Smart money says that whatever trump thinks, go the other way.
“A study of 96,000 hospitalized coronavirus patients on six continents found that those who received an antimalarial drug promoted by President Trump as a “game changer” in the fight against the virus had a significantly higher risk of death compared with those who did not.
People treated with hydroxychloroquine, or the closely related drug chloroquine, were also more likely to develop a type of irregular heart rhythm, or arrhythmia, that can lead to sudden cardiac death, it concluded.”
Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial
By Feng-Cai Zhu, Yu-Hua Li, Xu-Hua Guan, Li-Hua Hou, Wen-Juan Wang, Jing-Xin Li, et al.
Summary
Background
A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain.
Methods
We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5 × 1010, 1 × 1011, and 1·5 × 1011 viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127.
Findings
Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36·3 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse reaction within the first 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 [46%]), fatigue (47 [44%]), headache (42 [39%]), and muscle pain (18 [17%]. Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination.
Interpretation
The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation.
Welcome to Angry Bear. Every first comment goes to moderation to keep spammers, spam, and advertising out. Thank you for your comment. If you keep the same logon, I do not have to keep approving you. 🙂
Bill
So this is something to treat Adenoviruses a group of viruses that typically cause respiratory illnesses, such as a common cold, conjunctivitis (an infection in the eye that is sometimes called pink eye), croup, bronchitis, or pneumonia. In children, adenoviruses usually cause infections in the respiratory tract and intestinal tract.
This would be typical of what presents in Covid 19 except in a milder form.
Gilead should ditch remdesivir and focus on its simpler and safer ancestor
By VICTORIA C. YAN and FLORIAN L. MULLER
In the midst of a pandemic like Covid-19, for which there are no FDA-approved drug treatments, hope is important. That’s one reason why remdesivir, an antiviral drug that Gilead Sciences originally made to fight Ebola, has been propelled into the spotlight with the hope that it can stop, or at least curtail, the ravages of SARS-CoV-2, the virus that causes Covid-19.
Data from the open-label SIMPLE trial, sponsored by Gilead, and the randomized controlled Adaptive Covid-19 Treatment Trial, sponsored by the National Institute of Allergy and Infectious Diseases, show that remdesivir may accelerate recovery rates among patients with advanced Covid-19. The drug’s modest effects are a far cry from the strong antiviral activity it demonstrated in preclinical primate models of coronavirus (both MERS and SARS-CoV-2). Yet that has been enough for the Food and Drug Administration to grant emergency use authorization for remdesivir and for the Japanese Ministry of Health, Labour, and Welfare to approve it for the treatment of Covid-19.
As chemists, we are troubled by the challenges to mass producing remdesivir. We aren’t alone. On the day that results from the two trials emerged, Gilead CEO Daniel O’Day praised the chemists behind the drug, saying he is “proud of the team because this is a complicated chemical process. It takes many, many steps.”
But does it really have to be that complicated? O’Day’s admission is interesting given that Gilead has another compound in its pipeline that is easier to make, has been shown to be effective against coronavirus in animal models, and is potentially as effective as remdesivir, if not more so….
There is reason to wonder whether there is a Gilead drug other than remdesivir that could be as or more effective and much simpler to produce. The problem being that the possible alternative drug has less remaining patent protection and is of less interest to Gilead.
Gilead’s remdesivir was initially declared an orphan drug which gives it a special status of being a drug to treat rare diseases (I will keep this simple as you probably already know this). The advantages to being declared an orphan drug are tax incentives, longer exclusivity for patent and marketing rights, research subsidies, and creating a government-run enterprise to engage in research and development. ~50% of R&D and startup are tax deductible. When demand such as what has been caused by the Pandemic increases, Pharma can cover costs in 5 years (WHO) through risk-adjusted sales. Gilead would rather have the latter that the orphan drug moniker.
In other words there, is money to be made in remdesivir. Their costs of production already covered by prior sales. It would make sense to go with the less complicated process of the GS-441524. I do not think there is any reason for Dean or anyone to wonder why Gilead is doing remdesivir. Its for the money.
As for the promising Chinese vaccine, development is by a Chinese team that previously produced a SARS vaccine. Chen Wei, the team leader, is a biology professor from the Academy of Military Medical Sciences and a member of the Chinese Academy of Engineering. The Chinese vaccine will be tested in several countries working with WHO scientists. A successful vaccine will be public.
I have some issues with Gilead also. They are setting themselves up. I am not sure what the recently passed Cures Act may do for them also. Been following the HCQ issues mostly.
Isn’t this the same Gilead that bought the cure for Hep-C and proceeded to sell a treatment that costs $200 to manufacture for $100,000 — take it or leave it? Together with other pharma companies and their copy cats Gilead and friends want $250 billion over 20 patent run down years NOT to wipe out Hep-C in one year.
With remdesivir I thought that Gilead would be shamed during this pandemic from gouging — might even have a little morals about it. Guessed wrong on both quarters.
I tend to try enjoying themed video evenings around holidays. Usually favor re-watching favorite “War is Hell” movies for Memorial Day weekend. But this year we watched this genuinely interesting feature: https://www.imdb.com/title/tt6018306/?ref_=nv_sr_srsg_0
“Last Flag Flying” features Steve Carell, Bryan Cranston, and Laurence Fishburne as three Vietnam era vets who re-unite to bury a dead son. Not one of Richard Linklater’s best known films but it will be added to a list of favorite movies for this holiday. Thoughtful, interesting and well done. It made me think about patriotism and service in ways I hadn’t considered before. Highest recommendation.
Smart money says that whatever trump thinks, go the other way.
“A study of 96,000 hospitalized coronavirus patients on six continents found that those who received an antimalarial drug promoted by President Trump as a “game changer” in the fight against the virus had a significantly higher risk of death compared with those who did not.
People treated with hydroxychloroquine, or the closely related drug chloroquine, were also more likely to develop a type of irregular heart rhythm, or arrhythmia, that can lead to sudden cardiac death, it concluded.”
https://www.washingtonpost.com/health/2020/05/22/hydroxychloroquine-coronavirus-study/
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31208-3/fulltext
May 22, 2020
Safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 vectored COVID-19 vaccine: a dose-escalation, open-label, non-randomised, first-in-human trial
By Feng-Cai Zhu, Yu-Hua Li, Xu-Hua Guan, Li-Hua Hou, Wen-Juan Wang, Jing-Xin Li, et al.
Summary
Background
A vaccine to protect against COVID-19 is urgently needed. We aimed to assess the safety, tolerability, and immunogenicity of a recombinant adenovirus type-5 (Ad5) vectored COVID-19 vaccine expressing the spike glycoprotein of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) strain.
Methods
We did a dose-escalation, single-centre, open-label, non-randomised, phase 1 trial of an Ad5 vectored COVID-19 vaccine in Wuhan, China. Healthy adults aged between 18 and 60 years were sequentially enrolled and allocated to one of three dose groups (5 × 1010, 1 × 1011, and 1·5 × 1011 viral particles) to receive an intramuscular injection of vaccine. The primary outcome was adverse events in the 7 days post-vaccination. Safety was assessed over 28 days post-vaccination. Specific antibodies were measured with ELISA, and the neutralising antibody responses induced by vaccination were detected with SARS-CoV-2 virus neutralisation and pseudovirus neutralisation tests. T-cell responses were assessed by enzyme-linked immunospot and flow-cytometry assays. This study is registered with ClinicalTrials.gov, NCT04313127.
Findings
Between March 16 and March 27, 2020, we screened 195 individuals for eligibility. Of them, 108 participants (51% male, 49% female; mean age 36·3 years) were recruited and received the low dose (n=36), middle dose (n=36), or high dose (n=36) of the vaccine. All enrolled participants were included in the analysis. At least one adverse reaction within the first 7 days after the vaccination was reported in 30 (83%) participants in the low dose group, 30 (83%) participants in the middle dose group, and 27 (75%) participants in the high dose group. The most common injection site adverse reaction was pain, which was reported in 58 (54%) vaccine recipients, and the most commonly reported systematic adverse reactions were fever (50 [46%]), fatigue (47 [44%]), headache (42 [39%]), and muscle pain (18 [17%]. Most adverse reactions that were reported in all dose groups were mild or moderate in severity. No serious adverse event was noted within 28 days post-vaccination. ELISA antibodies and neutralising antibodies increased significantly at day 14, and peaked 28 days post-vaccination. Specific T-cell response peaked at day 14 post-vaccination.
Interpretation
The Ad5 vectored COVID-19 vaccine is tolerable and immunogenic at 28 days post-vaccination. Humoral responses against SARS-CoV-2 peaked at day 28 post-vaccination in healthy adults, and rapid specific T-cell responses were noted from day 14 post-vaccination. Our findings suggest that the Ad5 vectored COVID-19 vaccine warrants further investigation.
anne:
Welcome to Angry Bear. Every first comment goes to moderation to keep spammers, spam, and advertising out. Thank you for your comment. If you keep the same logon, I do not have to keep approving you. 🙂
Bill
So this is something to treat Adenoviruses a group of viruses that typically cause respiratory illnesses, such as a common cold, conjunctivitis (an infection in the eye that is sometimes called pink eye), croup, bronchitis, or pneumonia. In children, adenoviruses usually cause infections in the respiratory tract and intestinal tract.
This would be typical of what presents in Covid 19 except in a milder form.
Anne:
This is a vaccine from what I quickly scanned. Who other than China developed it? ” recombinant adenovirus type-5 vectored COVID-19 vaccine”
https://www.statnews.com/2020/05/14/gilead-should-ditch-remdesivir-and-focus-on-its-simpler-safer-ancestor/comment-page-1/
May 14, 2020
Gilead should ditch remdesivir and focus on its simpler and safer ancestor
By VICTORIA C. YAN and FLORIAN L. MULLER
In the midst of a pandemic like Covid-19, for which there are no FDA-approved drug treatments, hope is important. That’s one reason why remdesivir, an antiviral drug that Gilead Sciences originally made to fight Ebola, has been propelled into the spotlight with the hope that it can stop, or at least curtail, the ravages of SARS-CoV-2, the virus that causes Covid-19.
Data from the open-label SIMPLE trial, sponsored by Gilead, and the randomized controlled Adaptive Covid-19 Treatment Trial, sponsored by the National Institute of Allergy and Infectious Diseases, show that remdesivir may accelerate recovery rates among patients with advanced Covid-19. The drug’s modest effects are a far cry from the strong antiviral activity it demonstrated in preclinical primate models of coronavirus (both MERS and SARS-CoV-2). Yet that has been enough for the Food and Drug Administration to grant emergency use authorization for remdesivir and for the Japanese Ministry of Health, Labour, and Welfare to approve it for the treatment of Covid-19.
As chemists, we are troubled by the challenges to mass producing remdesivir. We aren’t alone. On the day that results from the two trials emerged, Gilead CEO Daniel O’Day praised the chemists behind the drug, saying he is “proud of the team because this is a complicated chemical process. It takes many, many steps.”
But does it really have to be that complicated? O’Day’s admission is interesting given that Gilead has another compound in its pipeline that is easier to make, has been shown to be effective against coronavirus in animal models, and is potentially as effective as remdesivir, if not more so….
Thinking with Dean Baker:
There is reason to wonder whether there is a Gilead drug other than remdesivir that could be as or more effective and much simpler to produce. The problem being that the possible alternative drug has less remaining patent protection and is of less interest to Gilead.
anne:
Gilead’s remdesivir was initially declared an orphan drug which gives it a special status of being a drug to treat rare diseases (I will keep this simple as you probably already know this). The advantages to being declared an orphan drug are tax incentives, longer exclusivity for patent and marketing rights, research subsidies, and creating a government-run enterprise to engage in research and development. ~50% of R&D and startup are tax deductible. When demand such as what has been caused by the Pandemic increases, Pharma can cover costs in 5 years (WHO) through risk-adjusted sales. Gilead would rather have the latter that the orphan drug moniker.
In other words there, is money to be made in remdesivir. Their costs of production already covered by prior sales. It would make sense to go with the less complicated process of the GS-441524. I do not think there is any reason for Dean or anyone to wonder why Gilead is doing remdesivir. Its for the money.
Nice comment
Thank you, Run
As for the promising Chinese vaccine, development is by a Chinese team that previously produced a SARS vaccine. Chen Wei, the team leader, is a biology professor from the Academy of Military Medical Sciences and a member of the Chinese Academy of Engineering. The Chinese vaccine will be tested in several countries working with WHO scientists. A successful vaccine will be public.
anne:
I have some issues with Gilead also. They are setting themselves up. I am not sure what the recently passed Cures Act may do for them also. Been following the HCQ issues mostly.
Isn’t this the same Gilead that bought the cure for Hep-C and proceeded to sell a treatment that costs $200 to manufacture for $100,000 — take it or leave it? Together with other pharma companies and their copy cats Gilead and friends want $250 billion over 20 patent run down years NOT to wipe out Hep-C in one year.
With remdesivir I thought that Gilead would be shamed during this pandemic from gouging — might even have a little morals about it. Guessed wrong on both quarters.
Denis:
ICER suggested the price could be $50,000 for the required dosage. https://www.fiercepharma.com/pharma/gilead-to-start-selling-remdesivir-coming-weeks-expects-multi-year-commercial-opportunity Instead, Cilead will offer it at an ~$5,000.
I tend to try enjoying themed video evenings around holidays. Usually favor re-watching favorite “War is Hell” movies for Memorial Day weekend. But this year we watched this genuinely interesting feature: https://www.imdb.com/title/tt6018306/?ref_=nv_sr_srsg_0
“Last Flag Flying” features Steve Carell, Bryan Cranston, and Laurence Fishburne as three Vietnam era vets who re-unite to bury a dead son. Not one of Richard Linklater’s best known films but it will be added to a list of favorite movies for this holiday. Thoughtful, interesting and well done. It made me think about patriotism and service in ways I hadn’t considered before. Highest recommendation.