Roche’s Xofluza Set for EU Approval: First New Flu Drug in 20 Years Offers Single-Dose Cure Within 24 Hours

November 15, 2020 News /Bio ValleyBIOON/ -- Roche recently announced that the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA) has issued a positive opinion, recommending the approval of Xofluza for: (1) the treatment of uncomplicated influenza in patients aged ≥12 years; and (2) post-exposure prophylaxis for the prevention of influenza in individuals aged ≥12 years.

The CHMP opinion will now be submitted to the European Commission (EC) for review, which is expected to make a final decision within the next two months. If approved, Xofluza will become the first anti-influenza drug with an innovative mechanism of action approved in the EU in nearly 20 years. InClinical TrialsIn China, a single dose of Xofluza significantly reduces the duration of influenza symptoms and markedly decreases viral shedding within just one day.

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, millions of hospitalizations, and up to 650,000 deaths annually.

Xofluza is a first-in-class, single-dose oral medication with a novel mechanism of action against influenza. 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 designed to combat both influenza A and B viruses, including oseltamivir-resistant strains andAvian InfluenzaStrains (H7N9, H5N1).

Asthma, patients with chronic lung disease, heart disease, or morbid obesity, or elderly individuals aged ≥65 years.

Xofluza is the first and only single-dose oral medication approved for the treatment of influenza, and it is also the first novel anti-influenza drug with a new mechanism of action in nearly 20 years.Robust clinical evidence demonstrates the therapeutic benefits of Xofluza across multiple populations (healthy individuals with influenza, high-risk populations for influenza complications, and children) and treatment settings (symptomatic influenza and post-exposure prophylaxis). Currently, Xofluza is being evaluated in a Phase III clinical development program, which includes studies in infants under one year of age (NCT03653364), hospitalized patients with severe influenza (NCT03684044), and an assessment of the potential to reduce influenza transmission from infected individuals to healthy contacts (NCT0396912).

The CHMP’s positive opinion is based on the results of the Phase 3 CAPSTONE-1, CAPSTONE-2, and BLOCKSTONE studies.

——CAPSTONE-1 Study:A total of 1,436 cases were enrolled.DiagnosisIn otherwise healthy patients with influenza (aged ≥12 years), a single dose of Xofluza was compared with placebo and the anti-influenza drug oseltamivir (brand name: Tamiflu, 75 mg twice daily for 5 days). The results showed that, compared with placebo, Xofluza significantly shortened the duration of influenza symptoms (median time: 53.7 hours vs. 80.2 hours, p<0.0001) and significantly reduced the duration of fever (median time: 24.5 hours vs. 42.0 hours, p<0.0001). Furthermore, compared with both placebo and oseltamivir, Xofluza significantly shortened the duration of viral shedding (median time: 24.0 hours for Xofluza, 96.0 hours for placebo, and 72.0 hours for oseltamivir; p<0.0001). In this study, Xofluza was well tolerated, with an overall incidence of adverse events slightly lower than that observed in the placebo and oseltamivir groups.

——CAPSTONE-2 Study:A total of 2,184 high-risk subjects aged ≥12 years with influenza complications were enrolled to compare single-dose Xofluza (40 mg or 80 mg, based on body weight) with placebo or oseltamivir (75 mg twice daily for 5 days). The results showed that, compared with placebo, Xofluza significantly shortened the time to alleviation of influenza symptoms (median time: 73.2 hours vs. 102.3 hours, p<0.0001). In patients with influenza B, Xofluza demonstrated superior efficacy compared with both placebo and Tamiflu in shortening the time to alleviation of influenza symptoms (median times: 74.6 hours, 100.6 hours, and 101.6 hours, respectively; p=0.0138 and p=0.0251). Furthermore, compared with placebo, Xofluza significantly reduced the time to defervescence, lowered the incidence of influenza-related complications, and decreased systemicAntibioticsCessation of Viral Shedding. Compared with oseltamivir, Xofluza significantly shortened the duration of viral shedding (median time: 48 hours vs. 96 hours; p < 0.0001). In this study, Xofluza was well tolerated, with an overall incidence of adverse events slightly lower than that in the placebo and oseltamivir groups.

——BLOCKSTONE Study:is a randomized, placebo-controlled, post-exposure prophylaxis study enrolling healthy subjects (adults and children) whose family members tested positive for influenza via rapid influenzaDiagnosisThe test confirmed influenza infection (i.e., the “index patient”). These subjects were randomly assigned to receive a single dose of Xofluza (dose adjusted by body weight) or placebo as a measure to prevent influenza occurrence. The primary endpoint was to evaluate the proportion of subjects who tested positive for influenza virus, had fever, and experienced one or more respiratory symptoms during the observation period from Day 1 to Day 10.

The results showed that in healthy subjects with household members suffering from influenza, a single oral dose of Xofluza had a significant preventive effect against influenza infection, reducing the risk of developing influenza by 86%. Specifically, compared to the placebo group, the proportion of subjects who developed influenza infection in the Xofluza group was significantly reduced (proportion of subjects experiencing influenza virus infection, fever, and other flu symptoms during the 10-day observation period: 1.9% vs 13.6%, p < 0.0001). Regardless of the influenza A subtype, the therapeutic benefit of Xofluza remained statistically significant compared to placebo (H1N1 subtype: 1.1% vs 10.6%, p = 0.0023; H3 subtype: 2.8% vs 17.5%, p < 0.0001). Additionally, this effect was also observed among household contacts at higher risk for influenza-related complications (2.2% vs 15.4%, p = 0.0435) and children under 12 years old (4.2% vs 15.5%, p = 0.0339), who are more susceptible to contracting influenza. The study further demonstrated that even when applying less stringent criteria for influenza (proportion of participants with influenza, fever, or one or more respiratory symptoms), Xofluza still significantly reduced the risk of household members contracting influenza by 76% compared to placebo (3% vs 22.4%, p < 0.0001). In the study, the safety profile of Xofluza was comparable to that of placebo, with adverse event rates of 22.2% in the Xofluza group and 20.5% in the placebo group. No serious adverse events were reported for Xofluza. (Bioon.com)

Original source: CHMP recommends EUapproval of Roche’s Xofluza® (baloxavir marboxil) for the treatment of influenza