New Flu Drug Cuts Time to Recovery

Marcia Frellick

October 07, 2018

SAN FRANCISCO — An investigational drug is safe and effective for patients with risk factors for influenza complications, results from the phase 3 CAPSTONE 2 study (NCT02949011) suggest.

For patients at high risk for complications, recovery was faster with baloxavir marboxil than with placebo, and the risk for complications was lower. The drug was well tolerated.

In addition, baloxavir marboxil — developed by Roche in partnership with Shionogi & Co. — was better than oseltamivir (Tamiflu, Roche) at shortening the duration of virus shedding and resolving influenza B illness. And it is administered in a single dose, unlike oseltamivir, which is administered twice a day for 5 days.

"This is the first phase 3 trial to demonstrate a significant, clinically meaningful benefit in people at high risk for complications from the flu for which there are no currently approved medicines," Sandra Horning, MD, chief medical officer and head of global product development for Roche, said in a company press release.

Last season, 900,000 people were hospitalized in the United States and 80,000 died from the flu, according to the Centers for Disease Control and Prevention (CDC) and the National Foundation for Infectious Diseases, as reported by Medscape Medical News.

And about 70% of hospitalizations and 90% of deaths last year were in people 65 years and older, according to the CDC.

High-Risk Patients

Results from the international, double-blind study were presented by Michael Ison, MD, from the Northwestern University Feinberg School of Medicine at in Chicago, during a late-breaker session here at IDWeek 2018.

In their study, Ison and his colleagues randomized one-third of patients to a single oral dose of baloxavir marboxil (40 or 80 mg, depending on body weight), one-third to oseltamivir 75 mg twice a day for 5 days, and one-third to placebo.

The primary end point was time to improvement of influenza symptoms.

Risk for influenza complications is elevated in people 65 years and older and in people with conditions such as asthma, chronic lung disease, diabetes, and heart disease.

Of the 1163 study patients with lab-confirmed influenza, 47.9% had the H3N2 subtype of the influenza A virus and 6.9% had the H1N1 subtype, and 41.6% had influenza B. The most common risk factors in this cohort were asthma and chronic lung disease (39.2%) and age of at least 65 years (27.4%).

Median time to improvement of influenza symptoms was about a day less with baloxavir marboxil than with placebo (73.2 vs 102.3 hours; <.0001), and time to improvement was numerically shorter than with oseltamivir (81.0 hours; = .8347).

Median time of viral shedding was shorter with baloxavir marboxil than with either oseltamivir or placebo (48 vs 96 vs 96 hours). The secondary end point of systemic antibiotic use was significantly lower with baloxavir marboxil than with placebo (3.4% vs 7.5%; = .0112), as was the rate of flu-related complications (2.8% vs 10.4%; < .0001).

This isn't a change-the-world drug.

Baloxavir marboxil is a one of a couple of drugs that experts in the field are watching because they could add an option to the influenza armamentarium, said Aaron Glatt, MD, from South Nassau Communities Hospital in Oceanside, New York.

"Right now, there are really limited options other than Tamiflu," he told Medscape Medical News. Oseltamivir is "not a great drug and doesn't work that well, but it's the only thing we have."

Baloxavir marboxil as "a little better" than oseltamivir, he said. "It is slightly more efficacious. It seems to be a bit faster in getting rid of the symptoms. It seems to be a little bit better in terms of decreasing the infectivity a little faster."

However, "this isn't a change-the-world drug," he added. It could potentially supplant oseltamivir, but much will depend on the cost.

"If you're going to have to pay significantly more to be symptom-free a day sooner, and people pay that out-of-pocket, the price may not be worth it," he pointed out. "For people who are very sick, the cost may not be appropriate to take into consideration; for others, cost will be a factor."

And it remains to be seen whether it will decrease mortality, he added.

Already Approved in Japan

Baloxavir marboxil is the first in a new class of antivirals designed to inhibit the cap-dependent endonuclease protein within the influenza virus, which is needed for replication, and is sold in Japan under the name Xofluza.

"If approved, baloxavir marboxil would be the first single-dose oral antiviral, and the first medicine with a novel proposed mechanism of action to treat the flu in nearly 20 years," according to Genentech. A decision on approval in the United States is expected by the end of the year.

Ison reports financial relationships with Romark, Janssen, Emergent BioScience, Shionogi, GlaxoSmithKline, VirBio, and Seqirus. Some of his coauthors are employees or have financial relationships with Shionogi & Co. Glatt has disclosed no relevant financial relationships.

IDWeek 2018: Abstract LB16. Presented October 6, 2018.

Follow Medscape on Twitter @Medscape and Marcia Frellick @mfrellick

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