FDA Accepts Genentech's New Drug Application for Xofluza for the Treatment of Influenza in Children

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 New Drug Application (NDA) as well as two supplemental New Drug Applications (sNDA) for Xofluza^® (baloxavir marboxil). The FDA accepted a NDA for a new formulation of Xofluza as one-dose granules for oral suspension (2 mg/mL), potentially offering a more convenient option for children and those who have difficulty swallowing. In addition, the application seeks approval of Xofluza for the treatment of acute uncomplicated influenza in otherwise healthy children aged one to less than 12 years of age who have been symptomatic for no more than 48 hours. The FDA also accepted an sNDA for post-exposure prophylaxis of influenza in people one year of age and older for both the oral suspension and currently-available tablet formulation. The FDA is expected to make a decision on these approvals by November 23, 2020.

"As this has been one of the hardest-hitting influenza seasons for children in the past decade, there is a critical need for additional treatment options that attack influenza in different ways. Today's milestone brings us closer to providing single-dose Xofluza to children with influenza," said Levi Garraway, M.D., Ph.D., chief medical officer and head of Global Product Development. "We also look forward to working with the FDA to incorporate Xofluza as a preventive treatment following exposure to influenza."

The proposed additional formulation of Xofluza involves granules that are reconstituted with water to form an oral suspension by a pharmacist prior to dispensing to an individual. If approved, this Xofluza oral suspension would be administered as a one-time dose and would be available for children aged one to less than 12 years of age and those who have difficulty swallowing. Xofluza tablets are currently approved in many countries around the world for the treatment of influenza types A and B.

The filings are based on positive results from two Phase III studies, miniSTONE-2 and BLOCKSTONE, which were both recently presented as late breakers at the 2019 OPTIONS X congress in Singapore. The miniSTONE-2 study evaluated the safety, pharmacokinetics and efficacy of single-dose, oral suspension Xofluza compared with oseltamivir in otherwise healthy children aged one to less than 12 years of age with influenza. BLOCKSTONE evaluated Xofluza compared with placebo as a preventive treatment for household members (adults and children) who were living with someone with influenza.

Xofluza is FDA-approved to treat influenza in people 12 years of age and older who have had influenza symptoms for no more than 48 hours and who are otherwise healthy or at high risk of developing influenza-related complications. Although some of the symptoms of COVID-19 and influenza can look similar, the two illnesses are caused by completely different viruses. Xofluza is specifically designed to treat influenza viruses only and has not been proven to be effective to treat human coronaviruses such as COVID-19.

About miniSTONE-2

miniSTONE-2 is a Phase III, randomized, double-blind study that evaluated the safety, pharmacokinetics and efficacy of a single dose of Xofluza compared with oseltamivir in otherwise healthy children aged one to less than 12 years with an influenza infection and displaying influenza symptoms for no more than 48 hours (temperature of 38°C or over, and one or more respiratory symptoms).

Participants enrolled in the study were recruited in parallel into two cohorts: children aged five to less than 12 years and children aged one to less than five years. Participants in both cohorts were randomly assigned to receive a single dose of Xofluza or oseltamivir twice a day over five days (dosing according to body weight). Time to alleviation of influenza signs and symptoms were comparable between Xofluza and oseltamivir. The median time to alleviation of signs and symptoms in influenza-infected participants was 138 hours (95% CI: 117, 163) and 150 hours (95% CI: 115, 166) for those who received Xofluza or oseltamivir, respectively. Xofluza was well tolerated, with no new safety signals identified.

About BLOCKSTONE

BLOCKSTONE is a Phase III, double-blind, multicenter, randomized, placebo-controlled, post-exposure prophylaxis study that evaluated a single dose of Xofluza compared with placebo in household members (adults and children) in Japan who were living with someone with an influenza infection confirmed by a rapid influenza diagnostic test (the ?index patient').

Participants enrolled in the study were household members of someone who had been diagnosed with influenza. The participants were randomized to receive a single dose of Xofluza (dose according to body weight) or placebo as a preventive measure against developing influenza.

Xofluza showed a significant prophylactic effect on influenza infection after a single oral dose in people exposed to an infected family member. The proportion of household members who became symptomatically ill following infection with influenza was significantly lower in those treated preventively with Xofluza compared to those treated with placebo (proportion of subjects with influenza virus infection, fever and other influenza symptoms in the 10-day observation period: 2% versus 14%). Xofluza was well tolerated in this study and no new adverse drug reactions were identified.

About Xofluza^® (baloxavir marboxil)

Xofluza is a first-in-class, one-dose oral medicine with an innovative 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. Xofluza is the first in a class of antivirals designed to inhibit the cap-dependent endonuclease protein, which is essential for viral replication.

In October 2018, Xofluza was first approved by the FDA for the treatment of acute, uncomplicated influenza in otherwise healthy people 12 years of age and older who have been symptomatic for no more than 48 hours, representing the first new antiviral to treat influenza in the U.S. in 20 years. In October 2019, Xofluza became the only antiviral medicine approved by the FDA to specifically treat patients at high risk of developing serious complications from influenza.

Xofluza is being further studied in a Phase III development program, including children under the age of one (NCT03653364), severely ill, hospitalized people with influenza (NCT03684044), as well as to assess the potential to reduce transmission of influenza from an infected person to healthy people (NCT03969212).

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 and who are otherwise healthy or at high risk of developing flu-related complications.

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).

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.

If you take too much Xofluza, go to the nearest emergency room right away.

Xofluza may cause serious side effects, including allergic reactions.

Get emergency medical help right away if you develop any of these signs and symptoms of an allergic reaction:

• trouble breathing
• skin rash, hives or blisters
• swelling of your face, throat or mouth
• dizziness or lightheadedness

The most common side effects are diarrhea, bronchitis, sinusitis, headache, and nausea.

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 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 is one of the most common, yet serious, infectious diseases, representing a significant threat to public health. Since 2010, the Centers for Disease Control and Prevention (CDC) estimates that influenza has resulted annually in 9.3 to 45 million illnesses, 140,000 to 810,000 hospitalizations and 12,000 to 61,000 deaths. Although vaccines are an important first line of defense in preventing influenza, there is a need for new medical options for prophylaxis and treatment. Other antiviral medicines have limitations with respect to efficacy, convenience of dosing and resistance. 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.