Virus World

The first-of-its-kind treatment, Paxlovid, has been found to be highly protective against severe illness. It could be available within a few days.  The Food and Drug Administration on Wednesday authorized the first pill for Covid-19, offering a highly effective defense against severe illness that will arrive as the country endures another major surge of the pandemic. The drug, developed by Pfizer and known as Paxlovid, is authorized for Covid patients age 12 and over who are vulnerable to becoming severely ill because they are older or have medical conditions such as obesity or diabetes. Tens of millions of Americans — including both vaccinated and unvaccinated people — will be eligible if they get infected with the virus. The treatment could be available within a few days. Pfizer’s laboratory studies indicate that its pills are likely to work against the Omicron variant, which has rapidly become the dominant form of new cases in the United States. A clinical trial indicated that Paxlovid is highly effective when taken soon after people start feeling sick. In a final analysis of a key study conducted while the Delta variant was surging, Pfizer’s drug reduced the risk of hospitalization or death by 88 percent when given to high-risk unvaccinated adults within five days of the start of their symptoms. Paxlovid appears to be substantially more effective than a similar antiviral pill from Merck, known as molnupiravir, that is still awaiting authorization by the F.D.A. In a clinical trial, Merck’s drug reduced risk of hospitalization and death for high-risk patients by 30 percent.

The European Union drugs regulator has recommended granting Moderna's Covid-19 vaccine a conditional marketing authorization, a move that will soon pave the way for the drug to become the second coronavirus vaccine to be distributed in the bloc.  Following the recommendation by the European Medicines Agency (EMA), the shot now must be formally authorized by the European Commission, which is expected to do so quickly. On Wednesday, the European Parliament Committee on Environment, Public Health and Food Safety said on Twitter that they are "expected to follow the (EMA) recommendation and grant the authorization shortly after which the roll-out of the vaccine in the EU can begin. "Emer Cooke, EMA executive director, said on Wednesday that "this vaccine provides us with another tool to overcome the current emergency."  "It is a testament to the efforts and commitment of all involved that we have this second positive vaccine recommendation just short of a year since the pandemic was declared by WHO," she said. Ursula von der Leyen, president of the European Commission, said in a tweet that the EMA had found that the Moderna vaccine is "safe and effective" and that their decision is "Good news for our efforts to bring more #COVID19 vaccines to Europeans!" "Now we are working at full speed to approve it & make it available in the EU," she said. The EU has secured the purchase of up to 160 million doses of the Moderna vaccine -- enough to vaccinate 80 million people of its 448 million citizens -- as part of a joint vaccine strategy aimed to ensure equitable access across the bloc.  It has also purchased up to 300 million doses of the Pfizer/BioNTech vaccine, which was authorized for use on December 21 and rolled out to all EU countries days later.

The move is meant to fast-track national vaccination drives.  The World Health Organization on Thursday listed the Pfizer/BioNTech COVID-19 vaccine for emergency use, making it the first to receive such status since the pandemic began. The WHO Emergency Use Listing opens the door for countries to fast-track their own regulatory approval to import and administer the Pfizer/BioNTech vaccine.The objective of the procedure, the organization said, is to make medical products like vaccines available as rapidly as possible to address public health emergencies while adhering to stringent safety and quality checks.  The review of the Pfizer/BioNTech vaccine found that it met WHO criteria for safety and efficacy, and that the benefits of using the vaccine to address COVID-19 offset potential risks. The United Kingdom was the first Western country to authorize Pfizer/BioNTech's vaccine.

The European Medicines Authority (EMA) will most likely not be able to approve the COVID-19 vaccine developed by drug maker AstraZeneca and the University of Oxford in January, the watchdog's Deputy Executive Director Noel Wathion said. 

AMSTERDAM (Reuters) - The European Medicines Authority (EMA) will most likely not be able to approve the COVID-19 vaccine developed by drug maker AstraZeneca and the University of Oxford in January, the watchdog’s Deputy Executive Director Noel Wathion said. “They have not even filed an application with us yet”, Wathion said in an interview with Belgian newspaper Het Nieuwsblad published on Tuesday. European regulators have only received some information about the vaccine, Wathion said. “Not even enough to warrant a conditional marketing licence”, he said. “We need additional data about the quality of the vaccine. And after that, the company has to formally apply.” This made it “improbable” that an approval could already be granted next month, Wathion said. The EMA could not be reached for comment.  AstraZeneca told Reuters last week that its COVID-19 vaccine should be effective against the new coronavirus variant, adding that studies were under way to fully probe the impact of the mutation. It has submitted a full data package about its vaccine to the British medicines regulator, British health minister Matt Hancock said.

The positive review most likely ensures that the Food and Drug Administration will grant emergency authorization to a second coronavirus vaccine this week for millions of Americans. The coronavirus vaccine made by Moderna is highly protective, according to new data released on Tuesday, setting the stage for its emergency authorization this week by federal regulators and the start of its distribution across the country. The Food and Drug Administration intends to authorize emergency use of the vaccine on Friday, people familiar with the agency’s plans said. The decision would give millions of Americans access to a second coronavirus vaccine beginning as early as Monday. The Pfizer-BioNTech vaccine, cleared last week, was the first to be authorized. “This is great news, as this now brings us to two products with high levels of efficacy,” said Rupali Limaye, an associate scientist at Johns Hopkins Bloomberg School of Public Health. The review by the F.D.A. confirms Moderna’s earlier assessment that its vaccine had an efficacy rate of 94.1 percent in a trial of 30,000 people. Side effects — including fever, headache and fatigue — were common and unpleasant, but not dangerous, the agency found.

The F.D.A. said its analysis “supported a favorable safety profile, with no specific safety concerns identified that would preclude issuance of an emergency use authorization.” The success of Moderna’s vaccine has become all the more critical to fighting the pandemic as other vaccine efforts have faltered. The hopeful news arrives at a time of record-setting numbers of coronavirus cases that are overwhelming hospitals and of an ever-increasing death toll, which reached a bleak milestone of 300,000 on Monday. The data release is the first step of a public review process that will include a daylong meeting on Thursday by an independent advisory panel of experts. They will hear from Moderna, F.D.A. scientists and the public before voting on whether to recommend authorization. The panel is expected to vote yes, and the F.D.A. generally follows the experts’ recommendations.  Distribution of about six million doses could then begin next week, significantly adding to the millions of doses already being shipped by Pfizer and BioNTech. Health care workers received the first shots on Monday of that vaccine, which has an efficacy rate of 95 percent. Emergency authorization is not the same as full approval. It allows an experimental vaccine to be used if there is evidence that its potential benefits outweigh its risks, while more data is collected to apply for full approval.

Dr. Barry R. Bloom, a professor of public health at Harvard, said the results from Moderna and Pfizer were “extraordinarily comparable.” “The good news is they both did everything they were supposed to do,” he said. Based on the data, Moderna’s vaccine may be slightly less effective in people 65 and older than Pfizer-BioNTech’s. “But it’s hard to tell,” he said. Compared with the Pfizer-BioNTech vaccine, Moderna’s was more likely to cause headaches, sore arms and related side effects, Dr. Bloom noted. The vaccine rollout is one of the most ambitious in the nation’s history, but experts are uncertain how long it will take for all 330 million Americans to be inoculated, let alone return the country’s businesses, schools and everyday routines to a new normal. Last summer, the U.S. government signed deals with Moderna and Pfizer to acquire 200 million doses in the first quarter of 2021. Because both vaccines require two doses, those contracts guaranteed enough doses for 100 million people. The government announced last week that it had purchased another 100 million doses from Moderna for the second quarter, increasing the number to 150 million who can be vaccinated.  Both vaccines will be provided free of charge. Because Moderna’s vaccine requires less extreme cold storage than the Pfizer-BioNTech product, it will be easier to ship, store and handle...

Data evaluated by FDA scientists available at:

https://www.fda.gov/advisory-committees/advisory-committee-calendar/vaccines-and-related-biological-products-advisory-committee-december-17-2020-meeting-announcement#event-materials

A rundown of the science that goes into the decision-making process and what it tells us about when results could be available. In a U.S. pandemic response dominated by missteps, the effort to develop vaccines to prevent Covid-19 has so far been a triumph. Vaccines against the coronavirus that causes the disease are now racing through giant clinical trials as a result. It’s a terrible irony, then, that the Trump administration’s statements have resulted in an erosion of public trust, with the percent of Americans who tell pollsters they would take a Covid-19 vaccine dropping and experts worrying the president could compel the Food and Drug Administration to approve a vaccine before one is ready. (Spoiler: No vaccine will likely be ready by Election Day.)  “When the the president comes out and says, ‘by a very special day, we might have a vaccine,’ the whole thing blows up,” Ashish Jha, the dean of the Brown School of Public Health, said at a session focused on Covid-19 at the STAT Health Tech Summit. “In some ways, we’ve got to get the politicians to shut up and let the scientists talk about this and drive this process.”  The process of deciding when a vaccine appears to be safe and effective isn’t as straightforward as the general public might believe. But it’s important to understand it if we are to have confidence in these critical tools for helping to curb the pandemic. Here, then, is a rundown of the science that goes into the decision-making process, what it tells us about when results could realistically be available, and when vaccines could start to be administered. This story is based on interviews as well as on documents the drug makers have released detailing their clinical trial plans. 

When will vaccine makers have enough data?

A clinical trial is typically sponsored by a company making a vaccine candidate or an academic institution, or a partnership of both. But it is actually monitored by what is known as a data and safety monitoring board, or DSMB, a group of independent experts hired to make sure volunteers in the study are safe. In many studies, the DSMB has the ability to recommend stopping a study not only if a treatment is unsafe, but also if it is so clearly effective that continuing just wouldn’t be ethical.  In the case of the vaccine trials, the studies being run by Moderna, AstraZeneca, and Johnson & Johnson with the National Institutes of Health share a common DSMB. The study being run by Pfizer and its partner BioNTech has its own. The DSMBs will conduct what’s called an interim analysis after a certain number of people have been infected with Covid-19 and shown symptoms. Each of these cases is considered an “event,” and each vaccine maker has set a different number of events as a threshold to conduct an interim analysis as part of their trial protocols. The study being run by Pfizer and its partner BioNTech, frontrunners in the race for a vaccine, is conducting its first interim analysis after 32 events, and would consider the vaccine effective if 26 people in the placebo group and six in its vaccine group had Covid. A study of Moderna’s vaccine, another frontrunner, is waiting until there are 53 cases of Covid. In the case of Pfizer and BioNTech, an interim analysis could happen in October.  Should a vaccine be approved, potentially for millions of people, after its efficacy has been shown based on 32 cases of Covid-19? 

Some experts say no. Eric Topol, the director of the Scripps Research Translational Institute, has been fervently saying that all the trials should continue beyond even their designed ends — when there are about 150 cases of Covid — saying that even the 150 number “may make statistical sense, but it defies common sense.” This could be particularly true if efficacy is limited, given that all the vaccines frequently cause side effects like fever. Others say that while making a decision based on an interim analysis is fine, the first Pfizer analysis, in particular, seems to set a relatively low bar for efficacy given the small number of events. The numbers are in line with past vaccine studies. Prevnar 13 was approved to prevent pneumonia in adults based on a study of 84,000 people that detected 139 cases of pneumonia, 90 of them in the placebo group.  But there’s also a precedent for keeping such studies going to collect more safety data. Researchers studying RotaTeq, a vaccine to prevent a virus that causes childhood diarrhea, collected data from 70,000 patients to rule out a potential side effect which had been seen with a previous vaccine....

The UK Medicines and Healthcare Products Regulatory Agency said Thursday it had authorized Merck and Ridgeback Biotherapeutics' oral antiviral, molnupiravir, to treat mild-to-moderate Covid-19 in adults at risk for severe illness. It is the world's first oral antiviral to be authorized anywhere for the treatment of Covid-19. The drug comes in capsule form and will be known as Lagevrio. The companies have sought US Food and Drug Administration emergency use authorization for the drug, and the FDA said it will convene its Antimicrobial Drugs Advisory Committee on November 30 to discuss molnupiravir's ability to treat mild-to-moderate Covid-19 in adults who are at high risk for severe disease, including hospitalization or death. Merck and Ridgeback also say the European Medicines Agency has initiated a rolling review of its marketing application.  Merck announced last month that the capsule reduced the risk of hospitalization or death from Covid-19 by half. "At the interim analysis, molnupiravir reduced the risk of hospitalization or death by approximately 50%; 7.3% of patients who received molnupiravir were either hospitalized or died through Day 29 following randomization (28/385), compared with 14.1% of placebo treated patients (53,377)," the company said in a news release in October. "Through Day 29, no deaths were reported in patients who received molnupiravir, as compared to 8 deaths in patients who received placebo." The data has not yet been peer-reviewed or published, but spurred excitement about a potentially easy, accessible treatment for Covid-19.

It aims to inoculate some 300m people this year in one of the world's largest vaccination campaigns. The drugs regulatory authority gave the green light to the jabs developed by AstraZeneca with Oxford University and by local firm Bharat Biotech. Prime Minister Narendra Modi called it "a decisive turning point". India plans to inoculate some 300 million people on a priority list this year. It has recorded the second-highest number of infections in the world, with more than 10.3 million confirmed cases to date. Nearly 150,000 people have died. On Saturday India held nationwide drills to prepare more than 90,000 health care workers to administer vaccines across the country, which has a population of 1.3 billion people.  The Drugs Controller General of India said both manufacturers had submitted data showing their vaccines were safe to use. However, opposition politicians and some doctors have criticised a lack of transparency in the approval process.

The first doses are due to be given on Monday, amid concern over rising coronavirus cases.  The UK has ordered 100 million doses - enough to vaccinate 50 million people. This would cover the entire population when combined with the full order of the Pfizer-BioNTech jab, Health Secretary Matt Hancock said. It comes as millions more people in England are expected to be the toughest tier four restrictions. Vaccination centres will now start inviting patients to come and get the jab from next week. Priority groups for immunisation have already been identified, starting with care home residents, the over-80s, and health and care workers. Eventually all over 50s and younger adults with health conditions will be offered a jab in the first phase of rollout - more than 25 million people in total. It is hoped that about two million patients a week could soon be vaccinated with two vaccines now approved.

In a landmark collective undertaking, the bloc is poised to start distributing shots to all 27 member nations and their 410 million citizens.  From Stockholm to Athens and from Lisbon to Warsaw, European Union governments are gearing up to receive a coronavirus vaccine later this week, even as cases keep rising in some parts of the continent. The bloc formally approved the Pfizer-BioNTech vaccine on Monday, setting off a logistical marathon the likes of which most of the authorities in the region have not had to contend with before. The operation to buy, approve and distribute the shots across the European Union has been complex and politically charged, and the stakes could not be higher. The pandemic’s second wave is still raging in parts of the region, most Europeans are spending the holidays in some type of lockdown, and the bloc’s economies are in tatters. To further complicate matters, a highly contagious variant in England led many European countries over the weekend to block travelers from Britain, although scientists say it has already reached the continent. If the vaccine mission is successful, it may bolster the credentials of the European Union, establishing its administration as a real force with executive powers and capabilities that can take on important tasks on behalf of its members. If not, the failure may spread acrimony and disaffection.

The European Medicines Agency, the bloc’s drug authority, gave its approval on Monday, after coming under intense scrutiny for the pace at which it reviewed the Pfizer-BioNTech vaccine. Britain granted the vaccine emergency approval weeks ago and then started rolling out its inoculation program, with the United States following not far behind. In the end, the European agency decided to speed up the process, moving forward an approval meeting that had been set for Dec. 29. The United States has also approved a vaccine from Moderna, but the European agency will not address the application for authorization of that company’s shots until Jan. 6. The agency’s authorization for the Pfizer-BioNTech vaccine was followed a few hours later by the final step, when the European Commission, the executive arm of the European Union,gave its approval, giving the green light for Pfizer to start distributing vaccines across the region.  “As we have promised, this vaccine will be available for all European countries at the same time, under the same conditions,” said Ursula von der Leyen, the European Commission president. “Let me say how proud I am that the first Covid vaccine available in Europe is a true product of the European innovation.”

The UK is the first country to approve the Pfizer vaccine - with 800,000 doses due to arrive in the coming days. Britain's medicines regulator, the MHRA, says the jab, which offers up to 95% protection against Covid-19 illness, is safe to be rolled ou. The first doses are already on their way to the UK, with 800,000 due in the coming days, Pfizer said Health Secretary Matt Hancock said the NHS will contact people about jabs. Elderly people in care homes and care home staff have been placed top of the priority list, followed by over-80s and health and care staff. But because hospitals already have the facilities to store the vaccine at -70C, as required, the very first vaccinations are likely to take place there - for care home staff, NHS staff and patients - so none of the vaccine is wasted. The Pfizer/BioNTech jab is the fastest vaccine to go from concept to reality, taking only 10 months to follow the same steps that normally span 10 years. The UK has already ordered 40 million doses of the jab - enough to vaccinate 20 million people. The doses will be rolled out as quickly as they can be made by Pfizer in Belgium, Mr Hancock said, with the first load next week and then "several millions" throughout December.

Scottish First Minister Nicola Sturgeon said the first people in Scotland will be immunised on Tuesday. The bulk of the rollout will be next year, Mr Hancock said, adding: "2020 has been just awful and 2021 is going to be better." While he said that the government does not yet know how many people need to be vaccinated before restrictions can start being lifted, he added: "I'm confident now, with the news today, that from spring, from Easter onwards, things are going to be better. And we're going to have a summer next year that everybody can enjoy."  Prime Minister Boris Johnson added: "It's the protection of vaccines that will ultimately allow us to reclaim our lives and get the economy moving again." The free vaccine will not be compulsory and there will be three ways of vaccinating people across the UK:

The experimental drug remdesivir has been approved to treat hospitalized patients with severe Covid-19, the US Food and Drug Administration said in a letter on Friday. Remdesivir is the first authorized therapy drug for Covid-19 in the United States, FDA Commissioner Stephen Hahn said on Friday. "This is an important clinical advance that showed a statistically significant reduction in time to recovery for patients with Covid-19 and is the first authorized therapy for Covid-19." Hahn said. The FDA issued an emergency-use authorization on Friday, saying the benefits of the drug outweigh its risks in patients. An emergency-use authorization is a lower regulatory bar than full FDA approval.

Denise Hinton, the FDA's chief scientist, said in the authorization letter that there is "no adequate, approved, and available alternative to the emergency use of remdesivir for the treatment of COVID-19." The FDA limited its authorization of the drug to adults and children with suspected or laboratory-confirmed Covid-19 and severe disease, which includes low blood oxygen levels, the need for oxygen therapy or the need for a ventilator or other intensive breathing support. Possible side effects of remdesivir include increased levels of liver enzymes -- which may be a sign of inflammation or damage to cells in the liver -- and infusion-related reactions like low blood pressure, nausea, vomiting, sweating and shivering, the FDA said....

The drug must be administered intravenously. While the optimal dosing is still unknown, Gilead Sciences, the drug's marker, recommends that patients on ventilators take the drug for 10 days and non-ventilator patients only five days. Gilead has donated the existing supply of the drug, which could cover at least 140,000 treatment courses for patients with Covid-19. "The company has set a goal of producing at least 500,000 treatment courses by October, 1 million treatment courses by December 2020 and millions more in 2021, if required," the company said in a statement on Friday...

FDA Authorization Letter (May 1, 2020):

https://www.fda.gov/media/137564/download

Gilead's Official Press Release (May 1, 2020):

https://www.gilead.com/news-and-press/press-room/press-releases/2020/5/gileads-investigational-antiviral-remdesivir-receives-us-food-and-drug-administration-emergency-use-authorization-for-the-treatment-of-covid19