Single Dose Baloxavir marboxil (Xofluza) Has Potential To Improve Treatment of High-Risk Flu

MedicalResearch.com Interview with:

Mark D. Eisner, MD, MPH Vice President, Product Development Immunology Infectious Disease and Ophthalmology Genentech 

Dr. Eisner

Mark D. Eisner, MD, MPH
Vice President, Product Development Immunology
Infectious Disease and Ophthalmology
Genentech 

MedicalResearch.com: What is the background for this study?

Response: CAPSTONE-2 is a Phase III multicenter, randomized, double-blind study that evaluated the efficacy and safety of a single dose of baloxavir marboxil compared with placebo and oseltamivir in people 12 years and older who are at a high risk of complications from the flu. The Centers for Disease Control and Prevention (CDC) defines people at high risk for serious flu complications to include adults 65 years of age or older, or those who have conditions such as asthma, chronic lung disease, morbid obesity or heart disease.

A total of 2,184 participants enrolled in the study and were randomly assigned to receive a single, oral dose of 40 mg or 80 mg of baloxavir marboxil (according to body weight), placebo or 75 mg of oseltamivir twice daily for five days. The primary objective of the study evaluated the efficacy of a single dose of baloxavir marboxil compared with placebo by measuring the time to improvement of influenza symptoms. Key secondary endpoints compared outcomes in baloxavir marboxil versus placebo or oseltamivir – these included time to resolution of fever, time to cessation of viral shedding, infectious virus detection in swabs of the nose and throat, prescription of antibiotics and influenza-related complications.

Genentech announced initial results from the study on July 16, 2018 but the full data was presented for the first time during a late-breaking oral presentation at the annual IDWeek meeting in San Francisco, CA on October 6, 2018.

Baloxavir marboxil is a first-in-class, single-dose investigational oral medicine with a novel proposed mechanism of action designed to target the influenza A and B viruses, including oseltamivir-resistant strains and avian strains (e.g. H7N9, H5N1). Baloxavir marboxil is the first potential influenza treatment to demonstrate a clinically meaningful benefit for people highly vulnerable to serious influenza complications in clinical trials.

The FDA accepted a New Drug Application (NDA) and granted Priority Review to baloxavir marboxil as a single-dose, oral treatment for acute, uncomplicated influenza in people 12 years and older. The NDA was based on results from the Phase III CAPSTONE-1 study of a single dose of baloxavir marboxil compared with placebo or oseltamivir 75 mg, twice daily for five days, in otherwise healthy people with the flu. Results from a placebo-controlled Phase II study in otherwise healthy people with the flu were included as supporting data in the NDA. The FDA is expected to make a decision on approval by December 24, 2018. Continue reading

Study Suggests Tamiflu Does Not Increase Risk of Suicide

MedicalResearch.com Interview with:

James W. Antoon, MD, PhD, FAAP Assistant Professor of Clinical Pediatrics University of Illinois at Chicago Associate Medical Director, Pediatric Inpatient Unit Children's Hospital, University of Illinois Hospital & Health Sciences System Chicago, IL 60612 

Dr. Antoon

James W. Antoon, MD, PhD, FAAP
Assistant Professor of Clinical Pediatrics
University of Illinois at Chicago
Associate Medical Director, Pediatric Inpatient Unit
Children’s Hospital, University of Illinois Hospital & Health Sciences System
Chicago, IL 60612 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Oseltamivir, commonly known as Tamiflu, is the only commercially available medication FDA approved to treat the flu.  Since the 2009 H1N1 flu epidemic pediatric prescriptions for Tamiflu have soared.  In the United States, about 40% of Tamiflu prescriptions are given to children less than 16 years of age.  Following reports of abnormal behavior, such as hallucinations, self-injury and suicide attempts in adolescents on Tamiflu, the FDA placed a new warning about these neuropsychiatric symptoms on the drug label.  Whenever the FDA puts out label warning about a drug, doctors and the public take notice. Whether Tamiflu truly causes these side effects is unclear.  For this study we chose to focus on the most consequential of those reports: suicide.

The potential link between a drug and suicide is a particularly difficult topic to study for a number of reasons. There are things that happen together or at the same time that can influence someone to attempt suicide and it is very difficult to know which thing is actually having an affect. In our study, other things that can influence suicide are socioeconomic status, mental health, trauma, abuse, among others.  Separating the effects of these confounders can be difficult. It is also possible that the disease itself, which in this case is the flu, causes the effect of suicide. Finally, and luckily, suicide is rare. Our database had 12 million children per year and over five year 21,000 attempted suicide. Of those, only 251 were taking Tamiflu.

To get past these issues, we took advantage of a growing drug safety research collaboration between the Departments of Pediatrics and Pharmacy at our institution.  Previous studies have compared those on Tamiflu to those not on Tamiflu to see if there are more side effects in the Tamiflu group.  Our team utilized a novel study method called a case-crossover design. What’s different about this study is that we used each patient as their own comparison.  In other words, we compared each patient to themselves rather than a different group of people.  We essentially studied how patients behaved when the Tamiflu was in their system compared to other l periods where they were not on Tamiflu.  This allowed use to account for the personal differences noted above like mental health and socioeconomic status.   We also compared those children with flu who got Tamiflu and those with flu who did not get Tamiflu to see if the infection itself could be associated with increased suicide.

After accounting for all these variables, we did not find any an association between Tamiflu exposure and suicide. Our findings suggest that Tamiflu does NOT increase the risk of suicide in children or teenagers.

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Balovaptan Has Potential to Improve Social Interaction and Communication in Autism Spectrum Disorder

MedicalResearch.com Interview with:

Dr Kevin Sanders, MD Principle Medical Director-Product Development Neuroscience Assistant Professor, Departments of Psychiatry and Pediatrics Vanderbilt University

Dr. Sanders

Dr Kevin Sanders, MD
Principle Medical Director-Product Development Neuroscience
Assistant Professor, Departments of Psychiatry and Pediatrics
Vanderbilt University 

MedicalResearch.com: What is the background for this announcement? 

Response: The FDA has granted Roche Breakthrough Therapy Designation for its investigational oral medicine balovaptan (previously known as RG7314), a vasopressin 1a (V1a) receptor antagonist for individuals with autism spectrum disorder (ASD).

FDA Breakthrough Therapy Designation for balovaptan is primarily based on efficacy findings in the VANILLA (Vasopressin ANtagonist to Improve sociaL communication in Autism) study, a Phase II trial of balovaptan in adults with ASD. Trial results were first presented at the International Congress for Autism Research (IMFAR) in May 2017. Treatment effects were observed on the Vineland-II (secondary endpoint) and also demonstrated that balovaptan was safe and well tolerated by the subjects in the study. The Vineland-II is a scale that measures socialization, communication and daily living skills. This data was presented to the FDA and is part of the basis of the Breakthrough Designation.  Continue reading