (3) | 1 (3) | 3 (3) |
| Upper respiratory tract infection | 2 (3) | 1 (3) | 3 (3) |
| Accidental overdose | 2 (3) | 1 (3) | 3 (3) |
| Rash | 2 (3) | 0 | 2 (2) |
| Ear pain | 1 (1) | 1 (3) | 2 (2) |
| Abdominal pain | 1 (1) | 1 (3) | 2 (2) |
| Otitis media | 0 | 2 (5) | 2 (2) |
| Asthma | 1 (1) | 1 (3) | 2 (2) |
| Rhinitis allergic | 2 (3) | 0 | 2 (2) |
| Gastroenteritis viral | 0 | 1 (3) | 1 (1) |
| Otitis media acute | 0 | 1 (3) | 1 (1) |
The safety population comprised children 5–11 years of age who received any portion of a single dose of treatment.
MedDRA indicates Medical Dictionary for Regulatory Activities.
No serious AEs, hospitalizations or deaths occurred.
No clinically meaningful changes from baseline were observed for any laboratory parameters, and no clinically meaningful differences were observed between groups for vital signs.
The incidence of influenza-related complications was similar in both groups: 3 (4.9%) children in the baloxavir group and 1 (3.0%) in the oseltamivir group. Otitis media occurred in 1 child each in the baloxavir and oseltamivir groups, and sinusitis and bronchitis occurred in 1 child each in the baloxavir group. One child each in the baloxavir and oseltamivir groups received antibiotics for sinusitis and otitis media, respectively.
Efficacy
Median TTAS was comparable between the 2 treatment groups: 138.4 hours (95% CI: 116.7–163.4) for the baloxavir group compared with 126.1 hours (95% CI: 95.9–165.7) for oseltamivir (Table 3 and Fig. 2). In the TTAS sensitivity analysis, median TTAS was shorter in both groups compared with the original TTAS definition: median 69.8 hours (95% CI: 44.2–94.9) for the baloxavir group compared with 71.1 hours (95% CI: 55.4–118.2) for the oseltamivir group (Fig. 2). Kaplan-Meier curves were also similar between groups for TTAS and the sensitivity analysis (Fig. 2). Subgroup analyses of median TTAS by viral subtype showed comparable efficacy between baloxavir and oseltamivir for viral subtype H3N2 [128.7 hours (95% CI: 92.3–163.2) vs. 111.6 hours (71.3–158.1)], and alleviation was numerically lower in the baloxavir group for viral subtype H1N1pdm09 than in the oseltamivir group [140.3 hours (77.3–192.3) vs. 165.7 hours (63.4–not estimable)] (Table 3); however, the low number of patients with H1N1pdm09 limits the interpretation of these data. The numbers of patients with other viral subtypes were too low to interpret those data.
TABLE 3.
Overview of Secondary Efficacy and Virologic End Points in the ITTi Population*
| Baloxavir Marboxil (n = 61) | Oseltamivir (n = 33) | |
|---|---|---|
| Efficacy | ||
| Evaluable children, n | 56 | 27 |
| Median TTAS, h (95% CI) | 138.4 (116.7–163.4) | 126.1 (95.9–165.7) |
| Evaluable children, n | 34 | 20 |
| In patients with H3N2 infection (95% CI) | 128.7 (92.3–163.2) | 111.6 (71.3–158.1) |
| Evaluable children, n | 10 | 4 |
| In patients with H1N1pdm09 infection (95% CI) | 140.3 (77.3–192.3) | 165.7 (63.4–NE) |
| Evaluable children, n | 60 | 31 |
| Median duration of fever, h (95% CI) | 66.4 (41.7–76.4) | 56.0 (41.2–78.5) |
| Virology | ||
| Patients with a postbaseline virology assessment, n | 48 | 29 |
| Evaluable children, n | 48 | 28 |
| TCVS, h (95% CI) | 24.1 (23.3–24.6) | 75.8 (69.3–95.6) |
The ITTi population comprised children 5–11 years old who received treatment and had a laboratory RT-PCR confirmation of influenza infection from any swab sample collected at baseline or during the study.
ITTi indicates intent-to-treat influenza-infected; NE, not evaluable; RT-PCR, reverse transcriptase–polymerase chain reaction; TCVS, time to cessation of viral shedding; TTAS, time to alleviation of symptoms.
FIGURE 2.
Kaplan-Meier plots of (A) time to cessation of viral shedding by virus titer, (B) time to alleviation of symptoms (4 patients in the baloxavir group and 6 in the oseltamivir group were censored) and (C) sensitivity analysis of time to alleviation of symptoms per treatment group in the intent-to-treat influenza-infected population. NE indicates not evaluable.
The median duration of fever [baloxavir: 41.2 hours (95% CI: 23.5–51.4) vs. oseltamivir 51.3 hours (95% CI: 30.7–56.8)] (Table 3), median duration of all symptoms [66.4 hours (95% CI: 41.7–76.4) vs. 56.0 hours (95% CI: 41.2–78.5)] and median time to return to normal activity [118.2 hours (95% CI: 94.8–138.6) vs. 111.1 hours (95% CI: 80.8–118.7)] were comparable between groups.
Virology
The median TCVS by virus titer was shorter in the baloxavir group [24.1 hours (95% CI: 23.3–24.6)] compared with the oseltamivir group [75.8 hours (95% CI: 69.3–95.6); Table 3 and Fig. 2]. The Kaplan-Meier curves show a separation of the curves for each treatment after 24 hours (Fig. 2).
A greater decline in the mean change from baseline in influenza virus titer was observed in the baloxavir group on day 2 compared with the oseltamivir group. The mean change from baseline reached a plateau by day 2 for the baloxavir group [–3.45 log10 median tissue culture infectious dose (TCID50)/mL (SD 1.38)] compared with the oseltamivir group on the same day [–1.85 log10 TCID50/mL (SD 1.50)]. In the oseltamivir group, the mean change from baseline plateaued after day 3. At later time points, the differences from baseline in each group were comparable.
Overall, 23 of 94 (24.5%) children in the ITTi population had a coinfection [baloxavir: 18/61 (29.5%); oseltamivir: 5/33 (15.2%)]. In the baloxavir group, 16 children with influenza A had a coinfection: 9 had a subtype of coronavirus (either 229E, HKU1, OC43, or NL63), 3 children each had rhinovirus/enterovirus and respiratory syncytial virus and 1 child had influenza B. Two children with influenza B receiving baloxavir had a coinfection, 1 with rhinovirus/enterovirus and 1 with both adenovirus and rhinovirus/enterovirus. In the oseltamivir group, 4 children with influenza A had coinfection: 2 had rhinovirus/enterovirus and 2 had coronavirus (NL63). One child with influenza B receiving oseltamivir had rhinovirus/enterovirus.
None of the 53 children 5–11 years old with sequenced baseline samples had preexisting I38X mutations, which are associated with reduced susceptibility to baloxavir.20 Of 41 children treated with baloxavir and with paired (pre and postdose) samples, 6 (14.6%) had treatment-emergent I38X substitutions. In influenza subtype H3N2, 1 child had I38T, 2 had I38T/I mixtures and 1 had I38T, which converted into I38M at a later time point. Two children infected with subtype H1N1 had I38X substitutions: 1 had I38T and 1 had a mixture of I38S/I. None of the patients with influenza B infection were found to have any amino acid substitutions in PA variants. Twelve children had no detectable or low levels of virus after treatment that did not allow for sequencing.
DISCUSSION
In this post hoc analysis of miniSTONE-2 in children 5–11 years of age, there was high study completion with 95% of children in each group completing the trial. However, in a real-world study using US data from the 2019 to 2020 flu season, 27% of patients did not complete their antiviral treatment, which was primarily neuraminidase inhibitors.21 In other real-world studies, between 14% and 21% of patients with influenza did not complete the full course of oseltamivir, indicating these clinical trial results may show a higher number of children who completed oseltamivir treatment versus real-world experience.22,23
Treatment with baloxavir was generally well tolerated. No significant safety concerns or signals were identified when administered to pediatric patients 5–11 years old with influenza-like symptoms. The incidence of AEs related to study drug was balanced in the baloxavir and oseltamivir groups, with the most common being vomiting (5.1% vs. 17.9%), diarrhea (5.1% vs. 0%) and otitis media (0% vs. 5.1%), respectively. In these 5- to 11-year-olds, post hoc analysis safety results were consistent with those from the overall miniSTONE-2 trial population.14
The efficacy results were comparable between the 2 treatment groups including TTAS, fever, duration of symptoms, complications and the proportion of patients requiring antibiotics. The post hoc TTAS sensitivity analysis revealed a lower TTAS in both treatment groups compared with the original TTAS definition, with a numerically lower median in the baloxavir group compared with the oseltamivir group. Since the TTAS sensitivity analysis removed a “yes” response to the question “Since the last assessment has the subject been able to return to day care/school or resume his or her normal daily activity in the same way as performed prior to developing the flu?,” this indicates that “return to normal health and activity” is the factor most likely contributing to the longer time. Of note, 23 children had a coinfection with another respiratory virus at baseline, and given the small number of patients with coinfections, no formal statistical analyses on the impact of baseline coinfection on TTAS were conducted. Combined with the fact that there are no coinfection data available after baseline, it is unknown whether coinfections at baseline or during the study contributed to a longer TTAS versus those patients who did not experience any coinfection. All efficacy end points of TTAS, duration of fever, duration of all symptoms and time to return to normal activity were comparable with those from the overall miniSTONE-2 trial population,14 no differences were seen between this analysis and the overall population for the incidence of influenza-related complications or the use of antibiotics.
Baloxavir had a more rapid decline in infectious viral titer compared with oseltamivir, as measured by TCVS (1 day for baloxavir vs. ≈3 days for oseltamivir) and change from baseline in influenza titer; these results were similar to those in the overall trial population and previous baloxavir studies.13–15
The treatment-emergent PA/I38T substitution and additional I38 amino acid substitutions (PA/I38M, PA/I38F, PA/I38S and PA/I38N), collectively referred to as PA/I38X, are associated with reduced baloxavir susceptibility.20 In previous studies and the miniSTONE-2 trial population, higher prevalence rates of PA/I38X viral variants were observed in children <5 years old compared with children ≥5 years old.14,17,18 The rates of I38X viral variants in this study with children 5–11 years old were consistent with those observed previously in baloxavir pediatric studies in children ≥5 years of age.17,18
A limitation of this study is that it is a post hoc analysis of the miniSTONE-2 study, which was not powered for a statistical comparison between the treatment arms. Another limitation is that many enrolled children were White; because influenza may disproportionately affect racial and ethnic minority groups, further real-world studies should examine these treatments in different racial and ethnic populations.24
The risk-benefit profile for baloxavir was positive in children 5–11 years old. The safety, efficacy and virology results were similar between patients 5–11 years of age and the overall trial population of patients 1–<12 years old and supports the finding that baloxavir is well tolerated in children.14 In addition, efficacy was comparable between baloxavir and oseltamivir, and baloxavir was associated with a more rapid decline in infectious viral titer versus oseltamivir. Single-dose baloxavir provides an additional treatment option for pediatric patients 5–11 years old with influenza.
Supplementary Material
Footnotes
This post hoc analysis was funded by F. Hoffmann LaRoche Ltd and Genentech, Inc., and this funding contributed to the trial design, data interpretation and writing of this report. The authors thank Denise Kenski, PhD, of Health Interactions, Inc, for providing editorial assistance, which was funded by F. Hoffmann LaRoche Ltd and Genentech, Inc., in accordance with Good Publication Practice (GPP2022) guidelines (https://www.ismpp.org/gpp-2022). S.E.C., C.C., M.S., S.S. and S.W. are the employees of Genentech, Inc, and hold shares of Roche. L.B.M. is the employee of Roche Products Ltd and holds shares of Roche. The other authors have no conflicts of interest to disclose.
Qualified researchers may request access to individual patient-level data through the clinical study data request platform (https://vivli.org/). Further details on Roche’s criteria for eligible studies are available here (https://vivli.org/members/ourmembers/). For further details on Roche’s Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).
All authors contributed to, reviewed and approved the final draft of the article. All authors had full access to all the data in the study and had final responsibility for the decision to submit for publication. J.B.B. and S.L.B. coordinated and supervised data collection, and reviewed and revised the article. S.E.C. and L.B.M. provided critical revision of the article for important intellectual content. C.C. and M.S. provided critical revision of the article for important intellectual content and drafting of the article. S.S. and S.W. carried out the initial analyses and reviewed and revised the article. All authors approved the final article as submitted and agree to be accountable for all aspects of the work.
The supplemental visual abstract associated with this article is available at http://links.lww.com/INF/F286.
Contributor Information
Stanley L. Block, Email: slblockmd@hotmail.com.
Steven E. Cagas, Email: cagas.steven@gene.com.
Laura Burleigh Macutkiewicz, Email: laura.macutkiewicz@roche.com.
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Mitra Sadeghi, Email: sadeghi.mitra@gene.com.
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