HONG KONG – Osaka, Japan-based Shionogi & Co Ltd. continues to make global inroads with its influenza treatment, Xofluza (baloxavir marboxil), submitting supplemental new drug applications in Japan and Taiwan for a post-exposure prophylaxis indication on the back of positive results from its phase III trials.

A company source told BioWorld the company expects “further ex-Japan approvals in 2020. Shionogi has submitted an application in Europe to treat otherwise healthy and high-risk patients with influenza under the post-exposure prophylaxis indication, with approval expected around the first quarter of 2021.”

The company published the results from the drug’s BLOCKSTONE study in The New England Journal of Medicine earlier this month. The phase III, multicenter, double-blind and placebo-controlled study took place in Japan during the 2018/19 flu season to test the efficacy of Xofluza in preventing confirmed influenza patients’ household members from contracting the virus over a 10-day observation period.

The study successfully met its primary endpoint, which was the proportion of participants who contracted the influenza virus and exhibited at least one respiratory symptom as well as a fever, after taking Xofluza and being in contact with an infected household member.

The source said the study’s “primary endpoints were achieved, and positive results were also obtained for the secondary endpoints.” The results showed that 1.9% of the 374 participants who took Xofluza developed clinical influenza, compared to 13.6% of the 375 patients who received a placebo, which demonstrates an 86% reduction in risk.

Also, 5.3% of the participants who took Xofluza were infected with the influenza virus and showed fever or one or more respiratory symptoms, compared to 22.4% in the placebo-treated group. Xofluza reduced the risk of participants developing influenza illness by 76% compared to placebo. Shionogi said the incidence of adverse events was 22.2% and 20.5% for Xofluza and placebo groups, respectively, with no serious adverse events reported for Xofluza.

The BLOCKSTONE results came on the back of positive results from a global phase III CAPSTONE-13 study in healthy patients 12 and older, the CAPSTONE-24 study in patients 12 and older with a high risk of influenza-related complications, and the CAPSTONE-2 study.

“The BLOCKSTONE study demonstrated that baloxavir marboxil [Xofluza] strongly prevents influenza infection in the household setting, which plays a major role in influenza epidemics,” said Hideyuki Ikematsu, president of Ricerca Clinica Co., who also served as research director of the influenza study group of the Japan Physicians Association and lead author of the published paper. “The strong antiviral activity of baloxavir marboxil resulted in the prevention of influenza infection and the suppression of the onset of influenza symptoms.

“I believe that baloxavir marboxil is a promising option for the prophylaxis and prevention of influenza for persons at high-risk of influenza complications and health care professionals who are at the front lines and must be protected during influenza epidemics,” Ikematsu added.

Xofluza is a single, oral dose treatment for influenza discovered and developed in-house by Shionogi. It is designed to inhibit the cap-dependent endonuclease in the polymerase acidic protein, the enzyme critical for viral replication. It has demonstrated an antiviral effect across a range of influenza viruses, including oseltamivir-resistant strains and avian strains such as H7N9 and H5N1, in nonclinical studies.

The drug is currently approved for use in the U.S. and Japan as well as 19 other countries. In October 2018, the FDA approved Xofluza as a treatment for acute, uncomplicated influenza in patients 12 and older who have been symptomatic for no more than 48 hours.

The FDA also accepted a new drug application in March for Xofluza in single-dose granules for an oral suspension format, making the drug easier to take for children and patients who have difficulty swallowing. The same application sought approval for the drug to treat acute, uncomplicated influenza in otherwise healthy children between the ages of younger than 1 to younger than 12 who have been symptomatic for no more than 48 hours.

A University of Texas study published in the Nature Communications in June examining Xofluza and Tamiflu (oseltamivir, Roche Holding AG) concluded that the two are among some antivirals that are useful for more than helping patients recover. The antivirals could also prevent more cases and deaths if used in the early stages of infection.

The study also concluded that Xofluza, the newer treatment, was able to stop virus replication effectively and rapidly, thus decreasing patients’ contagious period and limiting the spread of influenza. “The development of antivirals against the COVID-19 virus that function like Xofluza might similarly curtail transmission and save lives,” the study said.

The company also submitted a supplemental new drug application for the post-exposure prophylaxis of influenza in people 1 and older for both the oral suspension and currently available tablet formats. The company expects the FDA’s decision by Nov. 23.

Although discovered and developed by Shionogi, the Japanese company inked an agreement to further develop and commercialize Xofluza, then known as S-033188, with Switzerland’s Roche Holding AG in February 2016. Under the agreement, Roche gained the worldwide rights to the drug, with Shionogi retaining the rights to the drug in Japan and Taiwan.

Shionogi said Roche had previously presented the results from the MINISTONE-2 global phase III study assessing Xofluza in otherwise healthy children, ages 1 to under 12.

Roche is currently conducting “a phase III development program including children under the age of 1, and severely ill, hospitalized patients, as well as to assess the potential to reduce transmission of influenza from an infected person to healthy people,” the source said.

Shionogi has previously been focused on treatments for psychiatric and neurological diseases; however, the firm is currently looking to develop treatments in areas outside beyond those, though the source declined to provide more specifics about the company’s newer endeavors.

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