FDA Accepts Genentech’s Supplemental New Drug Application for XOFLUZA (baloxavir marboxil) for the Treatment of Influenza in People at High Risk of Complications

March 6, 2019 |

8 min read

XOFLUZA would be the first antiviral medicine approved specifically for the high-risk population

March 6, 2019 06:00 UTC

– XOFLUZA would be the first antiviral medicine approved specifically for the high-risk population –

SOUTH SAN FRANCISCO, Calif.--(BUSINESS WIRE)-- Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), today announced that the U.S. Food and Drug Administration (FDA) has accepted a supplemental New Drug Application (sNDA) for XOFLUZA™ (baloxavir marboxil) as a single-dose, oral treatment for people at high risk of complications from the flu. The Centers for Disease Control and Prevention (CDC) defines people at high risk for serious flu complications to include adults 65 years of age or older, or those who have conditions such as asthma, chronic lung disease, morbid obesity or heart disease. The FDA is expected to make a decision on approval by November 4, 2019.

“Influenza, or ‘flu,’ can be especially debilitating for people considered to be high risk, as they have an increased likelihood of serious complications, worsening of existing health problems and even hospitalization or death,” said Sandra Horning, M.D., chief medical officer and head of Global Product Development. “XOFLUZA is the first antiviral medicine to demonstrate a significant and clinically meaningful benefit in people at high risk of complications from the flu, for which there are currently no approved medicines.”

The sNDA is based on results from the Phase III CAPSTONE-2 study of a single dose of XOFLUZA compared with placebo or oseltamivir 75 mg, twice daily for five days, in people 12 years of age or older who are at high risk of complications from the flu.

The FDA approved XOFLUZA in October 2018 for the treatment of acute, uncomplicated influenza in people 12 years of age or older. It is the first and only single-dose oral medicine approved to treat the flu, and the first new flu medicine with a novel proposed mechanism of action in nearly 20 years.

About CAPSTONE-2

CAPSTONE-2 is a Phase III multicenter, randomized, double-blind study that evaluated the efficacy and safety of a single dose of XOFLUZA compared with placebo and oseltamivir in 2,184 people 12 years of age or older who are at high risk of complications from the flu. The primary objective of the study evaluated the efficacy of a single dose of XOFLUZA compared with placebo by measuring the time to improvement of influenza symptoms. Important secondary endpoints compared outcomes in XOFLUZA versus placebo or oseltamivir, including time to resolution of fever, time to cessation of viral shedding, infectious virus detection in swabs of the nose and throat, prescription of antibiotics and influenza-related complications. The study, which was first presented in October 2018 at IDWeek, found that XOFLUZA:

Significantly reduced the time to improvement of influenza symptoms versus placebo in people at high risk of complications from influenza (median time 73.2 hours versus 102.3 hours; p<0.0001);
Demonstrated superior efficacy (reduced time to improvement of influenza symptoms) versus placebo and oseltamivir in influenza type B (median time of 74.6 hours versus 100.6 hours and 101.6 hours, respectively (p=0.0138, p=0.0251);
Demonstrated efficacy for secondary endpoints compared to placebo:
- Significantly reduced the time to resolution of fever (median time of 30.8 hours versus 50.7 hours; p<0.0001), the incidence of influenza-related complications (2.8 percent versus 10.4 percent; p<0.05), the use of systemic antibiotics (3.4 percent versus 7.5 percent; p=0.01) and the length of time the virus continued to be released from the body (viral shedding; median time of 48 hours versus 96 hours; p<0.0001).
Similar efficacy results were seen between XOFLUZA and oseltamivir for several secondary endpoints, but a significant difference was observed in the time to cessation of viral shedding favoring XOFLUZA:
- No significant reduction in the time to resolution of fever (median time of 30.8 hours for XOFLUZA versus 34.3 hours for oseltamivir; p<0.2425), the incidence of influenza-related complications (2.8 percent for XOFLUZA versus 4.6 percent for oseltamivir; p=0.2558) and the use of systemic antibiotics (3.4 percent for XOFLUZA versus 3.9 percent for oseltamivir; p=0.8478).
- Significantly reduced the length of time the virus continued to be released from the body (viral shedding; median time of 48 hours versus 96 hours; p<0.0001).

In CAPSTONE-2, XOFLUZA was well tolerated, with no safety signals identified. XOFLUZA had a numerically lower overall incidence of reported adverse events (25.1 percent) compared with placebo (29.7 percent) or oseltamivir (28.0 percent). The most common adverse events reported in the XOFLUZA group were bronchitis (2.9 percent), diarrhea (2.7 percent), nausea (2.7 percent) and sinusitis (1.9 percent). The study was conducted globally by Shionogi & Co., Ltd.

About XOFLUZA™ (baloxavir marboxil)

XOFLUZA is a first-in-class, single-dose oral medicine with a novel proposed mechanism of action that has demonstrated efficacy in a wide range of influenza viruses, including in vitro activity against oseltamivir-resistant strains and avian strains (H7N9, H5N1) in non-clinical studies. Unlike other currently available antiviral treatments, XOFLUZA is the first in a new class of antivirals designed to inhibit polymerase acidic endonuclease, an enzyme essential for viral replication.

XOFLUZA will be further studied in a Phase III development program including pediatric populations, post-exposure prophylaxis and severely ill hospitalized people with influenza, as well as to assess the potential to reduce transmission in otherwise healthy people.

XOFLUZA was discovered by Shionogi & Co., Ltd. and is being further developed and commercialized globally in collaboration with the Roche Group (which includes Genentech in the U.S.) and Shionogi & Co., Ltd. Under the terms of this agreement, Roche holds worldwide rights to XOFLUZA excluding Japan and Taiwan, which will be retained exclusively by Shionogi & Co., Ltd.

XOFLUZA U.S. Indication

XOFLUZA is a prescription medicine used to treat the flu (influenza) in people 12 years of age and older who have had flu symptoms for no more than 48 hours.

It is not known if XOFLUZA is safe and effective in children younger than 12 years of age or weighing less than 88 pounds (40 kg).

Limitations of Use: Influenza viruses change over time, and factors such as the virus type or subtype, emergence of resistance or changes in viral virulence could diminish the clinical benefit of antiviral drugs. Consider available information on drug susceptibility patterns for circulating influenza virus strains when deciding whether to use XOFLUZA.

Important Safety Information

Do not take XOFLUZA if you are allergic to baloxavir marboxil or any of the ingredients in XOFLUZA.

Before you take XOFLUZA, tell your healthcare provider about all of your medical conditions, including if you:

are pregnant or plan to become pregnant. It is not known if XOFLUZA can harm your unborn baby.
are breastfeeding or plan to breastfeed. It is not known if XOFLUZA passes into your breast milk.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins and herbal supplements.

Talk to your healthcare provider before you receive a live flu vaccine after taking XOFLUZA.

Take XOFLUZA with or without food. Do not take XOFLUZA with dairy products, calcium-fortified beverages, laxatives, antacids or oral supplements containing iron, zinc, selenium, calcium or magnesium.

The most common side effects are diarrhea, bronchitis, nausea, common cold symptoms (nasopharyngitis) and headache.

XOFLUZA is not effective in treating infections other than influenza. Other kinds of infections can have symptoms like those of the flu or occur along with the flu and may need different kinds of treatment. Tell your healthcare provider if you feel worse or develop new symptoms during or after treatment with XOFLUZA or if your flu symptoms do not start to get better.

Please see the XOFLUZA full Prescribing Information for complete safety information.

You are encouraged to report side effects to Genentech by calling 1-888-835-2555 or to the FDA by visiting http://www.fda.gov/medwatch or calling 1-800-FDA-1088.

About Genentech in influenza

Influenza, or flu, is one of the most common yet serious infectious diseases. Since 2010, the CDC estimates that the flu has resulted annually in 9.3 to 49 million illnesses, 140,000 to 960,000 hospitalizations and 12,000 to 79,000 deaths. Although vaccines are an important first line of defense in preventing the flu, there is a need for new medical options for prophylaxis and treatment. Current treatments – including existing vaccines and antiviral drugs – have limitations as flu viruses are constantly changing and new antiviral medicines are necessary. Genentech is committed to addressing the unmet need in this area through its agreement with Shionogi & Co., Ltd. to develop and commercialize XOFLUZA.

About Genentech

Founded more than 40 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.