What is influenza?
Influenza is a serious illness of the respiratory tract caused by viruses. Infection can occur through minute droplets in the air we breathe or through contact with contaminated surfaces. Since the pathogens, influenza A and B viruses, can change rapidly (i.e. high mutation rate), no lasting immune protection can develop in humans, which means that infection can occur several times. While A viruses (higher mutation rate) can lead to a severe course, B viruses (lower mutation rate) usually provoke a milder course of the disease. The most common symptoms include: sudden onset of fever with chills, bone pain, sore throat, headache and irritable cough. Normally, treatment is by bed rest and only symptomatic with pain and fever medications such as ibuprofen, paracetamol or Baloxavir marboxil.
New drug Baloxavir marboxil:
Baloxavir marboxil (hereafter referred to as baloxavir) is an antiviral agent that was approved in 2018 in the United States and Japan, and in 2020 in Switzerland in the form of film-coated tablets for the treatment of uncomplicated influenza in otherwise healthy individuals 12 years of age and older. This drug is a selective inhibitor as an early step in the replication cycle of the virus is inhibited. The study, published in 2020, in the journal The Lancet Infectious Diseases, thereby examined the efficacy of baloxavir in outpatients at high risk for developing influenza-associated complications.
The randomized, double-blind, placebo-controlled phase 3 study was conducted in outpatients 12 years of age and older at 551 sites in 17 countries. Eligible participants were diagnosed with influenza-like illness, had a risk factor for influenza-associated complications (ie: older than 65 years) and symptom duration of less than two days. Patients were classified using the following factors: Baseline symptoms, existing and worsened symptoms at onset compared to before influenza, geographic region (Asia, Europe, North America, or Southern Hemisphere), and weight (either more or less than 80 kg).
Three groups were randomized: The first group (N=730) received a single dose of 40 mg baloxavir if body weight was less than 80 kg or 80 mg of the drug if body weight was 80 kg or more. A second group (N=725) was given 75 mg oseltamivir (i.e., drug used for viral influenza therapy) twice daily for 5 days. The control group (N=729) received matching placebo. The primary endpoint was time to improvement of influenza symptoms (i.e., Time to Improvement of Influenza Symptoms, or TTIIS).
Of the 2184 patients studied between January 2017 and March 2018, 1163 study participants entered the so-called modified intention-to-treat analysis (ITT for short). This is a medical statistics procedure that requires retrospective analysis of data from all patients who were previously intended to be treated. In this analysis 48% of the ITT patients had influenza virus A H3N2. 42% were infected with influenza B and 7% with influenza A H1N1 virus. The remaining influenza viruses were mixed (14 patients) or not more precisely identified influenza subtypes (28 patients). The mean TTIIS was significantly shorter in the baloxavir group (73.2 hours) than in the control group with placebo (102.3 hours TTIIS). The second group (oseltamivir group) showed a mean of 81.0 hours in the results.
Adverse effects were not significantly different among the three study groups, with the baloxavir group experiencing adverse effects in 25% of participants (oseltamivir in 28% and the placebo group in 30%). Serious adverse effects were very rare in all three groups (no more frequent in the baloxavir group than in the other two groups).
According to the study studies, a single dose of baloxavir has significantly superior efficacy to placebo and similar efficacy to the alternative drug oseltamivir in relieving influenza symptoms in high-risk outpatients 12 years of age and older. The safety of baloxavir was also comparable to placebo in the study. By reducing influenza complications in high-risk patients, this treatment therapy could potentially accelerate clinical recovery and thereby support this same risk early.