Continuing to advance the science and address critical needs in flu This informational resource was developed as a reference guide for media only. Important Research Safety This resource details the clinical Home Program research program that has Information helped establish and expand the How Is indications for Xofluza® (baloxavir Flu and Xofluza marboxil), an FDA-approved COVID-19 antiviral medicine for use against Used? influenza (flu). Use the tabs on the side of each page, and the What Is Flu References links inside the text, for quick Xofluza? Basics and easy access to information on Xofluza and the flu. How Approval Xofluza Timeline May Work Media Inquiries: (650) 467-6800 M-US-00007626 (v1.0) > > Home What is What Is Xofluza? Xofluza? First and Only single-dose, How Is Xofluza is approved by the U.S. Food and Drug Administration (FDA) as a single-dose, oral 1,4-6 oral antiviral medicine to treat the flu Xofluza treatment for the flu (influenza) in people 12 years of age and older who have had flu symptoms Used? for no more than 48 hours and who are otherwise healthy or at high risk of developing flu-related First and Only antiviral complications. It is also approved for post-exposure prophylaxis of flu in patients 12 years of age and medicine indicated specifically for 1 patients at high risk of developing serious Approval older following contact with an individual who has the flu. 1,3-6 complications from the flu Timeline Key Phase III Study Results First single-dose antiviral medicine approved to help prevent flu in people who have been exposed to an individual Research who has the flu (known as post-exposure Program CAPSTONE-1 CAPSTONE-2 BLOCKSTONE prophylaxis)1,4-6 XOFLUZA PLACEBO XOFLUZA PLACEBO XOFLUZA PLACEBO 54 80 First FDA-approved medicine with a Flu 73 102 1% 13% novel proposed mechanism of action to Hours Hours Hours Hours Infected by Infected by Basics household member household member treat the flu in more than 20 years 1,4-6 Xofluza significantly reduced the Xofluza significantly reduced Xofluza showed a significant duration of flu symptoms compared to the time to improvement of flu prophylactic effect compared with placebo (median time 54 hours versus symptoms versus placebo in people placebo in people aged 12 years and First antiviral medicine designed to Flu and 80 hours; p<0.001) in patients aged age 12 years and older at high risk older following exposure to an infected inhibit the cap-dependent endonuclease 12 years and older. Similar efficacy of complications from flu (median household member. The proportion of protein within the flu virus, preventing COVID-19 results were seen between Xofluza time 73 hours versus 102 hours; household members who developed the formation of new viral particles by and oseltamivir in relation to duration p<0.001).1,10 flu was 1% in participants treated blocking viral replication early in the flu of symptoms (median time 54 hours with Xofluza and 13% in the placebo- lifecycle 7,8 How versus 54 hours).1,2 treated group, demonstrating a 90% reduction in risk.1,11 Xofluza First-in-Class medicine May Work The most frequently reported adverse events in adult and adolescent subjects with acute uncomplicated influenza with demonstrated antiviral activity receiving Xofluza were diarrhea (3%), bronchitis (3%), nausea (2%), sinusitis (2%), and headache (1%).1 against a wide range of flu viruses, including oseltamivir-resistant strains The most frequently reported adverse event (≥5%) in subjects receiving Xofluza for post-exposure prophylaxis of Important influenza was nasopharyngitis (6%).1 and avian strains (H7N9, H5N1) in non- Safety clinical studies 1,9,* Information *The relationship between antiviral activity in cell culture and clinical response to treatment in humans has not been established. M-US-00007626 (v1.0) > > References Home How is What Is Xofluza Used? Xofluza? Indications How Is Xofluza Xofluza is a prescription medicine used to treat influenza (flu) in people 12 years of age and Used? older who have had flu symptoms for no more than 48 hours and are otherwise healthy or The Centers for Disease Control and Prevention (CDC) defines at high risk of developing flu-related complications [see box at right]. It is also approved for people at high risk of serious flu post-exposure prophylaxis of flu in patients 12 years of age and older following contact with Approval complications as including those Timeline an individual who has the flu.1 who have conditions such as asthma, chronic lung disease, diabetes, heart Xofluza is contraindicated in patients with a history of hypersensitivity to baloxavir marboxil disease, and morbid obesity or adults 1 or any of its ingredients. 65 years of age or older. Access a full list Research at the web link above.3 Program Flu 1 Basics Dosing Based on results from clinical trials, ONLY ONE DOSE of Xofluza is needed to demonstrate benefit. Tablets: 20 mg and Body Weight (kg) Recommended Oral Dose Flu and 40 mg COVID-19 <176 lbs (80 kg) Two 20-mg tablets taken at the same time for a total single dose of 40 mg How Xofluza ≥176 lbs (80 kg) Two 40-mg tablets taken at the same time for a total dose of 80 mg May Work Important Safety Information M-US-00007626 (v1.0) > > References Home Approval What Is Timeline Xofluza? How Is Xofluza Used? October 2018 January 2019 October 2019 November 2020 Approval First New FDA- Available in Pharmacies Approved for High- Approved to Help Timeline Approved Flu Medicine Nationwide Risk Individuals Prevent Flu in in Nearly 20 Years Xofluza becomes available FDA expands the use Exposed Individuals FDA approves Xofluza for for patients across the U.S. of Xofluza to include Xofluza is approved Research the treatment of acute for the first time. people 12 years of age as a treatment to help uncomplicated flu in and older who have prevent flu in people 12 Program people 12 years of age been symptomatic for years of age and older and older who are no more than 48 hours who have been exposed otherwise healthy and and who are at high risk to flu (known as post- have been symptomatic for of developing flu-related exposure prophylaxis).1,11 Flu no more than 48 hours.2,13 complications.10,14 Basics Flu and COVID-19 2018 2019 2020 How Xofluza May Work Important Safety Information M-US-00007626 (v1.0) > > References Home Research Robust Clinical Evidence Demonstrates the Benefit of Xofluza in Different What Is Program Populations and Treatment Settings Xofluza? How Is Xofluza CAPSTONE-1 1,2 CAPSTONE-2 1,10 BLOCKSTONE 1,11 Used? Phase 1 2 3 Phase 1 2 3 Phase 1 2 3 Approval Completion: 2018 Completion: 2019 Completion: 2020 Timeline Design Design Design Multicenter, randomized, double-blind Multicenter, randomized, double-blind Multicenter, randomized, double-blind Research Xofluza vs placebo vs oseltamivir Xofluza vs placebo vs oseltamivir Xofluza vs placebo Program Patients (N=1436) Patients (N=2184) Patients (N=607) Ages 12–64 Ages 12+ Ages 12+ Flu Basics Otherwise healthy with acute At high risk of flu complications and Individuals who are either otherwise uncomplicated flu having acute uncomplicated flu healthy or at high risk of flu complications and are household Symptomatic for no more than 48 hours Symptomatic for no more than 48 hours contacts of patients with confirmed flu Flu and COVID-19 Primary Endpoint Primary Endpoint Primary Endpoint Duration of symptoms (time to Time to improvement of flu symptoms Proportion of participants testing alleviation of symptoms) compared with placebo positive for flu, with fever and one or compared with placebo more respiratory symptoms How Xofluza May Work Across all studies, Xofluza was administered as a one-time weight-based dose; when used as a comparator, oseltamivir was administered as weight-based doses twice daily for 5 days. Important Safety Information M-US-00007626 (v1.0) > > References Home Flu What Is Basics Xofluza? About Flu How Is Xofluza Flu is a highly contagious illness caused by flu viruses that infect the nose, throat and sometimes the lungs. While flu viruses can be Used? detected year-round in the U.S., they are most common during the fall and winter, with activity increasing in October and peaking between December and February. Some people are at higher risk for serious flu complications, including those who have conditions such as asthma, chronic lung disease, diabetes, heart disease and morbid obesity, and adults 65 years of age or older. For these Approval people, contracting the flu puts them at higher risk of hospitalization or even death.3,15,18 Timeline Flu Prevalence In The U.S. Research Each year, up to 45 million people will be affected by the flu. Since 2010, the Centers for Disease Control and Prevention (CDC) Program estimates that the flu has resulted annually in16,17 Flu Basics Flu and COVID-19 How 9.3M–45M 140K–810K 12K–61K Xofluza Illnesses Hospitalizations Deaths May Work Important Safety Information M-US-00007626 (v1.0) > > References Home Flu and Flu Prevention and Treatment During the What Is COVID-19 COVID-19 Pandemic Xofluza? The combination of a flu season and the global COVID-19 pandemic presents new challenges and unknowns. In addition to the added How Is urgency for people to get a flu vaccine, FDA-approved antiviral treatments are available for those who contract the flu.1,4-6,12,18 Xofluza Used? The CDC notes that flu and COVID-19 have overlapping signs and symptoms. During periods of community co-circulation of the two, the CDC cautions clinicians not to wait for the results of flu testing or SARS-CoV-2 testing before starting empiric antiviral treatment for flu in the following priority groups:12 Approval Timeline Research Program Flu Hospitalized Outpatients with Outpatients at higher risk for Basics patients with severe, complicated flu complications who present respiratory or progressive with any acute respiratory illness Flu and illness* respiratory illness* symptoms (with or without fever) COVID-19 How The CDC also noted that when influenza is known to be circulating in the community, clinicians can consider starting early ≤( 48 hours Xofluza after illness onset) empiric antiviral treatment of non-high-risk outpatients with suspected flu based upon clinical judgment, including May Work without an office visit.