Baloxavir Marboxil Significantly Reduces Time to Improvement of Flu Complications

Baloxavir marboxil has been shown to significantly cut the time to improvement of flu symptoms compared with placebo in patients deemed to be at high risk of serious complications from influenza. The treatment was also found to be well-tolerated with no new safety signals observed.

Results from the phase 3 CAPSTONE-2 study were presented by Michael G. Ison, MD, MS, FIDSA, a professor at Northwestern University Feinberg School of Medicine, in a Late Breaker Oral Abstract session at ID Week 2018.

Discovered by Shionogi & Co., Ltd., and further developed and commercialized by Roche Group, baloxavir marboxil is a first-in-class, investigational medicine to be taken by mouth via a single dose, with a novel mechanism of action.

“I think the most important feature of baloxavir is that it’s a new class of antiviral medications for influenza,” Dr. Ison told Contagion^® in an exclusive interview. “The currently approved medications that are available to us are the m2 inhibitors that inhibit the m2 ion channel and the neuraminidase inhibitors that inhibit the neuraminidase. Baloxavir affects the flow rates in the PA segment, and therefore, is active against viruses that may be resistant to either the neuraminidase or the m2 ion channel.”

For the phase 3, multicenter, randomized, double-blind trial, investigators set out to evaluate how safe and effective baloxavir marboxil would be in comparison with oseltamivir or placebo in individuals 12 years of age or older with high risk of complications from the flu. These individuals included those 65 years of age or older or those with conditions such as asthma, chronic lung disease, morbid obesity, or heart disease.

The investigators enrolled 2184 participants in the trial and randomized (1:1:1) them to receive either a single, oral dose of 40 mg or 80 mg of baloxavir marboxil (in accordance with body weight), placebo, or oseltamivir 75 mg, twice daily for the duration of 5 days.

Of the 2184 participants, 1163 were confirmed to be infected with influenza via the use of reverse transcription polymerase chain reaction (RT-PCR) testing. Of those with confirmed influenza infections, 47.9% had subtype A/H3N2, 6.9% had A/H1N1, and 41.6% had subtype B.

Dr. Ison added that the most common risk factors observed in participants were asthma or chronic lung disease (39.2%), being 65 years of age or older (27.4%), endocrine disorders (32.8%), metabolic disorders (13.5%), heart disease (12.7%), and morbid obesity (10.6%).

The investigators found that baloxavir marboxil significantly reduced the time to improvement of flu symptoms in patients with high risk of serious complications compared with placebo (median time of 73.2 hours vs 102.3 hours, p<.0001). Specifically, when it came to patients with influenza type A/H3N2, the investigative treatment demonstrated efficacy of reducing time to improvement of flu symptoms compared with placebo (median time of 75.4 hours vs 100.4 hours, p<.05); it was also effective in those with influenza B compared to placebo (median time of 74.6 hours vs 100.6 hours; p<.05).

In the overall patient population, those who received baloxavir marboxil demonstrated a shorter time to improvement of flu symptoms compared with oseltamivir, with a median time to improvement of 73.2 hours versus 81.0 hours, respectively, p=.8347).

The investigators highlight that when looking specifically at a subset of patients with influenza B—a subgroup for which some antiviral treatments only show limited efficacy&mdash;baloxavir marboxil was found to be “significantly efficacious” compared with oseltamivir in cutting time to improvement of flu symptoms (median time of 74.6 hours vs 101.6 hours, p<.05).

The virologic clearance was faster in the patients who received baloxavir marboxil compared with oseltamivir and placebo (viral shedding; median time of 48.0 hours, 96.0, 96.0, p<.0001, respectively). The investigative treatment was also found to cut the use of antibiotics and incidence of flu complications (3.4% and 2.8%, respectively) in comparison with placebo (7.5% and 10.4%; p=.01, p<.05).

“The patients tolerated the medicine very well,” Dr. Ison said, adding that there was a lower overall incidence of adverse events in those who received baloxavir marboxil (25.1%), compared with placebo or oseltamivir (29.7% and 28%, respectively).

In our interview, Dr. Ison discussed the important takeaways from the study (see video).

“Most importantly, it will bring a therapy that only requires a single dose, so, patients will be able to take a pill and will be done taking the medication for the treatment for influenza,” he concluded. “And after taking it, they will be at reduced risk for complications, including those requiring antibiotics or other complications of influenza.”