New Option for Influenza: Results of CAPSTONE-1 for Baloxavir

Baloxavir is the newest single-dose treatment for the treatment of influenza, now available in United States. In CAPSTONE-1, baloxavir was compared to oseltamivir in its efficacy to alleviate influenza symptoms. Let’s take a closer look.

Slide1

CAPSTONE-1 consists of two randomized, double-blind, controlled trials with healthy outpatients with acute uncomplicated influenza.

The first one was a phase 2 trial dose-ranging (10-40mg) placebo-controlled trial and the second is one where Baloxavir was compared to oseltamivir (75mg po BID for 5 days).

Here’s a quick summary:

Patient Inclusion Criteria:

  • Age ≥ 12 yrs and ≤ 64 years of age
  • Had a fever (axillary temperature ≥ 38.0°C) in the pre-dose examinations or > 4 hours after dosing of antipyretics if there were taken
  • At least one of the following systemic symptoms associated with influenza
    • Headache
    • Feverishness or chills
    • Muscle or joint pain
    • Fatigue
  • At least one of the following respiratory symptoms of at least moderate severity
    • Cough
    • Sore Throat
    • Nasal congestion
  • A symptom of duration of no more than 48 hours

A positive rapid antigen test was an entry criterion for the phase 2 trial but  not the phase 3 trial.

Patient Exclusion Criteria:

  • Patients with severe influenza virus infection requiring inpatient treatment
  • Patients age > 20 with known allergy to oseltamivir
  • Patients with any of the following risk factors
    • Pregnant women or within 2 weeks post-partum
    • Residents of long term care facilities (e.g. welfare facilities for the elderly, nursing homes)
    • Chronic respiratory disease including bronchial asthma
    • Neurological and neurodevelopmental disorders (e.g. cerebral palsy, epilepsy, stroke, intellectual disability, moderate to severe developmental delay, muscular dystrophy, spinal cord injury)
    • Heart disease (e.g. congenital heart disease, congestive heart failure, coronary artery disease), excluding hypertension without any other heart related symptoms
    • American Indians and Alaskan natives
    • Blood disorders (e.g. sickle cell disease)
    • Endocrine disorder (including diabetes mellitus)
    • Kidney disorders
    • Liver disorders
    • Metabolic disorders
    • Compromised immune system (e.g. HIV)
    • Morbid obesity (BMI ≥ 40)
  • Weighing less than 40kg
  • Those with illness resulting in hospitalization (please refer to supplemental appendix for a complete list)

Slide2

Primary efficacy endpoint – the time to alleviation of influenza symptoms in the intention-to-treat infected population. This is defined as the time from the start of the trial regimen to the time when all seven influenza-related symptoms were rated by the patient as absent or mild for at least 21.5 hours.

Secondary clinical endpoints include:

  • time to resolution of fever
  • time to return to usual health
  • newly occurring complications leading to antibiotic use

Clinical and Laboratory Monitoring

Patients assessed the severity of the seven influenza-associated symptoms on a 4-point scale (0= no symptoms; 3 = severe symptoms):

  1. Cough
  2. Sore throat
  3. Headache
  4. Nasal Congestion
  5. Feverishness or chills
  6. Muscle or joint pain
  7. Fatigue

Results:

Phase 2 trial:

  • The median time to alleviation of influenza symptoms was 23.4 to 28.2 hours shorter in the baloxavir groups than in the placebo group (p < 0.05).

Phase 3 trial:

  • The intention-to-treat infected population included 1064 patients;
    • 84.8-88.1% of the patients in each group had influenza A (H3N2) infection
  • The median time to alleviation of symptoms was 53.7 hours (95% CI, 49.5 to 58.5) with baloxavir, as compared with 80.2 hours (95% CI, 72.6 to 87.1) with placebo (p>0.001).
  • The time to alleviation of symptoms was similar with baloxavir and oseltamivir.
  • Baloxavir was associated with greater reductions in viral load 1 day after initiation of the regimen than placebo or oseltamivir.

CAPSTONE-1 result

Slide5

Slide6

Authors’ conclusions:

Single-dose baloxavir was without evident safety concerns, was superior to placebo in alleviating influenza symptoms and was superior to both oseltamivir and placebo in reducing viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza.

My thoughts:

  • This study was conducted in healthy individuals  (overall median age is ~ 32 – 38 yrs old) in an outpatient setting. I will also add that the results are based on population with a high percentage from Japan (~ at least 75% Japanese).  It is questionable if the results can truly extrapolate to North American.
  • Because of the exclusion criteria, these results cannot be extrapolated to those living in nursing homes or with risk factors such as asthma, chronic lung disease, diabetes and heart disease. Will need to wait for the results of CAPTSTONE-2 to comment.
  • Based on this study, baloxavir is similar to oseltamivir in its ability to alleviate influenza symptoms. Although it can reduce viral load faster, this is likely a function of the pharmacokinetic properties (1-single dose treatment vs. 5-day treatment with oseltamivir). Still, I don’t think this translate into any meaningful difference clinically.
  • The cost of baloxavir is $150 US (vs. $100 for Oseltamivir). With coupons, the cost of oseltamivir may be as low as $30. In Canada, baloxavir is not yet approved. The approximate cost of oseltamivir 75mg po BID x 5 days is about $35 with dispensing fee.
  • Even if baloxavir is approved in Canada, it is likely reserved for those with private insurance and has the means to pay for it. The real benefit is that it is a single-dose treatment so eliminating any concerns with compliance.

Other notes:

Based on the US Prescribing information of baloxavir (Xofluza):

  • It is available as 10mg and 20mg tablet
  • Indicated for Influenza Types A and B
  • Usual dose for adults and children over 12 years age is two tablets (20mg x 2 = 40mg) as a single dose
  • If over 80kg, may need 4 x 20mg = 80mg
  • For children younger than 12 years:
    • 40kg or more = two 20mg tablets ( = 40mg of Baloxavir)
    • less than 40kg and 20kg or more = one 20mg tablet ( = 20mg of Baloxavir)
    • less than 20kg and 10kg or more = one 10mg tablet ( = 10mg of Baloxavir)

Thank you for reading my post.

 

 

 

 

 

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drugopinions

My name is Cynthia Leung and I am a practicing pharmacist in Kingston Ontario, Canada. This blog is for me to share my ideas, opinions and perspectives on how medications are used in our health care system. Note that these posts are my own opinions and do not represent the opinions of my current or former employers and / or organizations that I may belong to. Any possible case scenarios described in my posts would be modified to maintain patient confidentiality. This blog is not a platform for professional advise for patients or health care providers and the content is not meant to support any clinical decisions or replace professional opinions. Also the images are either taken or created by the author, or adapted with permission. I hope you will enjoy reading my posts!

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