Study Shows Baloxavir Marboxil May Prevent Influenza Infection

Baloxavir marboxil (Xofluza, Genentech) is a first in class antiviral flu treatment indicated in the United States for patients age 12 years and older who have been symptomatic for no more than 48 hours.¹ The recently released Blockstone study showed that baloxavir marboxil was effective as post-exposure prophylaxis against influenza.² 

This phase 3 study revealed that patients exposed to a household member with influenza and were treated preventatively with baloxavir marboxil were significantly less likely to develop the flu compared with those treated with placebo (1.9% vs. 13.6%, P < 0.0001). The primary endpoint was the proportion of patients who tested positive for the flu and had fever, and at least 1 respiratory symptom between days 1 and 10. This is the first study to show that a single treatment with baloxavir marboxil was effective as post-exposure prophylaxis.² 

Study researchers evaluated a single dose of baloxavir marboxil compared with placebo in adult and children household members in Japan living with someone infected with influenza, confirmed by a rapid influenza diagnostic test during the 2018-2019 flu season.² Patients were randomly assigned to receive a single dose of baloxavir marboxil or placebo, and there was a 10 day observation period. No serious adverse events were reported with baloxavir marboxil during the study.² 

Strengths of the study include that it was placebo-controlled, and the dosing was weight based from the manufacturer prescribing information. The study duration of 10 days was short to assess adverse effects. Future research should include longer study duration.  Important questions to be raised in future studies include the number of patients that were evaluated during this study and how many received the influenza vaccine.  

Roche, the parent company of Genentech, is planning to submit these study results to the FDA for a new possible indication for its baloxavir marboxil product.³ Also, a supplemental New Drug Application was submitted to the FDA for individuals at high risk of flu complications, such as adults age 65 years and older and those with certain chronic health conditions, with an expected decision by November 2019.^2,3 

Since baloxavir marboxil’s approval, sales in the United States have not been promising,3 and the drug is approved in Japan for the treatment of influenza in children and adults. There is some concern about baloxavir marboxil resistance, which could result in a lack of efficacy against mutant flu strains.

Baloxavir marboxil dosing is weight based and patients 40 kg to less than 80 kg should receive a single oral dose of 40 mg.1 Patients weighing at least 80 kg should receive a single oral dose of 80 mg.¹ Studies have demonstrated that this treatment alleviated flu symptoms in a shorter time frame than placebo. However, evidence suggests that 1 dose of baloxavir marboxil has a similar efficacy to 5 days of oseltamivir phosphate (Tamiflu, Genentech) treatment.⁴ Genentech's baloxavir marboxil is a 1-dose medication, which may improve patient compliance.

The most common adverse events associated with baloxavir marboxil include diarrhea, bronchitis, nasopharyngitis, headache, and nausea. Counseling points include avoiding dairy or products that contain calcium, aluminum, or iron at the time of the drug's administration, as these may decrease the efficacy of baloxavir marboxil. Pharmacists should educate patients to always get their annual influenza vaccine, as this is the best way to prevent the flu.

References

• Xofluza [prescribing information].  San Francisco, CA; Genentech USA, Inc.; 2018. https://www.gene.com/download/pdf/xofluza_prescribing.pdf. Accessed June 17, 2019.
• Phase III study showed Xofluza (baloxavir marboxil) is effective at preventing influenza infection [news release]. San Francisco, CA; June 3, 2019: Genentech website.  https://www.gene.com/media/press-releases/14793/2019-06-03/phase-iii-study-showed-xofluza-baloxavir. Accessed June 17, 2019.
• Blankenship K. Roche’s Xofluza scores trial win in flu prevention, providing sales hope as Tamiflu craters. FiercePharma.  https://www.fiercepharma.com/pharma/roche-s-xofluza-scores-trial-win-flu-prevention-providing-sales-hope-as-tamiflu-craters. Published June 5, 2019. Accessed June 17, 2019.
• Hayden FG, Sugaya N, Hirotsu N, et al. Baloxavir marboxil for uncomplicated influenza in adults and adolescents. N Engl J Med.  2018; 379(10):913-923. doi: 10.1056/NEJMoa1716197.