乌鸦传媒

SAN DIEGO -- An investigational anti-influenza drug outperformed a standard medication on some virologic endpoints, a researcher said.

In a Phase III trial, the new drug, a cap-dependent endonuclease inhibitor, was quicker than oseltamivir (Tamiflu) in reducing virus levels in patients and cutting viral shedding, according to Simon Portsmouth, MD, of Shionogi in Florham Park, New Jersey. The company is developing the drug.

But there was little difference in how quickly the two drugs alleviated the symptoms of the flu, Portsmouth said at a late-breaker session at the annual IDWeek meeting, sponsored jointly by the (IDSA), the (PIDS), the (SHEA), and the (HIVMA).

On the other hand, the drug -- known in the trial as S-033188, but recently named baloxavir marboxil -- outperformed placebo on all counts in the CAPSTONE-1 trial, Portsmouth said.

The virologic endpoints are interesting, but the bottom line is that people want to feel well more quickly, commented Natasha Chida, MD, of Johns Hopkins University School of Medicine in Baltimore, co-moderator of the IDWeek session.

Clearing the symptoms is important, "in terms of work force issues and the cost to society of having people off work," she told 乌鸦传媒.

"It didn't seem that drug was much better than oseltamivir," she added, but investigating ways to get people back to work sooner is "very helpful."

The trial, conducted in Japan, was partly placebo-controlled because of concerns in that country that oseltamivir might be dangerous for young people, Portsmouth said. The trial was stratified into two age groups: ages 12-18 years (children and teens) and ages 19-64 years.

In the younger group, participants were randomly assigned to a single shot of one of two doses of the drug (based on weight) or to placebo. The older participants were assigned on a 2:2:1 basis to get one shot of S-033188, oseltamivir, or placebo, with dosing of S-033188 again based on weight.

Eligible patients had to be otherwise healthy, have uncomplicated symptomatic flu -- defined as an axillary temperature of at least 38°C, and at least one respiratory and one systemic symptom -- and be no more than 48 hours from onset of symptoms.

A separate trial is under way testing the drug in patients with high-risk flu, Portsmouth said.

The primary endpoint was the time to alleviation of symptoms (TTAS), defined as the time from start of therapy to the point where all the symptoms of flu -- cough, sore throat, headache, nasal congestion, fever or chills, muscle or joint pain, and fatigue -- were either mild or non-existent.

Secondary endpoints included that change from baseline in virus titers, the time to the cessation of viral shedding, the time to resolution of fever, and the time to return to pre-flu health.

Portsmouth said the drug significantly reduced TTAS by 26.5 hours, compared with placebo, and also did better on all the secondary endpoints.

Against oseltamivir, TTAS was "identical" but S-033188 did better on other endpoints:

• The time to cessation of fever was 24 hours for S-033188 but 72 hours for oseltamivir.
• The reduction in viral titers was about a 4.5 log drop in the first day for S-033188 but 2.5 logs for oseltamivir.
• Also on the first day, 46% of those getting the new drug remained positive for influenza, compared with 90% of those on oseltamivir.

"The clinical findings are similar," Portsmouth said, "but clearly the virology is much better."

The drug was generally well tolerated, with numerically fewer adverse events than either placebo or oseltamivir, he added.

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