We’re glad to see you’re enjoying ReachMD…
but how about a more personalized experience?
Announcer:
You're listening to The Drug Report on ReachMD, hosted by Linda Bernstein, Pharm.D., Clinical Professor on the Volunteer Faculty of the School of Pharmacy, University of California, San Francisco.
Dr. Bernstein:
Welcome to The Drug Report.
Baloxavir marboxil (brand name, Xofluza®) is an oral anti-influenza drug, the prodrug of baloxavir acid. It is characterized as a first-in-class, small molecule inhibitor of the polymerase acidic (PA) protein subunit of the influenza virus polymerase complex. Baloxavir (after conversion to baloxavir acid) acts to block influenza virus replication by inhibiting the cap-dependent endonuclease activity of the PA protein.
In 2018, the U.S. Food and Drug Administration approved Xofluza (baloxavir marboxil) for the treatment of acute uncomplicated influenza in patients 12 years of age and older who have been symptomatic for no more than 48 hours. Approval was granted to Shionogi & Co., Ltd.
The safety and efficacy of Xofluza, taken as a single oral dose, was demonstrated in two randomized controlled clinical trials of 1,832 patients where participants were assigned to receive either Xofluza, a placebo, or another antiviral flu treatment within 48 hours of experiencing flu symptoms. In both trials, patients treated with Xofluza had a shorter time to alleviation of symptoms compared with patients who took the placebo. In the second trial, there was no difference in the time to alleviation of symptoms between subjects who received Xofluza and those who received the other flu treatment.
The U.S. Food and Drug Administration expanded the approved indication for Xofluza (baloxavir marboxil) on November 23, 2020, to include post-exposure prevention of influenza for patients 12 years of age and older after contact with an individual who has the flu. Xofluza, previously available only in tablet form, is also now available as granules for mixing in water as a suspension for oral or enteral use.
Debra Birnkrant, M.D., director of the Division of Antiviral Products in the FDA’s Center for Drug Evaluation and Research stated: “This expanded indication for Xofluza will provide an important option to help prevent influenza just in time for a flu season that is anticipated to be unlike any other because it will coincide with the coronavirus pandemic. Americans will have to be more vigilant than ever as these viruses spread concurrently.”
Xofluza’s safety and efficacy for post-influenza exposure prevention is supported by one randomized, double-blind, controlled trial in which 607 subjects, 12 years of age and older who were exposed to a person with influenza in their household, received either a single dose of Xofluza or a single dose of a placebo. Of these 607 subjects, 303 received Xofluza and 304 received the placebo. The trial’s primary endpoint was the proportion of subjects who were infected with influenza virus and presented with fever and at least one respiratory symptom from day 1 to day 10. Of those who received Xofluza, 1% of subjects met these criteria, compared to 13% of subjects who received a placebo for the clinical trial.
The most common side effects of Xofluza include diarrhea, bronchitis, nausea, sinusitis and headache. In randomized clinical trials there was evidence of development of reduced susceptibility in some patients treated with baloxavir.
Hypersensitivity, including anaphylaxis (allergic reaction), can occur in patients taking Xofluza. Patients should not take Xofluza if they have had a known hypersensitivity reaction to the drug. Xofluza should not be co-administered with dairy products, calcium-fortified beverages, or laxatives, antacids, or oral supplements containing calcium, iron, magnesium, selenium, aluminum or zinc.
The FDA granted the approval of Xofluza in this expanded indication to Genentech USA, Inc.
Here are some additional study highlights of recently published research about baloxavir.
A post marketing surveillance of more than 3000 patients studied the safety and efficacy of baloxavir marboxil for the treatment of influenza in Japanese clinical practice. The study published in July 2020 in the Journal of Infectious Disease and Chemotherapy involved 688 Japanese hospitals or clinics (from March 2018 to March 2019). They enrolled patients of any age with influenza A or B who received a single, weight-based dose of baloxavir. Adverse drug reactions (ADRs) were seen in 11.2% of 3094 patients during the 7-day observation period; the most common ADR was diarrhea (6.1%). ADRs were more common in children aged <12 years (14.1%) than in adults (10.0%). Almost all ADRs were non-serious. Median time to alleviation of symptoms was 2.5 days (overall, influenza A, and influenza B groups). Median time to resolution of fever was 1.5 days (overall, influenza A, and influenza B groups). Biphasic fever (i.e., increased temperature after previous fever resolution) was seen in 6.7% of patients overall and 28.6% of patients <6 years infected with influenza B, similar to rates published elsewhere with other influenza drugs and in untreated influenza. The authors concluded that the study suggests that baloxavir is well tolerated and effective regardless of patient age or influenza virus type.
The Lancet Infectious Diseases, October 2020 issue described a double-blind, placebo-controlled and oseltamivir-controlled trial in outpatients aged 12 years and older. The study found that single dose baloxavir has superior efficacy to placebo and similar efficacy to oseltamivir for ameliorating influenza symptoms in high-risk outpatients. The safety of baloxavir was similar to placebo. The authors stated that this study supports early therapy for patients at high risk of complications of influenza to speed clinical recovery and reduce complications. Both studies were funded by or involved employees of Shionogi.
For The Drug Report, I’m Pharmacist Dr. Linda Bernstein.
Announcer:
To access this episode and others from The Drug Report, visit ReachMD.com/drugreport, where you can be part of the knowledge. Thanks for listening.
Ready to Claim Your Credits?
You have attempts to pass this post-test. Take your time and review carefully before submitting.
Good luck!
To prevent the flu from spreading concurrently with COVID-19, The U.S. Food and Drug Administration has expanded the approved indication for baloxavir marboxil to include post-exposure prevention of influenza. On this episode of The Drug Report, Dr. Linda Bernstein dives into this oral anti-influenza drug.
Published December 2, 2020
Announcer:
You're listening to The Drug Report on ReachMD, hosted by Linda Bernstein, Pharm.D., Clinical Professor on the Volunteer Faculty of the School of Pharmacy, University of California, San Francisco.
Dr. Bernstein:
Welcome to The Drug Report with a special focus on the COVID-19 pandemic.
Researchers all over the world are trying many novel approaches to conquering the Novel Coronavirus, cause of the current deadly pandemic. Let’s look at a few of these approaches and what they may mean for today and potential viral mutations going forward.
Celltrion Group, through a partnership with the Korea Centers for Disease Control and Prevention (KCDC), narrowed their top neutralizing antibody candidates to 14 of the most powerful and will begin cell-line development. They hope to roll out mass production of the therapeutic antibody and, together with the KCDC, conduct efficacy and toxicity testing in mice and non-human primates. Ki-Sung Kwon, Head of R&D Unit at Celltrion said, “These antibodies can recognize multiple epitopes, thus increasing the probability of nonspecific antigen binding. We anticipate moving to first-in-human clinical trials in July. We are also on track with the development of a ‘super antibody’ or ‘an antibody cocktail’ and the launch of a rapid self-testing diagnostic kit in the summer of this year.”
Regeneron is trying two approaches to COVID-19. Based on recent clinical data from studies in China with another IL-6 inhibitor, they believe there is a potential role for Kevzara® (sarilumab) in the treatment of severe and critical hospitalized patients with COVID-19. Together with Sanofi, they are conducting controlled clinical trials to evaluate Kevzara in this setting on an investigational basis.The global trial program is now enrolling patients at medical centers in the United States, Italy, Spain, Germany, France, Canada, and Russia.
Regeneron is also looking to develop a novel multi-antibody cocktail that can be administered as prophylaxis before exposure to the SARS-CoV-2 virus or as treatment for those already infected. Hundreds of virus-neutralizing, fully human antibodies have been isolated from the company's mice which have been genetically modified to have a human immune system. Regeneron has also isolated antibodies from humans who have recovered from COVID-19 in order to maximize the pool of potentially potent antibodies. From this large pool of candidates, Regeneron will select the top two antibodies for a 'cocktail' treatment based on potency and binding ability to the SARS-CoV-2 spike protein, as well as other desirable qualities. Using a multi-antibody approach allows for targeting of different parts of the virus and may help protect against multiple viral variants. They used similar technologies to rapidly develop a treatment for Ebola virus infection, which is currently under review by the U.S. Food and Drug Administration.
Eli Lilly, in conjunction with the National Institute of Allergy and Infectious Diseases, is planning to test rheumatoid arthritis drug Olumiant (baricitinib), a Janus kinase (JAK) inhibitor, in patients hospitalized with COVID-19. The study is starting this month in the U.S., and investigators plan expanded testing to Europe and Asia.
Meanwhile, Lilly also unveiled plans to test an investigational monoclonal antibody, LY3127804, in pneumonia patients hospitalized with COVID-19. That trial is starting later this month in the U.S.
Roche has announced that the US Food and Drug Administration (FDA) has formally approved its phase 3 trial of Actemra in severely ill COVID-19 patients who have been hospitalized with pneumonia. Actemra (tocilizumab) – an interleukin-6 inhibitor – has already been approved in China for the treatment of patients infected with the novel coronavirus disease who have developed serious lung damage and also have elevated levels of IL-6 in the blood. Previous research has suggested that elevated IL-6, a biomarker for inflammation and a high-level immune response, is associated with a higher mortality in people with community-acquired pneumonia.
Japanese company Fujifilm has launched a Phase II clinical trial of its influenza drug Avigan (favipiravir) to treat COVID-19 patients in the US. It will also be tested on 80 patients at Hadassah Hospital in Israel. Approved in 2014 in Japan, Avigan specifically targets RNA polymerase required for influenza virus replication. This mechanism is also expected to have an antiviral effect on the novel coronavirus, which is a single-stranded RNA virus similar to influenza and requires viral RNA polymerase. For the new study in the US, around 50 coronavirus patients will be enrolled at Brigham and Women’s Hospital, Massachusetts General Hospital, and the University of Massachusetts Medical School. The trial will evaluate the drug’s safety and efficacy as a potential COVID-19 therapy.
Finally, Johnson & Johnson announced the selection of a lead COVID-19 vaccine candidate from constructs it has been working on since January 2020 and by rapid scaling of the company’s manufacturing capacity they hope to provide a global supply of more than one billion doses of a vaccine. The company expects to initiate human clinical trials of its lead vaccine candidate at the latest by September 2020 and anticipates the first batches of a COVID-19 vaccine could be available for emergency use authorization in early 2021, a pace they state is substantially accelerated in comparison to the typical vaccine development timeframe.
For more information on COVID-19 treatment and prevention studies, see clinicaltrials.gov.
For The Drug Report, I’m pharmacist Dr. Linda Bernstein.
Announcer:
To access this episode and others from The Drug Report, visit ReachMD.com/drugreport, where you can be part of the knowledge. Thanks for listening.
To prevent the flu from spreading concurrently with COVID-19, The U.S. Food and Drug Administration has expanded the approved indication for baloxavir marboxil to include post-exposure prevention of influenza. On this episode of The Drug Report, Dr. Linda Bernstein dives into this oral anti-influenza drug.
Published December 2, 2020
Announcer:
You're listening to The Drug Report on ReachMD, hosted by Linda Bernstein, Pharm.D., Clinical Professor on the Volunteer Faculty of the School of Pharmacy, University of California, San Francisco.
Dr. Bernstein:
Welcome to The Drug Report with a special focus on the COVID-19 pandemic.
Researchers all over the world are trying many novel approaches to conquering the Novel Coronavirus, cause of the current deadly pandemic. Let’s look at a few of these approaches and what they may mean for today and potential viral mutations going forward.
Celltrion Group, through a partnership with the Korea Centers for Disease Control and Prevention (KCDC), narrowed their top neutralizing antibody candidates to 14 of the most powerful and will begin cell-line development. They hope to roll out mass production of the therapeutic antibody and, together with the KCDC, conduct efficacy and toxicity testing in mice and non-human primates. Ki-Sung Kwon, Head of R&D Unit at Celltrion said, “These antibodies can recognize multiple epitopes, thus increasing the probability of nonspecific antigen binding. We anticipate moving to first-in-human clinical trials in July. We are also on track with the development of a ‘super antibody’ or ‘an antibody cocktail’ and the launch of a rapid self-testing diagnostic kit in the summer of this year.”
Regeneron is trying two approaches to COVID-19. Based on recent clinical data from studies in China with another IL-6 inhibitor, they believe there is a potential role for Kevzara® (sarilumab) in the treatment of severe and critical hospitalized patients with COVID-19. Together with Sanofi, they are conducting controlled clinical trials to evaluate Kevzara in this setting on an investigational basis.The global trial program is now enrolling patients at medical centers in the United States, Italy, Spain, Germany, France, Canada, and Russia.
Regeneron is also looking to develop a novel multi-antibody cocktail that can be administered as prophylaxis before exposure to the SARS-CoV-2 virus or as treatment for those already infected. Hundreds of virus-neutralizing, fully human antibodies have been isolated from the company's mice which have been genetically modified to have a human immune system. Regeneron has also isolated antibodies from humans who have recovered from COVID-19 in order to maximize the pool of potentially potent antibodies. From this large pool of candidates, Regeneron will select the top two antibodies for a 'cocktail' treatment based on potency and binding ability to the SARS-CoV-2 spike protein, as well as other desirable qualities. Using a multi-antibody approach allows for targeting of different parts of the virus and may help protect against multiple viral variants. They used similar technologies to rapidly develop a treatment for Ebola virus infection, which is currently under review by the U.S. Food and Drug Administration.
Eli Lilly, in conjunction with the National Institute of Allergy and Infectious Diseases, is planning to test rheumatoid arthritis drug Olumiant (baricitinib), a Janus kinase (JAK) inhibitor, in patients hospitalized with COVID-19. The study is starting this month in the U.S., and investigators plan expanded testing to Europe and Asia.
Meanwhile, Lilly also unveiled plans to test an investigational monoclonal antibody, LY3127804, in pneumonia patients hospitalized with COVID-19. That trial is starting later this month in the U.S.
Roche has announced that the US Food and Drug Administration (FDA) has formally approved its phase 3 trial of Actemra in severely ill COVID-19 patients who have been hospitalized with pneumonia. Actemra (tocilizumab) – an interleukin-6 inhibitor – has already been approved in China for the treatment of patients infected with the novel coronavirus disease who have developed serious lung damage and also have elevated levels of IL-6 in the blood. Previous research has suggested that elevated IL-6, a biomarker for inflammation and a high-level immune response, is associated with a higher mortality in people with community-acquired pneumonia.
Japanese company Fujifilm has launched a Phase II clinical trial of its influenza drug Avigan (favipiravir) to treat COVID-19 patients in the US. It will also be tested on 80 patients at Hadassah Hospital in Israel. Approved in 2014 in Japan, Avigan specifically targets RNA polymerase required for influenza virus replication. This mechanism is also expected to have an antiviral effect on the novel coronavirus, which is a single-stranded RNA virus similar to influenza and requires viral RNA polymerase. For the new study in the US, around 50 coronavirus patients will be enrolled at Brigham and Women’s Hospital, Massachusetts General Hospital, and the University of Massachusetts Medical School. The trial will evaluate the drug’s safety and efficacy as a potential COVID-19 therapy.
Finally, Johnson & Johnson announced the selection of a lead COVID-19 vaccine candidate from constructs it has been working on since January 2020 and by rapid scaling of the company’s manufacturing capacity they hope to provide a global supply of more than one billion doses of a vaccine. The company expects to initiate human clinical trials of its lead vaccine candidate at the latest by September 2020 and anticipates the first batches of a COVID-19 vaccine could be available for emergency use authorization in early 2021, a pace they state is substantially accelerated in comparison to the typical vaccine development timeframe.
For more information on COVID-19 treatment and prevention studies, see clinicaltrials.gov.
For The Drug Report, I’m pharmacist Dr. Linda Bernstein.
Announcer:
To access this episode and others from The Drug Report, visit ReachMD.com/drugreport, where you can be part of the knowledge. Thanks for listening.
Stay current with the best on medical education
