Roche Announces Phase III BLOCKSTONE Trial Results: Xofluza Reduces Post-Exposure Influenza Infection Risk by 86%

On September 1, at the OPTIONS X 2019 conference held in Singapore, Roche Group promptly presented positive data from two Phase III clinical trials of its investigational influenza drug Xofluza (baloxavir marboxil). Roche is leading the global frontline against influenza—join us as we explore the details!

The BLOCKSTONE study met its primary endpoint: compared with the placebo group, fewer participants in the Xofluza group tested positive for influenza or developed fever or at least one respiratory symptom.

Xofluza is poised to become a convenient and effective treatment option, whether for reducing ordinary seasonal influenza or for limiting large-scale flu outbreaks.

The Phase III BLOCKSTONE study demonstrated that post-exposure prophylaxis with Xofluza in household contacts of influenza-infected individuals significantly reduced the risk of developing influenza by 86% compared with placebo. Study results showed that only 1.9% of household members treated with Xofluza developed influenza, versus 13.6% in the placebo group (p<0.0001). Moreover, Xofluza demonstrated statistically significant benefits over placebo across different subtypes of influenza A (H1N1: 1.1% vs. 10.6%, p=0.0023; H3: 2.8% vs. 17.5%, p<0.0001). Furthermore, this difference was also observed among populations at high risk for influenza infection (2.2% vs. 15.4%, p=0.0435) and in children under 12 years of age, who are more susceptible to influenza (4.2% vs. 15.5%, p=0.0339). Xofluza exhibited a safety profile comparable to that of placebo, with overall adverse event rates of 22.2% for Xofluza and 20.5% for placebo.No serious adverse events were reported.

Dr. Sandra Horning, Roche’s Chief Medical Officer and Global Head of Product Development, stated:

Influenza viruses can rapidly infect those around us; therefore, limiting transmission within households may prevent severe impacts on the broader population, representing a critical step in the global fight against influenza. We are encouraged by the results of the BLOCKSTONE study, which demonstrate for the first time the efficacy of Xofluza for post-exposure prophylaxis of influenza, and we look forward to sharing these data with health authorities.

The BLOCKSTONE study also demonstrated that, even with less stringent eligibility criteria (with some participants presenting with influenza, fever, or one or more respiratory symptoms), post-exposure prophylaxis with Xofluza significantly reduced the risk of influenza among household contacts by 76% compared with placebo (5.3% vs. 22.4%; p<0.0001).

Phase III MINISTONE-2 data showed that the safety profile of Xofluza in children was consistent with its known safety profile, and its efficacy was comparable to that of oseltamivir.

As a new single-dose oral suspension, Xofluza is a potentially more convenient treatment option for children.

Children are at high risk of influenza, with flu-related complications leading to nearly 1 million hospitalizations annually among children under five years old worldwide.

The Phase III MINISTONE-2 study demonstrated that a single dose of Xofluza is a well-tolerated and effective potential treatment for influenza in previously healthy children under 12 years of age. The study evaluated the proportion of patients experiencing adverse events (AEs) or serious adverse events by Day 29, showing consistency with the known safety profile of Xofluza and meeting the primary endpoint. Among participants treated with Xofluza, 46.1% experienced at least one treatment-emergent adverse event, compared with 53.4% in the oseltamivir group. The study also indicated that the efficacy of Xofluza was comparable to that of oseltamivir, an established effective treatment for pediatric influenza. Furthermore, consistent with data from adult and adolescent populations, Xofluza reduced the duration of influenza viral shedding by more than two days compared with oseltamivir (median time to cessation of viral shedding: 24.2 hours vs. 75.8 hours).

Dr. Sandra Horning, Roche’s Chief Medical Officer and Head of Global Product Development, stated:

Each year, approximately one in three children contracts influenza. Their immature immune systems result in a slower response to infection and a higher susceptibility to complications. We are committed to developing more convenient new treatment regimens for pediatric influenza patients and look forward to sharing these data with global health organizations.

MINISTONE-2 is the first global Phase III study of Xofluza in children. It demonstrated that Xofluza was comparable to oseltamivir with respect to key secondary endpoints, including time to alleviation of influenza symptoms and signs (median 138.1 hours vs. 150.0 hours).

MINISTONE-2 is the fourth Phase III study of Xofluza to report positive results, confirming its benefits across multiple populations (previously healthy individuals, high-risk groups, and children) and treatment settings (symptomatic cases and post-exposure prophylaxis). Xofluza is undergoing further investigation in a Phase III development program that includes infants under one year of age and hospitalized patients with severe influenza, and will assess the potential of Xofluza to reduce the transmission of influenza from infected individuals to healthy contacts.

References

[1] Ikematsu H, et al. Single-dose baloxavir for the prevention of influenza among household contacts: a randomized, double-blinded, placebo controlled post-exposure prophylaxis study (BLOCKSTONE). OPTIONS X 2019; 2019 Aug 28-Sept 1; Singapore. Abstract #11718.

[2] Hayden F, et al.  Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents. N Engl J Med 2018; 379:913-923.

[3] Ison M, et al. CAPSTONE-2 trial. Infectious Disease Week; 2018 Oct 3-7; San Francisco. CA, USA. Abstract #LB16. [Internet; cited 2019 August]. Available from: https://idsa.confex.com/idsa/2018/webprogram/Paper74204.html.

[4] Baker J, et al. Single-dose baloxavir marboxil for the treatment of influenza in otherwise-healthy children aged 1 to <12 years (miniSTONE-2). OPTIONS X 2019; 2019 Aug 28-Sept 1; Singapore. Abstract #11756.

[5] Baker J, et al. Single-dose baloxavir marboxil for the treatment of influenza in otherwise-healthy children aged 1 to <12 years (miniSTONE-2). Presented at: OPTIONS X; 2019 August 28-September 1; Singapore. Abstract #11756.

[6] Hayden F, et al.  Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents. N Engl J Med 2018;379:913-923.

[7] Ison M, et al. CAPSTONE-2 trial. Infectious Disease Week; 2018 Oct 3-7; San Francisco. CA, USA. Abstract #LB16. [Internet; cited 2019 August]. Available from: https://idsa.confex.com/idsa/2018/webprogram/Paper74204.html.

[8] Ikematsu H, et al. Single-dose baloxavir for the prevention of influenza among household contacts: a randomized, double-blinded, placebo controlled post-exposure prophylaxis study (BLOCKSTONE). OPTIONS X 2019; 2019 Aug 28-Sept 1; Singapore. Abstract #11718.

[9] ClinicalTrials.gov. Study to Assess the Safety, Pharmacokinetics, and Efficacy of Baloxavir Marboxil in Healthy Pediatric Participants From Birth to < 1 Year With Influenza-Like Symptoms (NCT03653364). [Internet; cited 2019 August]. Available from: https://clinicaltrials.gov/ct2/show/NCT03653364.

[10] ClinicalTrials.gov. Study to Assess Efficacy and Safety of Baloxavir Marboxil In Combination With Standard-of-Care Neuraminidase Inhibitor In Hospitalized Participants With Severe Influenza (NCT03684044). [Internet; cited 2019 August]. Available from: https://clinicaltrials.gov/ct2/show/NCT03684044.

[11] ClinicalTrials.gov. Study to Assess the Efficacy of Baloxavir Marboxil Versus Placebo to Reduce Onward Transmission of Influenza A or B in Households (NCT03969212). [Internet; cited 2019 August]. Available from: https://clinicaltrials.gov/ct2/show/NCT03969212.