Baloxavir marboxil (1) – Xofluza®

• Clinical trials
  • The JapicCTI-153090 trial is a double-blind RCT comparing baloxavir marboxil with placebo, in which 400 participants aged ≥ 20 to < 65 years with influenza confirmed by an antigen test were enrolled.
  • The multicentre, double-blind RCT CAPSTONE-1 enrolled 1,436 participants, similar to the JapicCTI-153090, who had a symptomatically diagnosed influenza infection, were aged between 12 and ≤ 64 years, and had no risk factors for influenza-related complications; they were randomised in a 2:2:1 ratio to the three study arms: baloxavir marboxil, placebo and oseltamivir.
  • The multicentre, double-blind RCT CAPSTONE-2 enrolled approximately 2,200 patients with symptomatically diagnosed influenza infection, as in the CAPSTONE-1 and at least one risk factor for influenza-related complications, aged 12 years and over, were randomised in a 1:1:1 ratio to three study arms (placebo, oseltamivir and baloxavir marboxil).

a) Adults and adolescents aged 12 years and over with influenza who are not at risk of influenza-related complications

• For adults and adolescents aged 12 years and over with influenza who are not at risk of influenza-related complications, the additional benefit of baloxavir marboxil compared with the appropriate comparator therapy is not proven.
• The G-BA has defined symptomatic treatment (antipyretics, anti-inflammatory drugs, analgesics) as the appropriate comparator therapy for this patient group.
• In the JapicCTI-153090 and CAPSTONE-1 studies, symptomatic treatment with antipyretics and analgesics (with the exception of paracetamol) as well as other symptomatic treatments such as, for example, cough suppressants and expectorants or combination cold remedies.
• Overall, it is unclear how many people would have used symptomatic treatment to relieve their symptoms, and how frequently they would have done so, had the restriction described in the study protocol not been in place.
• Due to the restriction on the use of symptomatic treatment imposed by the trial protocol, it is not possible to draw conclusions regarding the additional benefit in either trial for patient-relevant endpoints relating to influenza symptoms and health status.
• Consequently, the pharmaceutical manufacturer did not submit a study for this patient population that would have been suitable for assessing the additional benefit of baloxavir marboxil compared with the appropriate comparator therapy.

b) Adults and adolescents aged 12 years and over with influenza, where there is an increased risk of severe disease

• For adults and adolescents aged 12 years and over with influenza who are at increased risk of severe disease, the additional benefit of baloxavir marboxil compared with oseltamivir is not proven.
• mortality
  • For the endpoint of overall survival, no statistically significant difference was observed between baloxavir marboxil and oseltamivir.
• morbidity
  • For the overall population relevant to the assessment, a shift in the effect towards a null effect is to be expected compared with the effect in the ITTI population.
• Overall assessment
  • Uncertainties arise in the study regarding the additional symptomatic adjunctive therapy available, which was severely restricted due to the limitations set out in the study protocol.
  • In the overall review of the results in the morbidity category regarding the endpoints of influenza symptoms, health status and influenza-typical complications, no statistically significant difference was observed between baloxavir marboxil and oseltamivir in the additionally presented ITTI population.
  • In summary, for adults and adolescents aged 12 years and over with influenza who are at increased risk of a severe course of the disease, an overall assessment of the results on mortality, morbidity and side effects shows no additional benefit of baloxavir marboxil compared with oseltamivir.

Courtesy translation only, please refer to the German original.