Roche's Xofluza Receives FDA Priority Review for Expanded Use in High-Risk Flu Patients

Swiss pharmaceutical company Roche recently announced that the U.S. Food and Drug Administration (FDA) has accepted the supplemental New Drug Application (sNDA) for Xofluza (baloxavir marboxil) as a single-dose, oral medication for populations at high risk of influenza complications. The U.S. Centers for Disease Control and Prevention (CDC) defines populations at high risk for severe influenza complications as: adults aged 65 years and older, or those withAsthma, chronic lung disease, morbid obesity, or heart disease.FDAThe final review decision is expected to be made by November 4, 2019.

Sandra Horning, Chief Medical Officer and Global Head of Product Development at Roche, stated, “Influenza can be particularly debilitating for high-risk individuals, as they are more likely to experience severe complications that exacerbate existing health conditions, potentially leading to hospitalization or death. Xofluza is the first antiviral medication with significant clinical benefit for individuals at high risk of influenza-related complications, a population for which no approved treatments currently exist.”

This sNDA is based on the results of the Phase III clinical study CAPSTONE-2. This was a multicenter, randomized, double-blind study conducted in 2,184 individuals aged 12 years and older who were at high risk for influenza complications, evaluating the efficacy and safety of a single dose of Xofluza (40 mg or 80 mg, based on body weight) compared with placebo or Tamiflu (oseltamivir; therapeutic dose: 75 mg twice daily for 5 consecutive days). The primary endpoint was to evaluate the efficacy of single-dose Xofluza versus placebo by measuring the time to alleviation of influenza symptoms (TTAS). Key secondary endpoints included comparisons of outcomes for single-dose Xofluza versus placebo or Tamiflu, such as: time to fever resolution, time to cessation of viral shedding, and detection of infectious virus in nasal and throat swabs from participants.AntibioticsPrescriptions and influenza-related complications.

The results showed that, in high-risk populations for influenza complications, Xofluza significantly shortened the time to alleviation of influenza symptoms compared with placebo (median time: 73.2 hours vs. 102.3 hours; p < 0.0001). Furthermore, among patients with influenza B, Xofluza demonstrated superior efficacy compared with both placebo and oseltamivir (Tamiflu), with median times to symptom alleviation of 74.6 hours, 100.6 hours, and 101.6 hours, respectively (p = 0.0138 and p = 0.0251).

In terms of secondary endpoints, compared with placebo, Xofluza significantly shortened the time to fever resolution (median time: 30.8 hours vs. 50.7 hours, p < 0.0001), reduced the incidence of influenza-related complications (2.8% vs. 10.4%, p < 0.05), and decreased systemicAntibioticsuse (3.4% vs 7.5%, p=0.01) and time to cessation of viral shedding (median time: 48 hours vs 96 hours, p<0.0001). Xofluza demonstrated similar efficacy to Tamiflu across several secondary endpoints, but a significant difference was observed in the time to cessation of viral shedding, favoring Xofluza. Specifically: time to fever resolution (median time: 30.8 hours vs 34.3 hours, p<0.2425), incidence of influenza-related complications (2.8% vs 4.6%, p<0.2558), systemicAntibioticsuse (3.4% vs 3.9%, p=0.8478), time to cessation of viral shedding (median time: 48 hours vs 96 hours, p<0.0001).

In this study, Xofluza was well tolerated, with no safety signals identified. The overall incidence of adverse events reported in the Xofluza group (25.1%) was numerically lower than that in the placebo group (29.7%) or the Tamiflu group (28.0%). The most common adverse events were bronchitis (2.9%), diarrhea (2.7%), nausea (2.7%), and sinusitis (1.9%).

Super Flu Drug Xofluza: Kills Virus Within 24 Hours

Influenza is one of the most common yet serious infectious diseases, posing a significant threat to public health. Globally, influenza causes 3–5 million cases of severe illness annually, results in millions of hospitalizations, and leads to up to 650,000 deaths.

Xofluza was approved in the United States in October 2018FDAApproved for the treatment of acute, uncomplicated influenza in individuals aged 12 years and older. This drug is the first and only single-dose oral medication approved for the treatment of influenza, and it is also the first new anti-influenza drug with a novel mechanism of action to be introduced in nearly 20 years. InClinical TrialIn China, a single dose of Xofluza significantly reduces the duration of influenza symptoms and markedly decreases viral shedding within just one day.

Xofluza is a first-in-class, single-dose oral medication with a novel anti-influenza mechanism of action distinct from other antiviral drugs on the market. As an endonuclease inhibitor, it is designed to inhibit the cap-dependent endonuclease in the influenza virus, an enzyme essential for viral replication. Xofluza is intended to combat influenza A and B viruses, including oseltamivir-resistant strains andAvian Influenzastrains (H7N9, H5N1). Tamiflu, developed by Gilead and commercially promoted globally by Roche, is currently a widely used oral anti-influenza medication. It generally requires continuous administration over several days, with twice-daily dosing, and typically takes 72 hours to take effect. In contrast, Xofluza can kill the influenza virus within 24 hours (although some symptoms may take longer to resolve), and requires only a single oral dose. Suitable for both adults and children, it will lead to a significant improvement in patient adherence.

Xofluza was discovered by the Japanese pharmaceutical company Shionogi and is being co-developed globally by Roche and Shionogi. Under the agreement, Roche holds global rights to the drug, excluding Japan and Taiwan, China. Currently, Xofluza is being evaluated in a Phase III clinical development program that includes pediatric populations, post-exposure prophylaxis, and patients hospitalized with severe influenza, while its potential to reduce transmission in other healthy populations is also under assessment.Bio ValleyBioon.com）