The US FDA has accepted a supplemental New Drug Application (sNDA) for Xofluza (baloxavir marboxil) as a single-dose, oral treatment for people at high risk of complications from the flu, according to Genentech.
The CDC defines people at high risk for serious flu complications to include adults 65 years of age or older, or those who have conditions such as asthma, chronic lung disease, morbid obesity or heart disease.
The FDA is expected to make a decision on approval by November 4, 2019.
The sNDA is based on results from the Phase III CAPSTONE-2 study of a single dose of Xofluza compared with placebo or oseltamivir 75 mg, twice daily for five days, in people 12 years of age or older who are at high risk of complications from the flu.
The FDA approved Xofluza in October 2018 for the treatment of acute, uncomplicated influenza in people 12 years of age or older. It is the first and only single-dose oral medicine approved to treat the flu, and the first new flu medicine with a novel proposed mechanism of action in nearly 20 years.
CAPSTONE-2 is a Phase III multicenter, randomized, double-blind study that evaluated the efficacy and safety of a single dose of Xofluza compared with placebo and oseltamivir in 2,184 people 12 years of age or older who are at high risk of complications from the flu. The primary objective of the study evaluated the efficacy of a single dose of Xofluza compared with placebo by measuring the time to improvement of influenza symptoms. Important secondary endpoints compared outcomes in Xofluza versus placebo or oseltamivir, including time to resolution of fever, time to cessation of viral shedding, infectious virus detection in swabs of the nose and throat, prescription of antibiotics and influenza-related complications.
The study found that Xofluza:
- Significantly reduced the time to improvement of influenza symptoms versus placebo in people at high risk of complications from influenza (median time 73.2 hours versus 102.3 hours; p<0.0001);
- Demonstrated superior efficacy (reduced time to improvement of influenza symptoms) versus placebo and oseltamivir in influenza type B (median time of 74.6 hours versus 100.6 hours and 101.6 hours, respectively (p=0.0138, p=0.0251);
- Demonstrated efficacy for secondary endpoints compared to placebo:Significantly reduced the time to resolution of fever (median time of 30.8 hours versus 50.7 hours; p<0.0001), the incidence of influenza-related complications (2.8 percent versus 10.4 percent; p<0.05), the use of systemic antibiotics (3.4 percent versus 7.5 percent; p=0.01) and the length of time the virus continued to be released from the body (viral shedding; median time of 48 hours versus 96 hours; p<0.0001).
- Similar efficacy results were seen between XOFLUZA and oseltamivir for several secondary endpoints, but a significant difference was observed in the time to cessation of viral shedding favoring XOFLUZA:No significant reduction in the time to resolution of fever (median time of 30.8 hours for XOFLUZA versus 34.3 hours for oseltamivir; p<0.2425), the incidence of influenza-related complications (2.8 percent for XOFLUZA versus 4.6 percent for oseltamivir; p=0.2558) and the use of systemic antibiotics (3.4 percent for XOFLUZA versus 3.9% for oseltamivir; p=0.8478).
- Significantly reduced the length of time the virus continued to be released from the body (viral shedding; median time of 48 hours versus 96 hours; p<0.0001).
In CAPSTONE-2, Xofluza was well tolerated, with no safety signals identified. Xofluza had a numerically lower overall incidence of reported adverse events (25.1%) compared with placebo (29.7%) or oseltamivir (28.0%). The most common adverse events reported in the Xofluza group were bronchitis (2.9%), diarrhea (2.7%), nausea (2.7%) and sinusitis (1.9%).