Regulatory Decision Summary for Xofluza

Review decision

The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.

Product type:


Medicinal ingredient(s):

baloxavir marboxil

Therapeutic area:

Antivirals For Systemic Use

Type of submission:

New Drug Submission (New Active Substance)

Control number:

What was the purpose of this submission?


This New Drug Submission (NDS) - New Active Substance (NAS) was filed to obtain market authorization for Xofluza (baloxavir marboxil), an antiviral drug, for the treatment of uncomplicated influenza in patients aged 12 and above who have been symptomatic for no more than 48 hours and are otherwise healthy or are at high risk of developing influenza-related complications.

This NDS was filed simultaneously with Therapeutic Goods Administration of Australia (TGA), Health Canada (HC), and Swiss Medic via the Australia, Canada, Switzerland, and Singapore (ACSS) Consortiums New Chemical Entities Work Sharing Initiative (NCEWSI). The review was jointly conducted.


Why was the decision issued?


Xofluza (baloxavir marboxil) is a new class of anti-influenza virus drug with a novel mechanism of action. Baloxavir, the active form, selectively inhibits cap-dependent endonuclease activity necessary for replication of influenza viruses.

The otherwise healthy (OwH) (T0831) and high risk (HR) (T0832) Phase 3 pivotal studies supporting market authorization of Xofluza were randomized, double-blind, multicentre, international, placebo- and active-controlled studies designed to evaluate the efficacy and safety of a single oral dose of Xofluza [40 milligrams (mg) or 80 mg, depending on body weight] in patients with uncomplicated influenza weighing at least 40 kilograms (kg). Study T0831 included OwH patients 12 to 64 years of age with no significant comorbidities, while Study T0832 included patients 12 years of age and older (no upper age limit) at high risk of developing influenza-related complications. The supportive OwH Phase 2 T0821 study was a multicentre, randomized, double-blind, parallel-group, placebo-controlled study conducted in Japan, designed to evaluate the efficacy and safety of a single dose of Xofluza (10 mg, 20 mg, or 40 mg irrespective of body weight) in OwH adults (20 to 64 years of age) with uncomplicated influenza. In all three studies, Xofluza was administered within 48 hours of the onset of symptoms and without regard to meals. The primary endpoints were the time to alleviation of influenza symptoms (T0831 and T0821) and the time to improvement of influenza symptoms (T0832).

The Phase 3 pivotal studies met their primary endpoints, with Xofluza treatment providing statistically significant reductions in median time to alleviation (26.5 hours; T0831) and median time to improvement (29.1 hours, T0832) of influenza symptoms over placebo. In T0832, a reduction in the overall incidence of influenza-related complications, a secondary endpoint, was observed with Xofluza (3%) compared with placebo (10%); however, the result was mainly driven by lower incidences of bronchitis and sinusitis, and there were no significant treatment differences for death, hospitalization, otitis media and pneumonia. The Phase 2 study (T0821) was supportive of the OwH pivotal study; at 40 mg, the median time to alleviation of symptoms was 49.5 hours with Xofluza versus 77.7 hours with placebo.

Overall, Xofluza was well tolerated and no apparent safety concerns were identified in the OwH or HR studies. Based on a review of post-marketing data, Xofluza is likely to be causally associated with hypersensitivity reactions characterized by urticaria, angioedema and anaphylaxis/anaphylactic reaction. A safety signal identified during the review period related to prescribing and dispensing errors associated with different dose packs leading to medication errors, including overdosage and underdosage of Xofluza, led to risk mitigation via a clear description of dosing instructions and available packaging configurations throughout product labelling.

A Risk Management Plan (RMP) for Xofluza was submitted by Hoffman-La Roche Limited to Health Canada. Upon review, the RMP was considered to be acceptable. The RMP is designed to describe known and potential safety issues, to present the monitoring scheme and when needed, to describe measures that will put in place to minimise risks associated with the product.

Health Canada recommends issuance of marketing authorization for Xofluza for the treatment of uncomplicated influenza in patients 12 years of age and older who have been symptomatic for no more than 48 hours and who are otherwise healthy or at high risk of developing influenza complications.


Decision issued

Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.