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EU adds another rare blood condition as side effect of AstraZeneca shot

Europe’s drug regulator on June 11 identified another rare blood condition as a potential side effect of AstraZeneca’s Covid-19 vaccine and said it was looking into cases of heart inflammation after inoculation with all coronavirus shots.

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EU adds another rare blood condition as side effect of AstraZeneca shot

(Reuters; )

Europe’s drug regulator on Friday identified another rare blood condition as a potential side effect of AstraZeneca’s (AZN.L) COVID-19 vaccine and said it was looking into cases of heart inflammation after inoculation with all coronavirus shots.

The European Medicines Agency’s (EMA) safety committee said that capillary leak syndrome must be added as a new side effect to labelling on AstraZeneca’s vaccine, known as Vaxzevria.

People who had previously sustained the condition, where fluids leak from the smallest blood vessels causing swelling and a drop in blood pressure, should not receive the shot, the EMA added.

The regulator first began looking into these cases in April and the recommendation adds to AstraZeneca’s woes after its vaccine was associated with very rare and potentially lethal cases of blood clotting that come with a low platelet count.

Last month, the EMA had advised against using the second AstraZeneca shot for people with that clotting condition, known as thrombosis with thrombocytopenia syndrome (TTS).

The committee reviewed six validated cases of capillary leak syndrome in people, mostly women, who had received Vaxzevria, including one death. Three had had a history of the condition.

A vial of AstraZeneca coronavirus vaccine is seen at a vaccination centre in Westfield Stratford City shopping centre, amid the outbreak of coronavirus disease (COVID-19), in London, Britain, February 18, 2021. REUTERS/Henry Nicholls/File Photo

AstraZeneca declined to immediately comment.

More than 78 million Vaxzevria doses have been administered in the European Union, Liechtenstein, Iceland & Norway and Britain.

Britain’s regulator, the MHRA said on Thursday it had received 8 reports of capillary leak syndrome in the context of more than 40 million doses of the AstraZeneca vaccine given, and currently does not see a causal link.

Separately, the EMA said it was continuing its probe into cases of heart inflammation known as myocarditis and pericarditis, primarily following inoculation with the Pfizer/BioNTech (PFE.N), (22UAy.DE) and Moderna mRNA shots, but also after the J&J (JNJ.N) and AstraZeneca vaccines.

U.S. health officials said on Thursday they had registered a higher-than-expected number of heart inflammation cases in young men who received a second dose of the mRNA shots, though a causal relationship could not be established. read more

Israel’s Health Ministry said this month it had found a likely link to the condition in young men who received the Pfizer/BioNTech shot. read more

Both Pfizer and Moderna have acknowldged the observations but said a causal association with their vaccines has not been established.

BioNTech said adverse events, including myocarditis and pericarditis, are being regularly and thoroughly reviewed by the companies and regulatory authorities.

“More than 300 million doses of the Pfizer-BioNTech COVID-19 vaccine have been administered globally and the benefit risk profile of our vaccine remains positive.”

The United States and Israel have been months ahead of the EU in vaccinating men below 30, who are particularly prone to heart inflammation, giving them potentially more cases to analyse.

Our Standards: The Thomson Reuters Trust Principles.

 

Reuters source:

https://www.reuters.com/business/healthcare-pharmaceuticals/eu-advises-against-astrazeneca-shot-people-with-rare-blood-condition-2021-06-11

 

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Computers calling time on isolation

Kyoto–Across the world, many people infected with Covid-19 have been made to completely isolate from others in order to avoid passing on the infection….

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Kyoto–Across the world, many people infected with Covid-19 have been made to completely isolate from others in order to avoid passing on the infection. Some countries still recommend minimum isolation periods for as long as 10 days from when patients start to develop Covid-19 symptoms.

Credit: LAIMAN

Kyoto–Across the world, many people infected with Covid-19 have been made to completely isolate from others in order to avoid passing on the infection. Some countries still recommend minimum isolation periods for as long as 10 days from when patients start to develop Covid-19 symptoms.

Professor Shingo Iwami, affiliated with Kyoto University’s Mathematical Biology Laboratory at the Institute Advanced Study of Human Biology (WPI-ASHBi) says, “Although a long time for isolation reduces the overall risk of patients passing on the infection, there will always be patients who recover early and have to accept several days of redundant isolation while no longer posing an infection risk. We would like to calculate a way to reduce this unnecessary disruption in people’s lives as well as the broader losses for the economy.”

Writing in the journal Nature Communications, an international team of scientists, led by Iwami, has reported a simulation of the potential risks and benefits of ending an individual’s isolation early using antigen tests instead of isolating patients for a fixed time. They call for more sensitive and regular antigen testing to help reduce isolation periods for patients recovering from Covid-19.

The team decided to base their model on antigen rather than PCR testing, trading sensitivity for short turn-around time, low cost, and practicality. Iwami explains that although antigen tests do have a risk of generating “false-negatives” and fail to detect individuals who could still be infectious, there are clear benefits to getting results within an hour rather than waiting a day.

Their model accounts for the sensitivity of antigen tests as well as factors like the amount of virus in a patient that makes them infectious. These are then balanced against the acceptable risk of missing unrecovered and potentially infectious patients, by letting them out of isolation early.

Using their model, the team compared different scenarios to identify the best strategy. For example, the model projects that letting a recovering patient leave isolation after 2 consecutive negative results on 2 days in a row would spend 3.9 days of redundant isolation after their recovery. But under these conditions 1 in 40 patients would continue to pose an infection risk.

More conservative approaches might increase the burden on patients by requiring more than 2 consecutive negative test results of antigen tests.

Iwami says, “The epidemic has still not completely subsided, and we are living with a lot of uncertainty with regard to new variants of the virus. Antigen tests could help, but there is also a real need for worldwide systematic guidelines that simultaneously reduce risks and burdens. We hope this simulator will help doctors and policy makers meet those demands.”

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About WPI-ASHBi https://ashbi.kyoto-u.ac.jp/
Institute for the Advanced Study of Human Biology (ASHBi) was launched in October 2018 with funding from the World Premier International Research Center Initiative (WPI) Program of the Ministry of Education, Culture, Sports, Science and Technology (MEXT). The Institute inaugurated with 18 principal investigators (PIs) to create and promote human biology to elucidate key principles of human traits, including disease states. The Institute will perform interdisciplinary research between biology and mathematics (machine learning and topological data analysis) and between biology and humanities/social sciences (bioethics and philosophy on life), respectively. The Institute implements three research development cores for cutting-edge single-cell genome information analysis, primate genome editing, and non-human primate phenotype analysis, respectively. The Institute establishes a link with international institutions such as the EMBL, University of Cambridge, and Karolinska Institutet, creating a stratified organization for research promotion and strengthening its international profile.


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Someone old, someone new: Moderna promotes CTO, raids Novartis for replacement amid pipeline push

Moderna CEO Stéphane Bancel made clear on the last quarterly call that “now is not the time to slow down.” On Thursday, he made a bit more room in…

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Moderna CEO Stéphane Bancel made clear on the last quarterly call that “now is not the time to slow down.” On Thursday, he made a bit more room in the cockpit.

Juan Andres

The company unveiled a new executive role on Thursday, promoting former chief technical operations and quality officer Juan Andres to president of strategic partnerships and enterprise expansion, and poaching a former Novartis exec to take his place.

Jerh Collins, who was most recently chief culture officer at Novartis, will join Moderna on Oct. 3 and assume the CTO position on Jan. 1 as Andres makes his transition. Both execs will report directly to Bancel.

It’s all part of what Bancel calls Moderna’s “next phase of growth,” as he attempts to push beyond the company’s reputation as a Covid vaccine company and build up the broader mRNA platform. The team has a few late-stage projects waiting in the wings, including a respiratory syncytial virus (RSV) vaccine program that’s headed for a readout in the next year or so, and a flu program that Bancel is positioning for a potential accelerated approval next year.

Jerh Collins

Bancel said the new hires come as the company preps for “several upcoming new product launches.”

Collins brings nearly 30 years of Novartis experience to the table, where he served a variety of lead production and manufacturing roles. He noted that he’s worked with Andres “for many years,” as the two both held long tenures at Novartis.

“I’m confident that Jerh possesses the mindset and experience to expand our production footprint as we grow globally and internalize more of our production capabilities,” he said in a news release. The company was not immediately available for an interview.

The news comes as the federal government grapples with shortages of the company’s recently authorized bivalent Covid booster shot caused by manufacturing delays over a safety inspection at Catalent’s Indiana plant. The FDA cleared an additional five batches from the plant on Monday after deciding they’re safe for use.

Moderna’s first-gen vaccine, Spikevax, earned the company $17.7 billion last year alone. However, in an effort to raise awareness for the rest of the pipeline, the company undertook a major rebrand in July.

​​“We’re proud of being a Covid company — that was the proof point of our technology,” chief brand officer Kate Cronin told Endpoints News at the time. “But now we have 40-plus programs that we’re studying, and we want the world to know we believe in this technology, and there’s a future beyond Covid.”

That includes a cytomegalovirus (CMV) program, which was among the company’s lead programs before Covid-19 came around. CMV is a type of latent herpes virus, and the most common cause of infection before birth, according to Moderna. The company’s candidate, mRNA-1647, is in Phase III trial to evaluate congenital infection, which is currently enrolling.

Further along is the company’s seasonal flu vaccine, mRNA-1010, which is in a fully enrolled study in the south and is slated for an accelerated approval application next year.

As for RSV, a Phase III trial is “rapidly advancing toward completion,” with a readout expected in the 2022-2023 winter season. Moderna’s also expecting a Phase II readout from its precision cancer vaccine, mRNA-4157, in combination with Keytruda in the fourth quarter of this year.

Combination vaccine trials covering the flu, Covid and RSV should be launched this year as well, Moderna said at a recent investor event. And on the Q2 call, president Stephen Hoge revealed that the company’s been looking into a preclinical monkeypox program which could potentially be ramped up “very quickly.”

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New drug has potential to turn COVID-19 virus against itself

LA JOLLA, CA—A new drug designed by scientists at Scripps Research can turn the COVID-19 virus into a harbinger of its own doom. Credit: Scripps Research…

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LA JOLLA, CA—A new drug designed by scientists at Scripps Research can turn the COVID-19 virus into a harbinger of its own doom.

Credit: Scripps Research

LA JOLLA, CA—A new drug designed by scientists at Scripps Research can turn the COVID-19 virus into a harbinger of its own doom.

The drug, NMT5, described in Nature Chemical Biology on September 29, 2022, coats SARS-CoV-2 with chemicals that can temporarily alter the human ACE2 receptor—the molecule the virus normally latches onto to infect cells. That means that when the virus is near, its path into human cells via the ACE2 receptor is blocked; in the absence of the virus, however, ACE2 can function as usual.

“What’s so neat about this drug is that we’re actually turning the virus against itself,” says senior author Stuart Lipton, MD, PhD, the Step Family Endowed Chair and Scripps Research professor. “We’re arming it with little molecular warheads that end up preventing it from infecting our cells; it’s our revenge on the virus.”

Before the COVID-19 pandemic, Lipton and his colleagues had long been studying variations of the drug memantine, which Lipton developed and patented in the 1990s for treating neurological diseases like Alzheimer’s. While memantine originated from an anti-influenza drug used in the 1960s, clinicians began investigating it for additional diseases after they noticed a woman with Parkinson’s symptoms improved when she took the drug for the flu.

“My team had made these antiviral drugs better for the brain, and when COVID-19 emerged, we wondered whether we had also, in the process, made any of them better antivirals,” says Lipton.

Lipton and his team tested a library of compounds similar to memantine in overall structure but covered with additional pharmacological warheads. They pinpointed the drug candidate designated NMT5 as having two key properties: It could recognize and attach to a pore on the surface of SARS-CoV-2, and it could chemically modify human ACE2 using a fragment of nitroglycerin as the warhead. The group realized this could turn the virus into a delivery vehicle for its own demise.

In the new paper, Lipton’s group characterized and tested NMT5 in isolated cells as well as animals. They showed how NMT5 attaches tightly to SARS-CoV-2 viral particles as the viruses move through the body. Then, they revealed the details of how the drug adds a chemical (similar to nitroglycerin) to certain molecules if it gets close enough. When the virus gets near ACE2 to infect a cell, that translates into NMT5 adding a “nitro group” to the receptor. When ACE2 is modified in this way, its structure temporarily shifts – for about 12 hours – so that the SARS-CoV-2 virus can no longer bind to it to cause infection.

“What’s really beautiful is that this only knocks down availability of ACE2 locally when the virus is coming at it,” says Lipton. “It doesn’t knock down all the function of ACE2 elsewhere in the body, allowing for normal function of this protein.”

In cell culture experiments testing how well the Omicron variant of SARS-CoV-2 can attach to human ACE2 receptors, the drug prevented 95% of viral binding. In hamsters with COVID-19, NMT5 decreased virus levels by 100-fold, eliminated blood vessel damage in the animals’ lungs, and ameliorated inflammation. The drug also showed effectiveness against nearly a dozen other variants of COVID-19, including alpha, beta, gamma and delta strains.

Most anti-viral drugs work by directly blocking part of a virus—which can pressure the virus to evolve resistance to the drug. Since NMT5 is only using the virus as a carrier, the researchers think the drug is likely to be effective against many other variants of SARS-CoV-2.

“We expect this compound would continue to be effective even as new variants emerge, because it doesn’t rely on attacking parts of the virus that commonly mutate,” says Chang-ki Oh, a senior staff scientist and first author of the new paper.

Though they have only studied the compound in animal models, the team is now making a version of the drug to evaluate for human use, while carrying out additional safety and effectiveness trials in animals. This work is being sponsored by the Scripps Center Grant for Antiviral Medicines & Pandemic Preparedness (CAMPP AViDD) from the National Institutes of Health (U19 AI171443).

“These exciting findings suggest a new avenue for drug development that requires drug combinations for effective pandemic preparedness,” says co-author Arnab Chatterjee, PhD.

In addition to Lipton, Oh and Chatterjee, authors of the new paper are Tomohiro Nakamura, Nathan Beutler, Xu Zhang, Juan Piña-Crespo, Maria Talantova, Swagata Ghatak, Dorit Trudler, Lauren N. Carnevale, Scott R. McKercher, Malina A. Bakowski, Jolene K. Diedrich, Amanda J. Roberts, Ashley K. Woods, Victor Chi, Anil K. Gupta, Namir Shaabani, Hejun Liu, Ian A. Wilson, Dennis R. Burton, John R. Yates III and Thomas F. Rogers of Scripps Research; Mia A. Rosenfeld, Fiona L. Kearns, Lorenzo Casalino and Rommie E. Amaro of UCSD; and Cyrus Becker of EuMentis Therapeutics, Inc.

This work was supported in part by grants from the National Institutes of Health (RF1 AG057409, R01 AG056259, R01 DA048882, R35 AG071734 and DP1 DA041722, R01 AG061845, R61 NS122098, RF1 NS123298, UM1 AI144462, P41 GM103533, HOPE T32 Training Grant T32AI007384), the California Institute for Regenerative Medicine (DISC2 COVID19-11811), COVID-19 awards from Fast Grants, and the Bill & Melinda Gates Foundation (OPP1107194, INV-004923).

Lipton is an inventor of patents for the use of memantine and related compounds for neurodegenerative and neurodevelopmental disorders. He is also an inventor of composition of matter patents and use patents for aminoadamantane nitrate compounds like NMT5 in treating COVID-19 and other viral diseases. Lipton is also the scientific founder of EuMentis Therapeutics, Inc., which holds the rights to these drugs.


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