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    Amgen exec: Biosims may have lagged in the U.S., but now they’re paying off

    For years, industry watchers have wondered whether the U.S. biopharma business needed a jump-start as new launches languished and brands kept their dominant market positions. But Amgen’s latest quarterly results show there’s still plenty of potential for a dedicated player. Amgen’s biosimilars—a group that includes copycats to Roche cancer blockbusters Avastin and Herceptin—generated $480 million during the third quarter, the company said Wednesday. The franchise is now running at about a $2 billion-per-year rate, about double the revenue of last year, Bernstein analyst Ronny Gal pointed out on Wednesday’s call.

    Despite the COVID-19 pandemic, the company has “done a really nice job …. establishing strong penetration into the U.S. oncology market,” Amgen’s executive vice president of commercial operations, Murdo Gordon, said on Wednesday’s call.

    After earlier biosim launches were slow to gain steam, some experts wondered whether the U.S. would be better off giving up on the money-saving promise of biosimilars. Instead, they said, the government could regulate prices directly after biologic drugs lose exclusivity. Others, such as former FDA Commissioner Scott Gottlieb, M.D., said it was too soon to call it quits.

    For his part, Gordon said it’s an “efficient market” and that “when there is a clear value on the table, healthcare systems, providers and payers are able to capitalize on it.”

    “That’s what’s driving of course the uptake of our biosimilars,” he added.

    Amgen’s situation is different from that of some companies marketing copycat biologics. The company has defended its own brands—such as white blood cell booster Neulasta—against biosimilar competition, and that effort has “positioned us well to understand how accounts are looking to purchase biosimilars,” Gordon said.

    Further, Amgen has a “very effective provider-focused commercial presence,” the exec said, meaning the same Amgen sales reps who are discussing innovative drugs with doctors are also talking about biosimilars. The company has a patient services group that helps with reimbursement and co-pay assistance, too.

    While uptake for Amgen’s oncology biosims has been stronger than the company initially expected, Gordon cautioned against making assumptions about its immunology biosimilar franchise. Amgen’s biosim to Johnson & Johnson’s Remicade has been on the market for under a year and hasn’t yet taken off. The company’s biosim to Roche’s Rituxan is set for a December decision at the FDA.

    Looking forward, Bernstein’s Gal questioned whether Amgen expects to maintain its level of biosim growth next year. Gordon said the company can “continue to capture good volume albeit at some price erosion” as new competitors launch. Still, Amgen has “a lot of headroom for growth,” Gordon said.

    Amgen’s results come several years after the first biosimilar launches in the U.S. Pfizer’s biosimilar to Remicade was among the early launches, hitting the market in October 2016 at a 15% discount to the brand. The copycat was slow to take off, and Pfizer sued J&J for “anticompetitive” contracting to protect its important brand. J&J hit back in a public statement that Pfizer wasn’t offering enough value to win business. This year, the lawsuit has been in the discovery process, according to law firm Goodwin.

    Pfizer itself generated $424 million in sales for the biosim franchise during the third quarter. Back in August, Bernstein’s Gal wrote that the biosims market is entering a “golden age” and that the companies will generate billions of dollars in revenues from the market.

    For Amgen, the biosimilar contribution helped propel the company to third-quarter revenue growth of 12% to $6.4 billion despite challenges associated with the pandemic. New immunology acquisition Otezla chipped in $538 million, while Enbrel’s quarterly haul was $1.33 billion.

    Pharma Tested by a pandemic, pharma supply chain showed resilience

    When the COVID-19 pandemic began to sweep across the U.S. this year, early fears of shortages of critical pharmaceutical supplies and life-saving drugs were quickly abated by a responsive and resilient supply chain. As the crisis unfolded and the public’s attention was focused on shortages of everyday items like toilet paper, paper towels and disinfectants, patients with critical needs for treatments that ranged from insulin to inhalers also began to fret.

    Manufacturers worried as well. Was the pharmaceutical industry prepared to meet the challenge? Particularly since—according to industry averages—between 70% to 80% of APIs (active pharmaceutical ingredients) are manufactured in China and roughly 40% to 50% of generic drugs are produced in India. On top of that were early shortages of protective equipment like face masks, face shields and gowns for front-line healthcare workers and other essential workers like associates at AmerisourceBergen’s distribution centers. AmerisourceBergen is one of the nation’s primary pharmaceutical wholesale distribution entities. The company picks, packs and ships nearly 4 million pharmaceutical and healthcare products daily and services more than 65,000 hospitals, pharmacies, physicians’ practices and clinics annually.

    “Our family and friends used to say they didn’t really understand what we did every day,” Heather Zenk, Senior Vice President for Strategic Global Sourcing at AmerisourceBergen, said. “Now supply chain is something we talk about around the kitchen table.”

    The immediate response from the company was to ensure that its front-line associates—primarily distribution center associates, patient-facing nurses and pharmacy staff—were monitored for health and provided the protective equipment they needed. If anyone across AmerisourceBergen could work from home, they were asked to do so.

    Concurrent with those actions was a program to support front-line associates that provided day-care needs and paid time off for employees who either needed to quarantine themselves or their families. Additional steps included daily temperature checks, constant sanitization of warehouse sites that now utilize ultraviolet robots, and an app with Centers for Disease Control questions to help monitor associates’ health.

    Having a good business continuity plan

    “What served us, our partners and customers well was our ability to be resilient and have a nimble business continuity plan,” Erin Horvath, President of AmerisourceBergen’s Distribution Services, said. “We were able to handle certain circumstances like having to close a distribution center for a short period of time, divert product orders to another facility and still meet the needs of our customers.”

    An example was the company’s closure for several days of its Newburgh, N.Y. distribution facility at the height of that state’s COVID-19 outbreak last spring although the site’s positive tests for the virus were very low.

    “We saw associates were getting uneasy about coming in and we wanted them to know we cared and wanted to protect them, so we decided to close that center,” Horvath said. “We could take that action because we knew we had the network to support customers by servicing them through our other distribution centers.”

    With a network of 33 human health and specialty distribution centers and 19 animal health distribution centers and depots nationwide and about 4,000 associates manning them, AmerisourceBergen was able to implement a robust business plan with a long track record of responding to other natural disasters like hurricanes, earthquakes and wildfires. Only, instead of day and weeks of response, the pandemic has persisted for months and will likely continue through the first half of next year.

    That history of successful crisis response is supported by close partnerships with a variety of government agencies, as well as its relationship with Healthcare Ready, a Washington, D.C.-based nonprofit focused on supporting the healthcare supply chain by collaborating with government entities and the private industry sector.

    Such collaboration between the private sector, government agencies and with non-profit health organizations will play an integral part as vaccines developed to fight COVID-19 start to become available in the coming months and year.

    Partnerships across the board will be a key part when it comes to distributing and administering those vaccines, and both Horvath and Zenk agree that the centerpiece to a successful outcome has and will continue to be open and transparent communication.

    “Early on, we knew to invest the time in that kind of communication so that everyone wasn’t fighting the same battle for resources,” Zenk said. “Because of that, we were able to respond to customers very honestly and quickly. We saw hospital customers changing therapies as they learned more about how to treat the virus; we were able to routinely check in with them on the therapeutics they needed most and start supporting them right away.”

    Zenk also points out that with the attention mostly focused on the pandemic response this year there were about 20 launches of new oncological treatments. A clear indication that despite the immediate crisis, innovation in the pharmaceutical industry continues, and that innovation needed to be distributed to patients in the same manner they were accustomed to getting under normal circumstances.

    Preparing for a vaccine rollout

    As vaccines become available, they will initially be allocated to those most at risk like front-line health-care workers, essential workers and populations such as the elderly and people with co-morbidities. When a nationwide vaccine program is rolled out and begins to reach critical mass deeper into 2021 it will likely involve multiple manufacturers offering multiple treatments, all of which will need the strength of the full national supply chain and distribution system.

    “Something of this scale has never been undertaken before,” Horvath said. “We are talking about a vaccine that includes two doses and requires frozen and ultra-frozen storage and transportation capabilities—and will need to be available to the entire population of the United States.”

    AmerisourceBergen has extensive experience in managing ultra-low temperature products and is standing ready to support the vaccine distribution effort when needed, both Horvath and Zenk said.

    Clearly it will involve an enormous effort by the government and private industry and will require independent neighborhood pharmacies, large retail pharmacies and physicians to have a voice in the project.

    “We have invested hundreds of millions of dollars in our technology and in our distribution network in the last 10 years and in the past months we’ve seen that those investments pay off. They have given us the agility and resilience to do things in a very quick manner,” said Horvath.

    “One of the great things I’ve observed during this time is how the national healthcare system has been working more like a community,” Zenk added. “A hospital in one region might say they are doing okay, but then ask us to make sure another hospital in another area that might be a hot zone gets what they need.”

    Eli Lilly may face FDA warning letter after recent inspection at COVID-19 antibody plant found more issues: report

    Eli Lilly’s chances at an emergency use authorization for a COVID-19 antibody took a big hit after a major trial was stopped for safety concerns and the FDA flagged problems at a manufacturing site producing the therapy. Now, the FDA is back for more, and it could spell even bigger problems. Lilly could face an FDA warning letter after a follow-up inspection at the plant that showed “a major failure of quality assurance,” sources told Bloomberg. Located in Branchburg, New Jersey, the site is manufacturing Lilly’s COVID-19 antibody LY-CoV555, among other drugs.

    An FDA warning letter, which signals continuing deficiencies at a drug manufacturing plant, would escalate the current “official action indicated” notice Lilly received for a previous FDA inspection at the site in November 2019.

    In that notice, the FDA cited Lilly on two counts of inadequate “control of computer systems,” the drugmaker confirmed last week. The agency cited the plant for improperly deleting data on its manufacturing processes and failing to review quality-control audits, sources told Reuters.

    Despite that earlier citation, FDA inspectors again found problems at the plant in August, Bloomberg reported, and is asking the agency to “take action.” The Branchburg site is one of five that produce the antibody, Lilly said in a Tuesday statement, and the FDA has yet to issue a warning letter to the drugmaker.

    In response to the FDA’s findings in November, Lilly has added staff at the Branchburg site and hired an external consultant to review its data handling, the company said.

    While Lilly maintains that the shortfalls flagged by the FDA haven’t affected the quality of its antibody, which the agency is reviewing for an emergency authorization, sources painted a different picture for Bloomberg.

    Compliance officers conveyed one incident in which a Lilly employee used the wrong material in a “crucial” purification process, Bloomberg said. Employees also reportedly retested samples for impurities to get back a positive result and denied FDA investigators’ requests to review human resources documents related to potential data handling citations.

    A Lilly spokesman refused to comment in an email on the specific allegations in the Bloomberg report, saying the company was “not in receipt of any of the documents referenced by Bloomberg and thus cannot confirm their authenticity.”

    The Branchburg site also produces migraine med Emgality, and Lilly has requested FDA authorization to produce GLP-1 diabetes med Trulicity on-site as well, Bloomberg said.

    Potential quality issues for Lilly’s antibody come as an ill omen after the National Institutes for Health halted a phase 3 study of the therapy earlier this month on safety concerns.

    The trial’s independent data safety monitoring board recommended the company pause enrollment, a Lilly spokesperson told CNBC in an email, adding, “Lilly is supportive of the decision by the independent DSMB to cautiously ensure the safety of the patients participating in this study.”

    The trial halt came just days after Lilly asked the FDA to clear LY-CoV555 for emergency use based on phase 2 data showing it cut the rate of hospitalizations in patients recently diagnosed with mild to moderate COVID-19. However, two of the three doses tested in the study failed to beat placebo in terms of reducing viral load by the 11-day mark.

    Does Roche’s Actemra work in COVID-19? New studies once again paint mixed picture

    Roche’s arthritis drug Actemra was one of the earliest-identified COVID-19 treatment prospects. But the latest clinical studies have yielded mixed data—and seemingly contradictory results. A large observational study that looked at 3,924 critically ill COVID-19 patients admitted to intensive care units across top U.S. institutions linked Actemra treatment to a 29% reduction in the risk of death after a median follow-up of 27 days, according to results published in JAMA Internal Medicine.

    Overall, an estimated 27.5% of patients who got Actemra within two days of ICU admission would die after 30 days, versus 37.1% for those who didn’t receive it. The beneficial effect was most pronounced in patients who had a more rapid disease trajectory and were admitted to the ICU within three days of symptom onset, the study finds.

    Dysregulated inflammation plays an important role in COVID-19 disease progression. As the body fights the coronavirus, it may release too many inflammatory agents that may lead to organ failure or death. IL-6, which Actemra targets, is among those molecules found to be elevated in this cytokine release syndrome.

    However, controlling IL-6 with Actemra hasn’t consistently translated into clear clinical benefits as scientists had hoped.

    In a randomized clinical trial of 126 severe COVID-19 patients in Italy, investigators found no evidence of an Actemra-related improvement in disease progression—namely, the lungs’ ability to exchange air, ICU admission or death, according to results also published Tuesday in JAMA Internal Medicine. Specifically, 17 patients (28.3%) in the Actemra arm and 17 (27.0%) in the standard care group showed clinical worsening in 14 days.

    Then, to further complicate the situation, a randomized clinical trial, which enrolled hospitalized patients in France with moderate-to-severe COVID-19 pneumonia, also found mixed results for Actemra.

    Patients on the Roche drug were 42% less likely to require ventilation or die by day 14, according to a third study that appeared Tuesday in JAMA Internal Medicine. However, on the study’s other co-primary endpoint, the drug didn’t cut the risk of disease progression to a prespecified WHO clinical status benchmark by day 4.

    The three studies add to a growing body of evidence that has yet to reach a conclusion about Actemra’s role in COVID-19. They have their limitations, which makes interpreting their findings difficult. For example, there are potentially important differences in treatment groups at baseline in the U.S. observational study, Jonathan Parr of the University of North Carolina at Chapel Hill pointed out in an editorial that ran alongside the papers. Some of the patients in the Italian study who were not assigned to the experimental group actually got Actemra as their disease worsened, he noted.

    He also questioned the significance of the French finding that Actemra may improve outcomes at 14 days, given mixed 28-day findings from two Roche-sponsored trials. The Covacta study showed Actemra couldn’t significantly improve clinical status or prevent death compared with placebo. But in the Empacta trial, which primarily enrolled patients from minority racial and ethnic groups, the drug led to a major reduction of mechanical ventilation or death by day 28, though the death rate difference was not statistically significant.

    Parr said he would wait for detailed, peer-reviewed results from those two studies and others. The Actemra arm in the U.K.’s massive Recovery trial “will better define [Actemra’s] role in COVID-19 management,” he said. That study recently found low-cost steroid dexamethasone could reduce the death rate in hospitalized patients.

    “For now, however, findings from the randomized trials described herein do not support routine [Actemra] use in COVID-19,” Parr said.

    Pfizer CEO, facing pushback, shifts COVID-19 vaccine timeline to late November

    For months, Pfizer CEO Albert Bourla had maintained that the company would know this month whether its BioNTech-shared COVID-19 vaccine works. But top scientists pushed back, the FDA released detailed guidelines and critics grew increasingly louder.

    Now, finding himself alone in the biopharma world with that bullish estimate, the Big Pharma chief is changing his tone.

    Pfizer won’t apply for FDA emergency use authorization before the third week of November, Bourla wrote in an open letter on Friday.

    What about October? That’s when the company might know whether the vaccine, dubbed BNT162, is effective, but the company still needs to gather enough safety data for an application, Bourla explained.

    That’s a clear shift from Bourla’s previous comments, which constantly featured “October” as the key word—at a time when President Donald Trump was touting a vaccine before the Nov. 3 election, and mentioning Pfizer by name.

    “Right now, our model, our best case, predicts that we will have an answer by the end of October,” Bourla previously said on the “Today” show. During a digital event in September, he also said the company expected initial results in late October and would seek FDA authorization as soon as possible. In October, “the truth will be revealed,” was what he told The Washington Post.

    That October timeline sounded even more aggressive when Moderna CEO Stephane Bancel, known for touting ambitious goals, said his company’s shot, which was the first in the U.S. to move into clinical testing, likely wouldn’t have data until November.

    Then, in late September, more than 60 researchers and bioethicists urged Pfizer to wait until late November at earliest to file its vaccine for FDA review, arguing a submission before accruing at least two months of safety data would “severely erode public trust and set back efforts to achieve widespread vaccination.”

    For an emergency use application, the FDA is requiring at least two months of safety data on half of the trial participants after their final vaccine doses, according to a guidance document released last week.

    To understand the vaccine’s efficacy—that is, whether it can protect individuals from COVID-19—a certain number of COVID-19 cases in the phase 3 trial need to be counted before investigators can compare the effectiveness of the vaccine with placebo. That means the data may come earlier—by October—if infections come quickly, Bourla explained in the open letter.

    But effectiveness is only one of three metrics Pfizer will use for applying its vaccine for public use, he added. “Safety is, and will remain, our number one priority, and we will continue monitoring and reporting safety data for all trial participants for two years,” he said.

    What’s more, the company will also gather manufacturing data to demonstrate “the quality and consistency of the vaccine that will be produced,” Bourla said. And that information will be ready before the safety readout, he said.

    Despite his previous timeline falling in line with Trump’s, Bourla has said Pfizer is only “moving at the speed of science,” not politics. “In this hyper-partisan year, there are some who would like us to move more quickly and others who argue for delay,” he wrote in another open letter earlier this month. “Neither of those options are acceptable to me.”

    Johnson & Johnson announces European Commission approval of agreement to supply 200 million doses of Janssen’s COVID-19 vaccine candidate

    Johnson & Johnson (NYSE: JNJ) (the Company) announced the European Commission (EC), acting on behalf of the European Union (EU) Member States, has approved an Advance Purchase Agreement in which the Janssen Pharmaceutical Companies will supply 200 million doses of its COVID-19 vaccine candidate to EU Member States following approval or authorization from regulators. The EU Member States also have the option to secure up to 200 million additional doses.

    “The COVID-19 pandemic continues to threaten communities worldwide and we have a responsibility to ensure access to our COVID-19 vaccine as soon as we can. We appreciate the Commission’s and the Member States’ support for our COVID-19 vaccine candidate and development efforts,” said Paul Stoffels, M.D., Vice Chairman of the Executive Committee and Chief Scientific Officer, Johnson & Johnson.

    This contract follows the conclusion of exploratory talks with the EC. The Company is in ongoing discussions with other stakeholders, including national governments and global organizations, as part of its efforts to meet its commitment to make its vaccine candidate accessible globally, provided the vaccine has a good safety profile, is efficacious and receives approval or authorization from regulators.

    Separate to the agreement with the EC, as part of the Company’s larger commitment to respond to the COVID-19 pandemic, Johnson & Johnson has also announced plans to allocate up to 500 million vaccine doses toward international efforts to ensure access for lower income countries, with delivery beginning mid next year following approval or authorization from regulators. Recognizing the unique global demand for COVID-19 vaccines, we are working tirelessly to further expand the number of available doses.

    Johnson & Johnson is developing and testing Janssen’s COVID-19 vaccine candidate in accordance with its usual rigorous ethical standards of safety and sound scientific principles. The Company is evaluating a single-dose regimen in its large-scale, pivotal, multi-country Phase 3 trial (ENSEMBLE) that started in September. A second Phase 3 study with a two-dose regimen is planned to start later this year. The Company is committed to transparency and sharing information related to the Phase 3 ENSEMBLE study – including the study protocol.

    Janssen’s investigational COVID-19 vaccine leverages Janssen’s AdVac® technology. The same technology was used to develop Janssen’s EC-approved Ebola vaccine regimen and is the basis for its HIV, RSV and Zika vaccine candidates. To date, more than 100,000 individuals have been vaccinated with a Janssen AdVac®-based vaccine. Based on our understanding of the stability of our vaccines, we anticipate our COVID-19 vaccine candidate to be compatible with standard distribution channels without the need for new distribution infrastructure.

    About Johnson & Johnson

    At Johnson & Johnson, we believe good health is the foundation of vibrant lives, thriving communities and forward progress. That’s why for more than 130 years, we have aimed to keep people well at every age and every stage of life. Today, as the world’s largest and most broadly-based healthcare company, we are committed to using our reach and size for good. We strive to improve access and affordability, create healthier communities, and put a healthy mind, body and environment within reach of everyone, everywhere. We are blending our heart, science and ingenuity to profoundly change the trajectory of health for humanity.

    About the Janssen Pharmaceutical Companies

    At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.

    AstraZeneca puts a time limit on its COVID-19 ‘no-profit’ pledge: report

    As more than a half-dozen pharma companies race to develop vaccines to fight COVID-19, AstraZeneca has stood out for its pledge that it won’t try to profit off its shot until after the pandemic ends. Now, the company may be walking back that vow a bit. AstraZeneca could declare the pandemic over as early as July 2021, according to a memo of understanding obtained by the Financial Times between the company and a Brazilian manufacturer. The pandemic period might be extended if AstraZeneca determines it’s not over, the memo said.

    How will AstraZeneca make that determination? The company isn’t long on details. It will “seek expert guidance, including from global organizations,” a company spokesperson said.

    The spokesperson did not confirm the existence of the memo, but said in a statement that the company’s approach is to treat the COVID-19 vaccine “as a response to a global public health emergency, not a commercial opportunity.”

    In July, AstraZeneca told Fierce Pharma it would price the vaccine “to support broad and equitable access around the world,” and the company’s executive vice president of biopharmaceuticals R&D, Mene Pangalos, said in a prepared statement that under supply agreements formed at that time the company would derive no profit. That statement was prepared for a congressional hearing.

    Johnson & Johnson, which is also working on a COVID-19 vaccine, has joined AstraZeneca in the no-profit pledge, but other companies haven’t been so enthusiastic about the prospect of not making a return on their investments in helping end the pandemic.

    Pfizer CEO Albert Bourla, for example, said in July that the notion of vaccine developers forgoing profits on COVID-19 vaccines was “very fanatic and radical,” and the company expects to make a “marginal” profit on its vaccine.

    AstraZeneca, which is developing its COVID-19 vaccine with the University of Oxford, has been locking up supply deals to meet what it expects to be a demand for 3 billion doses. Most recently, it formed a $60 million, three-year deal with Oxford Biomedica to reserve vaccine manufacturing space at three sites. Oxford Biomedica nabbed U.K. approval for a fourth vaccine manufacturing site earlier this week.

    The creation of multiple supply chains for the COVID-19 vaccine will “ensure access is timely, broad and equitable for high and low income countries alike,” the spokesperson said.

    AstraZeneca’s COVID-19 vaccine effort has been anything but smooth, however. The clinical trial of the vaccine was paused over safety concerns stemming from the British study, in which one patient suffered spinal cord damage. British regulators quickly resumed the trial there, but it’s still on hold in the U.S. as the National Institutes of Health completes an investigation.

    Scientists look to ease ear-drop dosing with one-time, temp-stable hydrogel for swimmer’s ear

    The market is swimming with ear infection drugs, but keeping up with frequent ear-drop doses can be a metaphorical headache—and a literal earache. But a group of scientists at the University of Montana have developed a temperature-stable, single-dose option, and they have new preclinical data to back it up. Plenty of existing antibiotics can treat acute otitis externa—also known as swimmer’s ear—but patients typically have to take ear drops multiple times a day for several weeks. A single-application gel taken at home could improve adherence, potentially curb bacterial drug resistance and expand access to those living in remote areas, the researchers figure.

    Led by Monica Serban, Ph.D., the team developed two separate hydrogel delivery systems and tested them in a cell and mouse study published in the journal ACS Biomaterials Science & Engineering.

    Both systems combine activated tetraethyl orthosilicate with different large molecules to create a hydrogel, which remains in a liquid state inside a syringe, but quickly forms a gel upon entering the ear, allowing for sustained drug release.

    The team paired those hydrogel systems, stable from about 39 degrees to 104 degrees Fahrenheit, with the antibiotic ciprofloxacin, which itself doesn’t require refrigeration.

    In cell cultures, the drug-infused hydrogels managed to wipe out the bacteria Pseudomonas aeruginosa and Staphylococcus aureus—the two major culprits behind swimmer’s ear—at doses 100 times lower than those used in most ear drops, the team said.

    The gels also proved safe when tested on models of human skin and dissipated within 10 days in mouse ears. They had no significant impact on the mice’s hearing compared to standard ear drops, the team added.

    Serban’s lab recently snared a $1.45 million award from the National Institute of Health for its ear infection efforts, which will allow the team to run further tests on shelf life and stability, ABC Fox Montana reported. If all goes to plan, the product could hit shelves in about two years, the team figures.

    Meanwhile, the FDA in 2018 greenlighted Otonomy’s ciprofloxacin otic suspension, sold as Otiprio, as the first single-dose antibacterial approved to treat swimmer’s ear.

    The drug, first cleared in 2015 to treat young children undergoing tympanostomy tube placement surgery, eliminates outer ear infections after a single dose, but Otiprio must be refrigerated and prepared before use. A medical professional must also administer the drug in the clinic—factors Serban’s team hope to overcome with its room temperature-stable delivery platform.

    Pfizer-BioNTech, Regeneron sued for patent infringement with COVID-19 products

    As Regeneron grabs the limelight for treating President Donald Trump with its experimental COVID-19 antibody cocktail, the company now finds itself alongside vaccine developers Pfizer and BioNTech on the defensive in a lawsuit that claims their coronavirus products infringe upon a patent. Allele Biotechnology and Pharmaceuticals filed two lawsuits against the three drugmakers on Monday. The San Diego firm alleges that Pfizer and BioNTech, with its investigational COVID-19 vaccine BNT162, and Regeneron’s REGN-COV2, were developed using Allele’s mNeonGreen fluorescent protein without the company’s permission.

    To compensate for the alleged infringement, Allele is seeking damages that amount to no less than a reasonable royalty, the company said in its complaint. It’s not immediately clear how much Allele is seeking.

    In a statement, Regeneron said it disagrees with Allele’s claims of infringement and that it will “vigorously defend our position against this lawsuit.” Pfizer didn’t immediately respond to a request for comment.

    Pfizer and BioNTech’s lead candidate, an mRNA shot dubbed BNT162b2 that’s supported by the Trump’s Administration’s Operation Warp Speed, entered a phase 3 efficacy trial in July as the second U.S. program to do so. The pair said on Tuesday that they have started a rolling submission to the European Medicines Agency, which allows for the agency to review an application as clinical data come through.

    As for Regeneron, the company a few days ago unveiled encouraging data from the first 275 patients in a phase 1/2/3 study of REGN-COV2, which combines two types of antibodies against the virus, showing it could help non-hospitalized patients clear the virus and improve in symptoms. The drug made headlines this past week as President Trump received a high dose of the cocktail as part of his COVID-19 treatment.

    But Allele claims that the Regeneron drug was developed with the help of mNeonGreen, pointing to several academic papers published in Science and co-authored by Regeneron employees that include information on how antibodies against SARS-CoV-2’s spike protein were tested with the fluorescent protein.

    In medical research, fluorescent proteins are injected into living cells so that scientists can visualize the molecular changes to determine the cells’ response to treatments. Among them, mNeonGreen is one of the brightest and most stable monomeric fluorescent proteins to date, and therefore allows for rapid detection of changes, according to Allele. “This research tool is even more critical in a global pandemic where the need for a vaccine to save lives has never been more crucial,” the company said in its complaint.

    According to Allele, it “sought on multiple occasions to discuss Regeneron’s taking a license to that patent” but got no reply.

    In Pfizer and BioNTech’s case, Allele said development and testing of the pair’s BNT162 vaccine candidate was made possible “only through use of mNeonGreen,” but the partners never reached out for a license, according to the complaint.

    The tech earned the companies “an immediate $445 million in grants and over $4 billion in sales of the vaccine to date,” the complaint said, likely referring to the government contracts the pair has secured, including a $1.95 billion supply deal with the U.S. government.


    New drug candidate for the treatment of COVID-19

    Researchers from the University of Kent, the Goethe-University in Frankfurt am Main (Germany), and the Hannover Medical School (Germany) have identified a drug with the potential to provide a treatment for COVID-19.
    The international team led by Professor Martin Michaelis, Dr Mark Wass (both School of Biosciences, University of Kent), and Professor Jindrich Cinatl (Institute of Medical Virology, Goethe-University) found that the approved protease inhibitor aprotinin displayed activity against SARS-CoV-2, the coronavirus that causes COVID-19, in concentrations that are achieved in patients. Aprotinin inhibits the entry of SARS-CoV-2 into host cells and may compensate for the loss of host cell protease inhibitors that are downregulated upon SARS-CoV-2 infection.

    Aprotinin aerosols are approved in Russia for the treatment of influenza and could be readily tested for the treatment of COVID-19.

    Professor Martin Michaelis said: “The aprotinin aerosol has been reported to be tolerated extremely well in influenza patients. Hence, it may have a particular potential to prevent severe COVID-19 disease when applied early after diagnosis.”

    Bojkova D, Bechtel M, McLaughlin K-M, McGreig JE, Klann K, Bellinghausen C, Rohde G, Jonigk D, Braubach P, Ciesek S, Münch C, Wass MN, Michaelis M, Cinatl J Jr.
    Aprotinin Inhibits SARS-CoV-2 Replication.
    Cells 2020, 9, 2377. 10.3390/cells9112377

    Oxford COVID-19 vaccine follows its programmed genetic instructions, independent analysis finds

    The AstraZeneca Oxford COVID-19 vaccine (ChAdOx1 nCoV-19 and also known as AZD1222) now undergoing Phase III clinical trials, has already undergone rigorous testing to ensure the highest standards of quality and safety. Now a team at Bristol University has used recently developed techniques to further validate that the vaccine accurately follows the genetic instructions programmed into it by the Oxford team. This novel analysis provides even greater clarity and detail about how the vaccine successfully provokes a strong immune response.
    The findings, led by scientists at the University of Bristol and published on the pre-print server ResearchSquare, represent the most in-depth analysis of any of the COVID-19 vaccine candidates, going significantly above and beyond any regulatory requirements anywhere in the world.

    Work on the vaccine, developed by researchers at the University of Oxford’s Jenner Institute and Oxford Vaccine Group, began in January 2020. Now undergoing Phase III clinical trials by the University of Oxford and AstraZeneca, the Bristol researchers’ focus was to assess how often and how accurately the vaccine is copying and using the genetic instructions provided by the Oxford team. These instructions detail how to make the spike protein from the coronavirus, SARS-CoV-2 that causes COVID-19.

    The Oxford vaccine is made by taking a common cold virus (adenovirus) from chimpanzees and deleting about 20 per cent of the virus’s instructions. This means it is impossible for the vaccine to replicate or cause disease in humans, but it can still be produced in the laboratory under special conditions. By removing these genetic instructions there is space to add the instructions for the spike protein from SARS-CoV-2. Once inside a human cell the genetic instructions for the spike protein need to be ’photocopied’ many times – a process known as transcription. In any vaccine system, it is these ’photocopies’ that are directly used to make large amounts of the spike protein.

    Once the spike protein is made, the immune system will react to it and this pre-trains the immune system to identify a real COVID-19 infection. So, when the person vaccinated is confronted with the SARS-CoV-2 virus their immune system is pre-trained and ready to attack it.

    Adenoviruses have been used for many years to make vaccines, and these are always tested to very high standards to make sure every batch of vaccine has the correct copy of genetic instructions embedded in the vaccine. However, thanks to very recent advances in genetic sequencing and protein analysis technology, researchers at Bristol were for the first time also able to directly check thousands and thousands of the ‘photocopied’ instructions produced by the Oxford vaccine within a cell. In this way they were able to directly validate that the instructions are copied correctly and accurately, providing greater assurance that the vaccine is performing exactly as programmed. At the same time, the researchers checked the spike protein being made by the vaccine inside human cells also accurately reflects the instructions as programmed. This brand-new approach may be more routinely used in the future to help researchers fine tune the performance of these kinds of vaccines.

    Dr David Matthews, Reader in Virology from Bristol’s School of Cellular and Molecular Medicine (CMM), who led the research, said: “This is an important study as we are able to confirm that the genetic instructions underpinning this vaccine, which is being developed as fast as safely possible, are correctly followed when they get into a human cell.

    “Until now, the technology hasn’t been able to provide answers with such clarity, but we now know the vaccine is doing everything we expected and that is only good news in our fight against the illness.”

    The study at Bristol was facilitated with support from Dr Andrew Davidson, Reader in Systems Virology in CMM and Bristol UNCOVER and through key collaborations with Sarah Gilbert, Professor of Vaccinology at the University of Oxford, and AstraZeneca.

    Sarah Gilbert, Professor of Vaccinology at the University of Oxford and lead on the Oxford vaccine trial, added: “This is a wonderful example of cross-disciplinary collaboration, using new technology to examine exactly what the vaccine does when it gets inside a human cell. The study confirms that large amounts of the coronavirus spike protein are produced with great accuracy, and this goes a long way to explaining the success of the vaccine in inducing a strong immune response.”

    The study was funded by the Biotechnology and Biological Sciences Research Council (BBSRC), the United States Food and Drug Administration (US FDA) and the Engineering and Physical Sciences Research Council (EPSRC).

    ‘SARS-CoV-2 candidate vaccine ChAdOx1 nCoV-19 infection of human cell lines reveals a normal low range of viral backbone gene expression alongside very high levels of SARS-CoV-2 S glycoprotein expression’ by Abdulaziz Almuqrin, Andrew D. Davidson, Maia Kavanagh Williamson, Phil Lewis, Kate Heesom, Susan Morris, Sarah Gilbert, David A. Matthews in ResearchSquare

    Please note this is a preprint, so it is a preliminary piece of research that has not yet been through peer review and has not been published in a scientific journal – so this is early data.

    Popular COVID-19 conspiracies linked to vaccine ‘hesitancy’

    A new study of beliefs and attitudes toward COVID-19 in five different countries – UK, US, Ireland, Mexico and Spain – has identified how much traction some prominent conspiracy theories have within these populations.
    The research reveals ‘key predictors’ for susceptibility to fake pandemic news, and finds that a small increase in the perceived reliability of conspiracies equates to a larger drop in the intention to get vaccinated.

    Scientists from the University of Cambridge gathered data from national samples in each country, and asked participants to rate the reliability of several statements, including six popular myths about COVID-19.

    While a large majority of people in all five nations judged the misinformation to be unreliable, researchers found that certain conspiracy theories have taken root in significant portions of the population.

    The conspiracy deemed most valid across the board was the claim that COVID-19 was engineered in a Wuhan laboratory. Between 22-23% of respondents in the UK and United States rated this assertion as “reliable”. In Ireland this rose to 26%, while in Mexico and Spain it jumped to 33% and 37% respectively.

    This was followed by the idea that the pandemic is “part of a plot to enforce global vaccination”, with 22% of the Mexican population rating this as reliable, along with 18% in Ireland, Spain and the US, and 13% in the UK.

    The notorious 5G conspiracy – that some telecommunication towers are worsening COVID-19 symptoms – holds sway over smaller but still significant segments: 16% in Mexico, 16% in Spain, 12% in Ireland, and 8% in both the UK and US. The study is published today in the journal Royal Society Open Science.

    “Certain misinformation claims are consistently seen as reliable by substantial sections of the public. We find a clear link between believing coronavirus conspiracies and hesitancy around any future vaccine,” said Dr Sander van der Linden, co-author and Director of the Cambridge Social Decision-Making Lab.

    “As well as flagging false claims, governments and technology companies should explore ways to increase digital media literacy in the population. Otherwise, developing a working vaccine might not be enough.”

    Earlier this week, the Social Decision-Making Lab launched a project with the UK Cabinet Office: Go Viral!, a short online game that helps ‘inoculate’ players against fake news by lifting the lid on common misinformation techniques.

    For the new study, the team – including Cambridge’s Winton Centre for Risk and Evidence Communication – looked at correlations between certain beliefs and demographic categories and the perceived reliability of misinformation.

    Scoring highly on a series of numeracy tasks given as part of the study, as well as declaring high levels of trust in scientists, are ‘significantly and consistently’ associated with low levels of susceptibility to false information across all nations.

    “Numeracy skills are the most significant predictor of resistance to misinformation that we found,” said Dr Jon Roozenbeek, lead author and Postdoctoral Fellow in Cambridge’s Department of Psychology.

    “We all now deal with a deluge of statistics and R number interpretations. The fostering of numerical skills for sifting through online information could well be vital for curbing the ‘infodemic’ and promoting good public health behaviour.”

    Moreover, and despite ‘boomer’ memes, the team found that being older is actually linked to lower susceptibility to COVID-19 misinformation in all nations except Mexico (where the opposite is true).

    Identifying as more right-wing or politically conservative is associated with higher likelihood of believing COVID-19 conspiracies and falsehoods in Ireland, Mexico and Spain – but less so in the UK or US.

    Trusting that politicians can effectively tackle the crisis predicts higher likelihood of buying into conspiracies in Mexico, Spain and the US, but not in the UK and Ireland. Exposure to information about the virus on social media is linked to misinformation susceptibility in Ireland, the UK and US.

    Researchers asked participants about their attitude to a future coronavirus vaccine. They were also asked to rate the reliability of conspiratorial COVID-19 claims on a scale of one to seven.

    On average, an increase by one-seventh in someone’s perceived reliability of misinformation is associated with a drop of almost a quarter – 23% – in the likelihood they will agree to get vaccinated.

    Similarly, a one-point increase on the conspiracy reliability scale is linked, on average, to a 28% decrease in the odds of someone recommending vaccination to vulnerable friends and family.

    Conversely, on average, a one-seventh increase in trust in scientists is associated with a 73% increase in the likelihood of getting vaccinated and a 79% increase in the odds of recommending vaccination to others.

    The researchers controlled for many other factors – from age to politics – when modelling levels of ‘vaccine hesitancy’, and found the results to be consistent across all countries except Spain.

    Jon Roozenbeek, Claudia R Schneider, Sarah Dryhurst, John Kerr, Alexandra LJ Freeman, Gabriel Recchia, Anne Marthe van der Bles, Sander van der Linden.
    Susceptibility to misinformation about COVID-19 around the world.
    R. Soc. Open Sci., 2020, doi: 10.1098/rsos.201199

    Can an antibody ‘cocktail’ prevent COVID-19 infection?

    Stuart Cohen, chief of the Division of Infectious Diseases and director of Hospital Epidemiology and Infection Prevention at UC Davis Health, will oversee the clinical trial and help recruit participants. “We at UC Davis Health are very excited to be part of this clinical trial and to study antibodies which have been used in the past to prevent many viral infections, such as hepatitis B, after exposure,” Cohen said. “We will test the ability of REGN-COV2 to prevent COVID-19 infection in people who have had close exposure to a diagnosed patient, such as a household member.”

    The trial, sponsored by Regeneron Pharmaceuticals, is in Phase III to evaluate the efficacy, tolerability and safety of REGN-COV2 in adults with no history of SAR-Cov-2 infection but who live with someone who has COVID-19. Study participants will be randomly assigned to either an experimental group receiving the active medication or to the control group taking the placebo. As a double-blinded study, both the participants and the researchers will not know the group assignments.

    The participants must have been in close contact with the infected person for no more than 96 hours before receiving either REGN-CoV-2 or the placebo. The trial seeks to determine whether it can prevent infection for one month following the drug administration.

    On Oct. 6, the UC Davis Health team enrolled its first patient.

    The antibody cocktail as a potential preventive measure for COVID-19

    Regeneron developed the REGN-COV2 antibodies (a combination of REGN10933 + REGN10987 antibodies) to bind to the SARS-CoV-2 spike protein and block its interaction with the host receptor. The trial builds on encouraging findings from a set of studies that showed the neutralizing impact of REGN10933 and REGN10987. In addition to this clinical trial, UC Davis Health is involved in testing this antibody combination as a treatment for patients with COVID-19.

    According to Regeneron, antibody approaches could serve as an important ‘bridge’ until a vaccine is widely available.

    The clinical study (#NCT04452318) is titled “A Phase 3, Randomized, Double-Blind, Placebo-Controlled Study Assessing Efficacy and Safety of Anti-Spike SARS-CoV-2 Monoclonal Antibodies in Preventing SARS-Cov-2 Infection in Household Contacts of Individuals Infected w/ SARS-CoV-2.”

    Strong activation of anti-bacterial T cells linked to severe COVID-19

    A type of anti-bacterial T cells, so-called MAIT cells, are strongly activated in people with moderate to severe COVID-19 disease, according to a study by researchers at Karolinska Institutet in Sweden that is published in the journal Science Immunology. The findings contribute to increased understanding about how our immune system responds against COVID-19 infection. “To find potential treatments against COVID-19, it is important to understand in detail how our immune system reacts and, in some cases, perhaps contribute to worsening the disease,” says Johan Sandberg, professor at the Department of Medicine, Huddinge, at Karolinska Institutet and the study’s corresponding author.

    T cells are a type of white blood cells that are specialized in recognizing infected cells, and are an essential part of the immune system. About 1 to 5 percent of T cells in the blood of healthy people consist of so-called MAIT cells (mucosa-associated invariant T cells), which are primarily important for controlling bacteria but can also be recruited by the immune system to fight some viral infections.

    In this study, the researchers wanted to find out which role MAIT cells play in COVID-19 disease pathogenesis. They examined the presence and character of MAIT cells in blood samples from 24 patients admitted to Karolinska University Hospital with moderate to severe COVID-19 disease and compared these with blood samples from 14 healthy controls and 45 individuals who had recovered from COVID-19. Four of the patients died in the hospital.

    The results show that the number of MAIT cells in the blood decline sharply in patients with moderate or severe COVID-19 and that the remaining cells in circulation are highly activated, which suggests they are engaged in the immune response against SARS-CoV-2. This pattern of reduced number and activation in the blood is stronger for MAIT cells than for other T cells. The researchers also noted that pro-inflammatory MAIT cells accumulated in the airways of COVID-19 patients to a larger degree than in healthy people.

    “Taken together, these analyses indicate that the reduced number of MAIT cells in the blood of COVID-19 patients is at least partly due increased accumulation in the airways,” Johan Sandberg says.

    In convalescent patients, the number of MAIT cells in the blood recovered at least partially in the weeks after disease, which can be important for managing bacterial infections in individuals who have had COVID-19, according to the researchers. In the patients who died, the researchers noted that the MAIT cells tended to be extremely activated with lower expression of the receptor CXCR3 than in those who survived.

    “The findings of our study show that the MAIT cells are highly engaged in the immunological response against COVID-19,” Johan Sandberg says. “A likely interpretation is that the characteristics of MAIT cells make them engaged early on in both the systemic immune response and in the local immune response in the airways to which they are recruited from the blood by inflammatory signals. There, they are likely to contribute to the fast, innate immune response against the virus. In some people with COVID-19, the activation of MAIT cells becomes excessive and this correlates with severe disease.”

    Parrot T, Gorin JB, Ponzetta A, Maleki KT, Kammann T, Emgård J, Perez-Potti A, Sekine T, Rivera-Ballesteros O, the Karolinska COVID-19 Study Group, Gredmark-Russ S, Rooyackers O, Folkesson, E, Eriksson LI, Norrby-Teglund A, Ljunggren HG, Björkström NK, Aleman S, Buggert M, Klingström J, Strålin K, Sandberg JK.
    MAIT cell activation and dynamics associated with COVID-19 disease severity.
    Science Immunology, 2020. doi: 10.1126/sciimmunol.abe1670

    Boost for global response to COVID-19 as economies worldwide formally sign up to COVAX facility

    64 higher income economies have joined the COVAX Facility, a global initiative that brings together governments and manufacturers to ensure eventual COVID-19 vaccines reach those in greatest need, whoever they are and wherever they live. These 64 economies include commitments from 35 economies as well as the European Commission which will procure doses on behalf of 27 EU member states plus Norway and Iceland. By pooling financial and scientific resources, these participating economies will be able to insure themselves against the failure of any individual vaccine candidate and secure successful vaccines in a cost-effective, targeted way.

    The 64 members of the Facility will be joined by 92 low- and middle-income economies eligible for support for the procurement of vaccines through the Gavi COVAX Advance Market Commitment (AMC), a financing instrument aimed at supporting the procurement of vaccines for these countries. This means that 156 economies, representing roughly 64% of the global population in total, are now either committed to or eligible for the COVAX Facility, with more to follow.

    With the Commitment Agreements secured, the COVAX Facility will now start signing formal agreements with vaccine manufacturers and developers, which are partners in the COVAX effort, to secure the doses needed to end the acute phase of the pandemic by the end of 2021. This is in addition to an ongoing effort to raise funding for both R&D and for the procurement of vaccines for lower-income countries via the Gavi COVAX AMC.

    “COVAX is now in business: governments from every continent have chosen to work together, not only to secure vaccines for their own populations, but also to help ensure that vaccines are available to the most vulnerable everywhere,” said Dr Seth Berkley, CEO of Gavi, the Vaccine Alliance, which is coordinating the COVAX Facility. “With the commitments we’re announcing today for the COVAX Facility, as well as the historic partnership we are forging with industry, we now stand a far better chance of ending the acute phase of this pandemic once safe, effective vaccines become available.”

    The COVAX Facility is part of COVAX, the vaccines pillar of the Access to COVID-19 Tools (ACT) Accelerator, which is co-led by the Coalition for Epidemic Preparedness Innovations (CEPI), Gavi, the Vaccine Alliance, and the World Health Organization (WHO) – working in partnership with developed and developing country vaccine manufacturers, UNICEF, the World Bank, Civil Society Organisations and others.

    The allocation of vaccines, once licensed and approved, will be guided by an Allocation Framework released today by WHO following the principle of fair and equitable access, ensuring no participating economy will be left behind. Policies determining the prioritization of vaccine rollout within economies will be guided by recommendations from the WHO Strategic Advisory Group of Experts on Immunization (SAGE), which has recently released a Values Framework laying the groundwork for subsequent guidance on target populations and policies on vaccine use.

    “COVID-19 is an unprecedented global crisis that demands an unprecedented global response,” said WHO Director-General, Dr Tedros Adhanom Ghebreyesus. “Vaccine nationalism will only perpetuate the disease and prolong the global recovery. Working together through the COVAX Facility is not charity, it’s in every country’s own best interests to control the pandemic and accelerate the global economic recovery.”

    The commitment of fully self-financing economies will now unlock vital funding and the security of demand needed to scale up manufacturing and secure the doses needed for the Facility. CEPI is leading COVAX vaccine research and development work, which aims to develop at least three safe and effective vaccines which can be made available to economies participating in the COVAX Facility. Nine candidate vaccines are currently being supported by CEPI; eight of which are currently in clinical trials.

    “This is a landmark moment in the history of public health with the international community coming together to tackle this pandemic. The global spread of COVID-19 means that it is only through equitable and simultaneous access to new lifesaving COVID-19 vaccines that we can hope to end this pandemic,” said Dr Richard Hatchett, CEO of CEPI. “Countries coming together in this way shows a unity of purpose and resolve to end the acute phase of this pandemic, and we must now work closely with vaccine manufacturers – who play an integral part in the global response – to put in place the agreements needed to fulfil COVAX’s core aim: to have two billion vaccine doses available by the end of 2021. Today, we have taken a great leap towards that goal, for the benefit of all.”

    The success of COVAX hinges not only on economies signing up to the COVAX Facility and commitments from vaccine manufacturers, but also filling key funding gaps for both COVAX research and development (R&D) work and the Gavi COVAX AMC to support participation of lower income economies in the COVAX Facility.

    Governments, vaccine manufacturers (in addition to their own R&D), organisations and individuals have committed US$ 1.4 billion towards vaccine R&D so far, but a further US$ 700-800 million is urgently needed to continue to move the portfolio forward in addition to US$ 300 million to fund WHO’s SOLIDARITY trial.

    The Gavi COVAX AMC has raised around US$ 700 million from sovereign donors as well as philanthropy and the private sector, against an initial target of US$ 2 billion in seed funding needed by the end of 2020. Funding the Gavi COVAX AMC will be critical to ensuring ability to pay is not a barrier to accessing COVID-19 vaccines, a situation which would leave the majority of the world unprotected, with the pandemic and its impact continuing unabated.

    The Commitment Agreements also commit higher income governments to provide an upfront payment to reserve doses by 9 October 2020. These funds will be used to accelerate the scale-up of vaccine manufacturing to secure two billion doses of vaccine, enough to vaccinate one billion people assuming the vaccine requires a two-dose regimen. Further details on these upfront payments are available in Gavi’s COVAX Facility Explainer.

    As well as procuring doses for participating economies, the COVAX Facility will also maintain a buffer of doses for emergency and humanitarian use.

    About Gavi, the Vaccine Alliance

    Gavi, the Vaccine Alliance is a public-private partnership that helps vaccinate half the world’s children against some of the world’s deadliest diseases. Since its inception in 2000, Gavi has helped to immunise a whole generation – over 760 million children – and prevented more than 13 million deaths, helping to halve child mortality in 73 developing countries. Gavi also plays a key role in improving global health security by supporting health systems as well as funding global stockpiles for Ebola, cholera, meningitis and yellow fever vaccines. After two decades of progress, Gavi is now focused on protecting the next generation and reaching the unvaccinated children still being left behind, employing innovative finance and the latest technology – from drones to biometrics – to save millions more lives, prevent outbreaks before they can spread and help countries on the road to self-sufficiency.

    The Vaccine Alliance brings together developing country and donor governments, the World Health Organization, UNICEF, the World Bank, the vaccine industry, technical agencies, civil society, the Bill & Melinda Gates Foundation and other private sector partners.

    About CEPI

    CEPI is an innovative partnership between public, private, philanthropic, and civil organisations, launched at Davos in 2017, to develop vaccines to stop future epidemics. CEPI has moved with great urgency and in coordination with WHO in response to the emergence of COVID-19. CEPI has initiated nine partnerships to develop vaccines against the novel coronavirus. The programmes are leveraging rapid response platforms already supported by CEPI as well as new partnerships.

    Before the emergence of COVID-19, CEPI’s priority diseases included Ebola virus, Lassa virus, Middle East Respiratory Syndrome coronavirus, Nipah virus, Rift Valley Fever and Chikungunya virus. CEPI also invested in platform technologies that can be used for rapid vaccine and immunoprophylactic development against unknown pathogens (Disease X).

    About WHO

    The World Health Organization provides global leadership in public health within the United Nations system. Founded in 1948, WHO works with 194 Member States, across six regions and from more than 150 offices, to promote health, keep the world safe and serve the vulnerable. Our goal for 2019-2023 is to ensure that a billion more people have universal health coverage, to protect a billion more people from health emergencies, and provide a further billion people with better health and wellbeing.

    About ACT-Accelerator

    The Access to COVID-19 Tools ACT-Accelerator, is a new, ground-breaking global collaboration to accelerate the development, production, and equitable access to COVID-19 tests, treatments, and vaccines. It was set up in response to a call from G20 leaders in March and launched by the WHO, European Commission, France and The Bill & Melinda Gates Foundation in April 2020.

    The ACT-Accelerator is not a decision-making body or a new organisation, but works to speed up collaborative efforts among existing organisations to end the pandemic. It is a framework for collaboration that has been designed to bring key players around the table with the goal of ending the pandemic as quickly as possible through the accelerated development, equitable allocation, and scaled up delivery of tests, treatments and vaccines, thereby protecting health systems and restoring societies and economies in the near term. It draws on the experience of leading global health organisations which are tackling the world’s toughest health challenges, and who, by working together, are able to unlock new and more ambitious results against COVID-19. Its members share a commitment to ensure all people have access to all the tools needed to defeat COVID-19 and to work with unprecedented levels of partnership to achieve it.

    The ACT-Accelerator has four areas of work: diagnostics, therapeutics, vaccines and the health system connector. Cross-cutting all of these is the workstream on Access & Allocation.

    Protective antibodies persist for months in survivors of serious COVID-19 infections

    People who survive serious COVID-19 infections have long-lasting immune responses against the virus, according to a new study led by researchers at Massachusetts General Hospital (MGH). The study, published in Science Immunology, offers hope that people infected with the virus will develop lasting protection against reinfection. The study also demonstrates that measuring antibodies can be an accurate tool for tracking the spread of the virus in the community.

    The immune system produces proteins called antibodies in response to SARS-CoV-2, the virus that causes COVID-19. “But there is a big knowledge gap in terms of how long these antibody responses last,” says Richelle Charles, MD, an investigator in the Division of Infectious Diseases at MGH and a senior author of the paper. To find out, she and her colleagues obtained blood samples from 343 patients with COVID-19, most of whom had severe cases. The blood samples were taken up to four months after a patient’s symptoms emerged. The blood’s plasma was isolated and applied to laboratory plates coated with the receptor-binding domain (RBD) of the virus’s “spike” protein, which attaches to cells, leading to infection. The team studied how different types of antibodies in the plasma bound to RBD. The results were compared to blood samples obtained from more than 1,500 individuals prior to the pandemic.

    The researchers found that measuring an antibody called immunoglobulin G (IgG) was highly accurate in identifying infected patients who had symptoms for at least 14 days. Since the standard PCR (nasal swab) test for SARS-CoV-2 loses sensitivity over time, augmenting it with a test for antibodies in patients who have had symptoms for at least eight days (at which time 50 percent are producing antibodies) will help identify some positive cases that might otherwise be missed, says Charles.

    The researchers found that IgG levels remained elevated in these patients for four months, and were associated with the presence of protective neutralizing antibodies, which also demonstrated little decrease in activity over time. “That means that people are very likely protected for that period of time,” says Charles. “We showed that key antibody responses to COVID-19 do persist.”

    In another finding, Charles and her colleagues showed that people infected with SARS-CoV-2 had immunoglobulin A (IgA) and immunoglobulin M (IgM) responses that were relatively short-lived, declining to low levels within about two and a half months or less, on average. “We can say now that if a patient has IgA and IgM responses, they were likely infected with the virus within the last two months,” says Charles.

    Knowing the duration of the immune response by IgA and IgM will help scientists obtain more accurate data about the spread of SARS-CoV-2, explains Jason Harris, MD, a pediatric infectious disease specialist at MGH and co-senior author of the study. “There are a lot of infections in the community that we do not pick up through PCR testing during acute infection, and this is especially true in areas where access to testing is limited,” he says. “Knowing how long antibody responses last is essential before we can use antibody testing to track the spread of COVID-19 and identify ‘hot spots’ of the disease.”

    Anita S Iyer, Forrest K Jones, Ariana Nodoushani, Meagan Kelly, Margaret Becker, Damien Slater, Rachel Mills, Erica Teng, Investigation, Mohammad Kamruzzaman, Wilfredo F Garcia-Beltran, Michael Astudillo, Diane Yang, Tyler E. Miller, Elizabeth Oliver, Stephanie Fischinger, Caroline Atyeo, A John Iafrate, Stephen B Calderwood, Stephen A Lauer, Methodology, Supervision, Validation, Jingyou Yu, Zhenfeng Li, Jared Feldman, Blake M Hauser, Timothy M Caradonna, John A Branda, Sarah E Turbett, Regina C LaRocque, Guillaume Mellon, Dan H Barouch, Aaron G Schmidt, Andrew S Azman, Galit Alter, Edward T Ryan, Jason B Harris, Richelle C Charles.
    Persistence and decay of human antibody responses to the receptor binding domain of SARS-CoV-2 spike protein in COVID-19 patients.
    Science Immunology, 2020. doi: 10.1126/sciimmunol.abe0367

    New clinical trial for a COVID-19 vaccine authorised in Germany

    The Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines has authorised another Phase-1 clinical trial of a vaccine against COVID-19 in Germany. The new vaccine candidate is a so-called vector vaccine. Trials on vaccine candidates in humans are a significant step in the direction of authorising safe and efficacious vaccines against COVID-19. This new vaccine is a vector vaccine developed by the German Center for Infection Research (Deutsches Zentrum für Infektionsforschung, DZIF) and the IDT Biologika GmbH against SARS-CoV-2. In this vector vaccine, the genetic information for the spike surface protein of the SARS-CoV-2 virus is built into the smallpox vaccine virus MVA. The starting vaccine virus MVA was already developed more than 30 years ago at the Ludwig-Maximilians University (LMU) in Munich, and the authorised smallpox vaccine Imvanex was derived from it. The viral vector MVA equipped with the genetic information of SARS-CoV-2 cannot replicate in the body after injection. The genetic information (desoxyribonucleic acid, DNA) of the spike protein of the virus thus inserted is used in the body to form the spike protein. The immune system recognises the foreign spike protein and triggers an immune response. The aim is to generate antibodies, certain cytokines and immune cells (T cells) for lasting protection against SARS-CoV-2. Preclinical models at the universities of Marburg and Munich have already shown that the MVA vector vaccine against SARS-CoV-2 shows the desired immune responses and a protective effect.

    The clinical trial authorised by the Paul-Ehrlich-Institut on 30 September 2020 is a phase 1 clinical trial with altogether 30 healthy subjects aged between 18 and 55 years. The participants receive two vaccinations at an interval of four weeks. The working group at the University Medical Center Hamburg-Eppendorf (UKE) and the DZIF partner in Marburg are simultaneously measuring the formation of antibodies and T cells in the body and comparing them with the immune response of recovered COVID-19 patients. The UKE is responsible for the clinical trial, which is carried out jointly with the contracted medical institute CTC North. The study is financed by public funds from the DZIF.

    According to the World Health Organisation (WHO), as per 30 September 2020, the vaccine candidate is one of the 41 preventive specific COVID-19 vaccine candidates being evaluated in clinical trials. In Germany, it represents the first authorised phase 1 clinical trial for a vector-based COVID-19 vaccine. The increasing number of clinical trials worldwide is an important step toward authorising safe and efficacious COVID-19 vaccine products.

    The Paul-Ehrlich-Institut, which is the competent authority for authorising clinical trials and the evaluation and marketing authorisation of vaccines in Germany, expects additional clinical trials for COVID-19 vaccine candidates to start in Germany in the next few months. The Paul-Ehrlich-Institut supports the worldwide COVID-19 vaccine development with top priority.

    Background for Vector Vaccines

    COVID-19 vector vaccines contain innocuous parts of the genome of SARS-CoV-2 in their genetic information, i.e. the blueprint for the spike protein or for a component of that spike protein. After this genetic information has entered a few body cells of the vaccinated subject, it is read (like the genetic information of the body cells itself) in the cells as messenger RNA, and the appropriate surface structures (proteins) of the virus are produced. The immune system reacts to the foreign protein thus formed and forms defences against it (among other things antibodies). If the person thus vaccinated comes into contact with SARS-CoV-2 later on, the immune system will recognise the surface structure with the aim to prevent or alleviate a serious course of a COVID-19 infection, and even to reduce the transmission of SARS-CoV-2 from human to human.

    Researchers call for loss of smell to be recognized globally as a symptom of COVID-19

    Four out of five people experiencing the recent loss of smell and/or taste tested positive for COVID-19 antibodies – and of those who tested positive, 40 percent did not have cough or fever, reports a new study in PLOS Medicine by Prof. Rachel Batterham at University College London and colleagues. COVID-19 can cause loss of taste and smell, but the prevalence of COVID-19 antibodies in people reporting these symptoms is unknown, and the significance of loss of smell and/or taste as a predictor of COVID-19 is not well understood. To estimate the seroprevalence of SARS-CoV-2 antibodies in people with acute loss of their sense of smell and/or taste, researchers enrolled 590 people self-reporting a loss of taste/smell in the previous month. Following verification of symptoms via a telemedicine consultation, 567 participants with smell and/or taste loss participants underwent a SARS-CoV-2 antibodies test.

    78% had SARS-CoV-2 antibodies, and participants with loss of smell were almost 3 times more likely to have SARS-CoV-2 antibodies compared to those with loss of taste, suggesting that a loss of smell is a highly specific symptom of COVID-19. Of the 78% of participants testing positive for antibodies, 40% had neither cough nor fever. While the study had limitations, such as the self-reporting of smell/taste changes and the lack of a control group, the researchers believe the evidence indicates that loss of smell should be taken into greater consideration in COVID-19 public health measures such as testing, case isolation, and treatment strategies.

    These findings also have significant implications for policy makers globally, as most countries do not recommend self-isolation and testing based on acute loss of smell/taste. This study suggests that an over-reliance on cough and fever as the main symptoms of COVID-19 may be flawed and that loss of smell needs to be urgently recognized globally as a key symptom of COVID-19.

    Prof. Rachel Batterham, who led the study, said “Early self-recognition of COVID-19 symptoms by the members of the public, together with rapid self-isolation and PCR testing are vital in order to limit spread of the disease. Currently, most countries around the world do not recognize sudden loss of smell as a symptom of COVID-19.

    78% of participants in our community-based study with sudden onset loss of smell or taste had SARS-CoV-2 antibodies. The vast majority had mild symptoms and 40% did not report having a fever or cough. Our findings suggest that people who notice a loss in their ability to smell every day house-hold odors such as garlic, coffee and perfumes should self-isolate and seek PCR testing. Loss of sense of smell needs to be recognized globally by policy makers as a key symptom of COVID-19.”

    Makaronidis J, Mok J, Balogun N, Magee CG, Omar RZ, et al.
    Seroprevalence of SARS-CoV-2 antibodies in people with an acute loss in their sense of smell and/or taste in a community-based population in London, UK: An observational cohort study.
    PLOS Medicine 2020, doi: 10.1371/journal.pmed.1003358