FDA advisory panel only narrowly endorses Merck’s oral Covid treatment pill
An FDA advisory panel narrowly endorsed the use of Merck and Ridgeback Biotherapeutics’ oral Covid treatment pill, despite questions about the drug’s effectiveness, safety and whether it would help the virus mutate into even more dangerous variants.
The FDA’s Antimicrobial Drugs Advisory Committee voted 13 to 10 to recommend emergency authorisation of molnupiravir, an oral antiviral drug initially hailed as a potential game changer in the battle against Covid since it can be taken at home instead of at a hospital like other treatments. It’s designed to treat adults with mild to moderate symptoms of Covid-19 who are at high risk of severe disease. The 800 milligram pill is taken every 12 hours for five days after symptom onset.
Many members of the advisory committee described the vote as a difficult one, in which they had to carefully weight the risks and benefits of a drug that could help those most at risk but raised many unanswered questions.
Dr. Sankar Swaminathan, an infectious disease specialist at the University of Utah School of Medicine, voted against endorsing Merck’s medication because the efficacy was “modest at best.” Swaminathan also said he worried that the drug’s potential affect on human DNA wasn’t adequately understood.
Merck originally said the drug was more than 50% effective in preventing hospitalisations and death, but a more full set of data presented to the FDA on Tuesday noted the drug is just 30% effective.
The FDA and Merck both recommended against using the drug in children and pregnant women
The drug needs final authorisation from the FDA and Centers for Disease Control and Prevention (CDC) before it’s available to the public on an emergency basis. The FDA doesn’t have to take the panel’s advice, but it often does.
Source: CNBC news
WHO update on the new Variant of Concern, Omicron
On 26 November 2021, WHO designated the variant B.1.1.529 a variant of concern, named Omicron, on the advice of WHO’s Technical Advisory Group on Virus Evolution (TAG-VE).
Some of the more important points concerning the new variant are:
- Transmissibility: It is not yet clear whether Omicron is more transmissible (e.g., more easily spread from person to person) compared to other variants, including Delta. T
- Severity of disease: It is not yet clear whether infection with Omicron causes more severe disease compared to infections with other variants, including Delta. Preliminary data suggests that there are increasing rates of hospitalization in South Africa, but this may be due to increasing overall numbers of people becoming infected, rather than a result of specific infection with Omicron.
- Symptoms: There is currently no information to suggest that symptoms associated with Omicron are different from those from other variants. Initial reported infections were among university students—younger individuals who tend to have more mild disease—but understanding the level of severity of the Omicron variant will take days to several weeks.
- Effectiveness of prior SARS-CoV-2 infection: Preliminary evidence suggests there may be an increased risk of reinfection with Omicron (ie, people who have previously had COVID-19 could become reinfected more easily with Omicron), as compared to other variants of concern, but information is limited.
- Effectiveness of vaccines: WHO is working with technical partners to understand the potential impact of this variant on existing countermeasures, including vaccines.
- Effectiveness of current tests: The widely used PCR tests continue to detect infection, including infection with Omicron. Studies are ongoing to determine whether there is any impact on other types of tests, including rapid antigen detection tests.
- Effectiveness of current treatments: Corticosteroids and IL6 Receptor Blockers will still be effective for managing patients with severe COVID-19. Other treatments will be assessed to see if they are still as effective given the changes to parts of the virus in the Omicron variant.
Source: WHO website
Data on vaccine protection against new COVID-19 variant Omicron expected soon while a booster candidate tailored to the new variant is advanced
BioNTech SE said it expects more data on the new coronavirus variant detected in South Africa, within two weeks to help determine whether its vaccine produced with partner Pfizer Inc will have to be reworked.
Pfizer and BioNTech said that if necessary they expect to be able to ship a new vaccine tailored to the emerging variant in approximately 100 days.
Moderna Inc. said in a statement that it is working to advance a booster candidate tailored to the new variant and has also been testing a higher dose of its existing booster and to study other booster candidates designed to protect against multiple variants.
New Covid-19 variant B.1.1.529 (named omicron) detected, with potential implication yet to be understood
Scientists have detected a new Covid-19 variant called B.1.1.529 and are working to understand its potential implications. Because the variant has only recently emerged, scientists do not yet have evidence of its transmissibility or ability to evade vaccines. About 50 confirmed cases have been identified in South Africa, Hong Kong and Botswana.
B.1.1.529 has a very unusual constellation of mutations, which are worrying because they could help it evade the body’s immune response and make it more transmissible, scientists have said.
Senior scientists described B.1.1.529 as the worst variant they have seen since the start of the pandemic. It has 32 mutations in the spike protein, the part of the virus that most vaccines use to prime the immune system against Covid. That is about double the number associated with the Delta variant. Mutations in the spike protein can affect the virus’s ability to infect cells and spread, but also make it harder for immune cells to attack the pathogen.
Based on the evidence presented indicative of a detrimental change in COVID-19 epidemiology, the TAG-VE has advised WHO that this variant should be designated as a Variant of Concern (VOC), and the WHO has designated B.1.1.529 as a VOC, named Omicron.
Some further information on the new variant is provided by Dr Maria Van Kerkhove of the WHO, in this presentation (starting at 25.50 minutes in the presentation and ending at 29.05 minutes).
EMA public stakeholder meeting on vaccines and therapeutics in the EU
Here is a link to the detailed EMA public stakeholder meeting on vaccines and therapeutics in the EU of 25 November.
Status of administered COVID-19 doses across the globe
As of 25 November, 53.8% of the world population has received at least one dose of COVID-19 vaccine. 7.81 billion doses have been administered globally and 28.33 million are now administered each day.
Only 5.5% of the people in low-income countries have received at least one dose.
COVID-19 vaccines approved and in clinical trials globally
This site (link below) provides some very basic but useful information on the global progress with clinical trials for vaccines for COVID-19. You can also view information on vaccine approvals (this can be an emergency use authorisation or a conditional marketing authorisation but not a full approval) by country.
As of 25 November, the situation is as follows:
- No of approved vaccines = 24
- No of vaccines in Phase I trials = 38
- No of vaccines in Phase II trials = 57
- No of vaccines in Phase III trials = 56
Some questions about the new Covid pills from Merck and Pfizer
There has been much in the press recently about the new oral COVID-19 medicines from Merck (Lagevrio) and Pfizer (Paxlovid).
Each treatment is administered twice a day for five total days, amounting to 10 doses in total. Pfizer’s drug is co-administered with a common antiviral called ritonavir.
STAT News has published an article in which it asks some pertinent questions about these oral medicines
Source: STAT news
FDA wants 55 years to process FOIA request over vaccine data
When a group of scientists, Public Health and Medical Professionals For Transparency (PHMPT) asked the federal government (in a Freedom of Information Act request) to share the data it relied upon in licensing Pfizer’s COVID-19 vaccine, the response went beyond typical bureaucratic foot-dragging.
The FDA proposes (in court papers this week) that it should be given 55 years to review and release the trove of vaccine-related documents in response to the request. If a federal judge in Texas agrees, plaintiffs Public Health and Medical Professionals for Transparency can expect to see the full record in 2076.
FOIA law normally requires federal agencies to respond to information requests within 20 business days, but the time “will vary depending on the complexity of the request and any backlog of requests already pending at the agency,” according to the government’s central FOIA website
Justice Department lawyers representing the FDA note in court papers that the plaintiffs are seeking a huge amount of vaccine-related material – about 329,000 pages.
The plaintiffs, , a group of more than 30 professors and scientists from universities including Yale, Harvard, UCLA and Brown, filed suit in September in U.S. District Court for the Northern District of Texas, seeking expedited access to the records. They say that releasing the information could help reassure vaccine skeptics that the shot is indeed “safe and effective and, thus, increase confidence in the Pfizer vaccine.”
However, the FDA can’t simply turn the documents over wholesale. The records must be reviewed to redact “confidential business and trade secret information of Pfizer or BioNTech and personal privacy information of patients who participated in clinical trials,” wrote DOJ lawyers in a joint status report filed Monday.
The FDA proposes releasing 500 pages per month on a rolling basis, noting that the branch that would handle the review has only 10 employees and is currently processing about 400 other FOIA requests.
Plaintiffs’ lawyers argue that their request should be top priority and that the FDA should release all the material no later than March 3, 2022.
US plans to invest significant sums of money in manufacturing mRNA COVID-19 vaccines
The US in aplanning to invest billions of dollars in expanding COVID-19 vaccine manufacturing capacity and make available an additional one billion doses per year according to the White House COVID-19 coordinator Jeff Zients.
Zients said the government was preparing to offer makers of the mRNA vaccines substantial help to expand infrastructure and capacity, including facilities, equipment, staff or training.
Pfizer/BioNTech and Moderna are the only makers of mRNA vaccines, though Zients said subcontractors of those companies would also be included.
Production will start in the second half of 2022, he said.
The investment in vaccine production is part of a private-public partnership to address vaccine needs at home and around the world and to prepare for future pandemics, he said. It will be paid for with funds from the American Rescue Plan Biden signed into law in March.
Pfizer agrees to let other companies make its experimental COVID-19 pill
Pfizer Inc. has signed a deal with a U.N.-backed group to allow other manufacturers to make its experimental COVID-19 pill, a move that could make the treatment available to more than half of the world’s population.
Pfizer said it would grant a license for the antiviral pill to the Geneva-based Medicines Patent Pool, which would let generic drug companies produce the pill for use in 95 countries, making up about 53% of the world’s population.
The deal excludes some large countries that have suffered devastating coronavirus outbreaks. For example, while a Brazilian drug company could get a license to make the pill for export to other countries, the medicine could not be made generically for use in Brazil.
MSD has also recently entered into a licence agreement with Medicines Patent Pool for molnupiravir, an investigational oral antiviral COVID-19 medicine, to increase broad access in low- and middle- income countries.
Moderna offers NIH co-ownership of COVID vaccine patent amid dispute with government
The National Institutes of Health has engaged Moderna in “good faith discussions” to resolve a month long dispute over the company’s patent application that advocates say could impact global production of the shots.
Moderna is offering to share ownership of its COVID-19 vaccine patent with the U.S. government to resolve the dispute, the vaccine maker said, and would allow the Biden administration to “license the patents as they see fit.”
The company claims it had no choice under the “strict rules” of American patent law to list only its own scientists “as the inventors on these claims.”
However, aspokesperson within the NIH – said that “its own thorough review” had determined that scientists Kizzmekia Corbett, Barney Graham, and John Mascola also deserved to be named as inventors.
“Moderna has made a serious mistake here in not providing the kind of co-inventorship credit to people who played a major role in the development of the vaccine that they are now making a fair amount of money off of,” NIH Director Dr. Francis Collins told Reuters last week.
Source: CBS News
Some people testing negative for Covid-19 despite exposure may have ‘immune memory’
A study suggests some individuals clear virus rapidly due to a strong immune response from existing T-cells, meaning tests record negative results.
We all know that person who, despite their entire household catching Covid-19, has never tested positive for the disease. Now scientists have found an explanation, showing that a proportion of people experience “abortive infection” in which the virus enters the body but is cleared by the immune system’s T-cells at the earliest stage meaning that PCR and antibody tests record a negative result.
The discovery could pave the way for a new generation of vaccines targeting the T-cell response, which could produce much longer lasting immunity, scientists said.
The study intensively monitored healthcare workers for signs of infection and immune responses during the first wave of the pandemic. Despite a high risk of exposure 58 participants did not test positive for Covid-19 at any point. However, blood samples taken from these people showed they had an increase in T-cells that reacted against Covid-19, compared with samples taken before the pandemic took hold and compared with people who had not been exposed to the virus at all. They also had increases in another blood marker of viral infection.
The work suggests that a subset of people already had memory T-cells from previous infections from other seasonal coronaviruses causing common colds, which protected them from Covid-19.
The study adds to the known spectrum of possibilities after exposure to Covid-19, ranging from escaping infection entirely to severe disease.
Source: The Guardian
AstraZeneca aims to create a separate division for vaccines and antibody therapies
AstraZeneca is creating a separate division for vaccines and antibody therapies to focus on its COVID-19 shot and coronavirus treatments after a series of setbacks during the pandemic.
Reuters reported in July that the Anglo-Swedish company was exploring options for its vaccine business and expected to have greater clarity on the matter by the end of 2021.
The new division will combine research and development, manufacturing, as well as commercial and medical teams, a company spokesperson said.
The decision to set up a new business comes after a tumultuous 18 months for the drugmaker, which developed its COVID-19 vaccine in conjunction with the University of Oxford.
The creation of the vaccines division, first reported by the Financial Times, indicates AstraZeneca sees a future for its COVID-19 shot beyond the pandemic but this shouldn’t be taken as a sign that it is planning a full-scale entry into the broader vaccine market, according to Hargreaves Lansdown analyst Nicholas Hyett.
“That would require significant new research and development investment, and as yet we have no indication that this is forthcoming,” he said.
EMA and HMA update on Molnupiravir (also known as MK 4482 or Lagevrio)
The EMA and the HMA have agreed on the need for additional guidance on COVID-19 treatments in light of rising rates of infection and deaths due to COVID-19 across the EU.
While the more comprehensive rolling review is ongoing ahead of a possible application for a marketing authorisation, EMA’s CHMP will provide EU-wide recommendations in the shortest possible timeframe to help national authorities decide on possible early use of the medicine, for example, in emergency use settings.
Molnupiravir is an oral antiviral medicine developed by Merck Sharp & Dohme in collaboration with Ridgeback Biotherapeutics.
Source: EMA website
Pfizer’s claims novel Covid-19 oral antiviral treatment candidate ( PAXLOVID™) reduces risk of hospitalisation by 89% in interim analysis of Phase 2/3 study
Pfizer Inc. announced that its investigational novel COVID-19 oral antiviral candidate, PAXLOVID™, significantly reduced hospitalisation and death, based on an interim analysis of the Phase 2/3 EPIC-HR (Evaluation of Protease Inhibition for COVID-19 in High-Risk Patients) randomised, double-blind study of non-hospitalised adult patients with COVID-19, who are at high risk of progressing to severe illness.
- The scheduled interim analysis showed an 89% reduction in risk of COVID-19-related hospitalisation or death from any cause compared to placebo in patients treated within three days of symptom onset (primary endpoint)
- 0.8% of patients who received PAXLOVID™ were hospitalized through Day 28 following randomization (3/389 hospitalised with no deaths), compared to 7.0% of patients who received placebo and were hospitalised or died (27/385 hospitalized with 7 subsequent deaths). The statistical significance of these results was high (p<0.0001).
- Similar reductions in COVID-19-related hospitalisation or death were observed in patients treated within five days of symptom onset; 1.0% of patients who received PAXLOVID™ were hospitalised through Day 28 following randomization (6/607 hospitalized, with no deaths), compared to 6.7% of patients who received a placebo (41/612 hospitalised with 10 subsequent deaths), with high statistical significance (p<0.0001).
- In the overall study population through Day 28, no deaths were reported in patients who received PAXLOVID™ as compared to 10 (1.6%) deaths in patients who received placebo.
At the recommendation of an independent Data Monitoring Committee and in consultation with the U.S. FDA, Pfizer will cease further enrollment into the study due to the overwhelming efficacy demonstrated in these results and plans to submit the data as part of its ongoing rolling submission to the U.S. FDA for Emergency Use Authorisation (EUA) as soon as possible.
If approved or authorised, PAXLOVID™, which originated in Pfizer’s laboratories, would be the first oral antiviral of its kind, a specifically designed SARS-CoV-2-3CL protease inhibitor.
FDA Multilingual COVID-19 Resources
FDA provides this very useful multilingual resource on COVID-19.
Researcher blows the whistle on data integrity issues in Pfizer’s COVID-19 vaccine trial
Revelations of poor practices at a contract research company helping to carry out Pfizer’s pivotal covid-19 vaccine trial raise questions about data integrity and regulatory oversight.
For researchers who were testing Pfizer’s vaccine at several sites in Texas during autumn 202, speed may have come at the cost of data integrity and patient safety. A regional director who was employed at the research organisation Ventavia Research Group told The BMJ that the company falsified data, unblinded patients, employed inadequately trained vaccinators, and was slow to follow up on adverse events reported in Pfizer’s pivotal phase III trial.
Staff who conducted quality control checks were overwhelmed by the volume of problems they were finding. After repeatedly notifying Ventavia of these problems, the regional director, Brook Jackson, emailed a complaint to the US Food and Drug Administration (FDA). Ventavia fired her later the same day. Jackson has provided The BMJ with dozens of internal company documents, photos, audio recordings, and emails.
Source: British Medical Journal (BMJ)