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Covid-19 roundup: Boehringer pulls a drug out of the pipeline for a PhII Covid-19 trial; Novavax delays PhIII trial in US, with PhII data coming Friday

Covid-19 roundup: Boehringer pulls a drug out of the pipeline for a PhII Covid-19 trial; Novavax delays PhIII trial in US, with PhII data coming Friday

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With big questions still hanging over the fate of the vaccines and drugs now in late-stage development for Covid-19, Boehringer Ingelheim is pulling one of its early-stage drugs into a Phase II trial to see if it can help some of the most severely afflicted patients.

Put through a safety study last year, researchers have been intrigued by the potential of BI 764198 — a TRPC6 inhibitor — as a treatment for acute respiratory distress syndrome (ARDS), which can cause immense damage and death for patients exposed to the virus.

Clive Wood

As the pandemic hit, “we started to ask, what are the mechanisms we have in the pipeline, what might help these patients?” says Clive Wood, head of discovery research at Boehringer. That led them to a drug in development for chronic kidney disease, which shares a pathway that could have an impact on the virus.

“We are far from having a clear path to having a clear path to the end of this situation,” says Wood, and that makes it important to recruit 90 patients for the Phase II, with the ability to pivot into a late-stage registration study if it works out.

Even if it doesn’t work out in time for Covid-19, Boehringer’s researchers expect that success could pave the way to other uses in the future. Right now, the only thing they know for certain is they need to see if it works. — John Carroll

Manufacturing delay pushes back the launch of a PhIII at Novavax

Though Novavax $NVAX is near the forefront of the Covid-19 vaccine race, it will be starting its Phase III trial later than anticipated.

The company said Tuesday that its late-stage study in the US has been pushed back to the end of November after delays in upscaling its manufacturing processes. That’s about one month after previously reported timelines.

Meanwhile, trial data from a separate Phase III being conducted in the UK are likely coming sometime “early” in the first quarter, Novavax said, adding that the results from this study “are expected to serve as the basis for global licensure.” Novavax did not elaborate on what that meant nor how they plan to apply for such “licensure” in the US.

Additionally, new Phase II data from the company’s ongoing Phase I/II trial are expected to come Friday. Investors mostly greeted the news warmly, as the company’s shares rose about 3% in Tuesday trading.

While there haven’t been any Covid-19 vaccine approvals or EUAs thus far, there have been a few for treatments. The FDA recently granted approval for Gilead’s remdesivir, marketed as Veklury, in hospitalized patients older than 12. That followed an EUA for the therapy, as well as EUAs for hydroxychloroquine and convalescent plasma. Regulators have since revoked the former’s authorization.

Novavax received a $1.6 billion Warp Speed contract in July and began its UK Phase III study in late September. The biotech is testing a two-shot regimen of its lower, 5 µg dose of protein antigen currently in Phase II, plus a 50 µg Matrix‑M adjuvant. The shots are being administered 21 days apart.

Pfizer currently leads Endpoints News’ Covid-19 vaccine race tracker, with Novavax coming in 8th. — Max Gelman

CBER director promises ‘safe and effective’ vaccine in op-ed

In an effort to shore up trust in the FDA’s ability to authorize a safe and effective vaccine, CBER director Peter Marks broke down the EUA process in a USA Today op-ed. 

“We hope to ensure public confidence in COVID-19 vaccines by being transparent about FDA’s decision-making process,” he wrote. “Whether a vaccine is made available through an EUA or through a traditional approval, FDA will ensure that it is safe and effective.”

Peter Marks

In the roughly 1,000-word piece, Marks promised that an EUA decision will not be rushed. And he explained that the FDA’s minimum recommendation of 50% efficacy is just that — a minimum.

“Of course, it is hoped that the vaccines will prevent a much higher percentage of cases, but the 50% figure establishes the minimum efficacy of a COVID-19 vaccine that FDA could find acceptable,” he said.

The director also mentioned that considerations for an EUA may be different, depending on how a product will be used. For example, if a drug is intended for hospitalized patients who have no other treatment, “the potential benefits may outweigh the risks even if there is uncertainty about effectiveness and there are real, but acceptable, safety concerns,” Marks wrote.

In June, the FDA yanked an EUA for hydroxychloroquine as a Covid-19 treatment, after determining the drug is “unlikely to be effective.” And in September, a panel of experts convened by the NIH concluded that there is a lack of data supporting the safety and efficacy of another coronavirus treatment granted an EUA: convalescent plasma.

In the op-ed, Marks said that wouldn’t be the case for a vaccine:

For a COVID-19 vaccine that could be administered to millions of individuals, including healthy people, FDA will only issue an EUA if a vaccine has demonstrated clear and compelling efficacy in a large well-designed phase 3 clinical trial, much like would be required for a BLA. 

Normally, drug makers take months to analyze data before submitting a BLA, which can be tens of thousands of pages long, according to Marks. “But these are not ‘normal’ times,” he said. “In the United States, we have seen many hundreds of people die every day from COVID-19.”

“With high uptake, COVID-19 vaccines have the potential to save many lives in the United States that may otherwise be lost. And saving as many lives as is possible must be the goal that we strive to achieve together,” he wrote. — Nicole DeFeudis

Sanofi and GSK pledge 200 million vaccine doses

Sanofi and GSK have agreed to give 200 million doses of their vaccine candidate to the COVAX Facility, which is part of a program set up by CEPI, the WHO and Gavi to equitably distribute vaccines around the world.

The idea behind COVAX is to give all participating countries equal access to vaccines, regardless of income level. As of Oct. 14, more than 180 countries had signed agreements to the COVAX Facility, including France and the UK. China joined earlier this month, pledging to make its vaccines a “global public good.” One country notably off the list is the United States.

The Trump administration has refused to join the program. The US has placed an initial $1.95 billion order for 100 million doses of Pfizer’s candidate, with the option to acquire up to 500 million more down the road. And it placed a $1.5 billion order with Moderna for 100 million doses, with an option for another 400 million later. One White House spokesman said the country won’t be “constrained by multilateral organizations influenced by the corrupt World Health Organization and China,” according to a Bloomberg report.

COVAX is hoping to have 2 billion doses available by the end of 2021, “which should be enough to protect high risk and vulnerable people, as well as frontline healthcare workers,” the GAVI website states.

Thomas Triomphe

Sanofi and GSK entered their adjuvanted recombinant protein-based candidate in a Phase I/II study on Sept. 3, and anticipate the first cut of data in early December. The companies are hoping the results support the launch a pivotal Phase III trial before the end of the year. If all goes according to plan, they think a request for approval could come in the first half of 2021.

“The commitment we are announcing today for the COVAX Facility can help us together stand a better chance of bringing the pandemic under control,” Sanofi Pasteur executive VP and global head Thomas Triomphe said in a statement. “This moment also reflects our long-term commitment to global health and ensures our COVID-19 vaccines are affordable and accessible to those most at risk, everywhere in the world.” — Nicole DeFeudis

Vaccinologist Paul Offit calls for more efficacy data 

In the next couple months, drug makers will likely submit EUA applications for Covid-19 vaccines, renowned vaccinologist Paul Offit predicts.

This could come at the beginning of a “twindemic” — parallel flu and coronavirus outbreaks, he added. The question is, what will be required for emergency authorization?

“Permission is being given to vaccinate 150 million Americans essentially, which is obviously something we’ve never dealt with before,” Offit, director of the Children’s Hospital of Philadelphia’s Vaccine Education Center and inventor of the rotavirus vaccine, said in a JAMA Network interview.

Paul Offit

“How much uncertainty are we willing to live with knowing that we’re facing a virus that’s brought us to our knees?” he asked later.

Offit said he’s concerned the public will see emergency authorization as “flimsy,” or based on a lack of evidence, after what happened with hydroxychloroquine and the “convalescent plasma fiasco.”

“I think where the rubber’s going to meet the road here is how we handle these interim analyses,” he said in the interview.

Pfizer and BioNTech, currently in the lead for an EUA, announced in their trial protocol that their first interim analysis would occur when 32 participants are infected. Moderna will hold its first interim analysis at 53 events. And AstraZeneca is planning to conduct an analysis when 75 patients get sick. Researchers would then compare how many infections occurred in the vaccine arm, versus the placebo arm.

“I’d like to think that we’re going to be really loathe to approve this or to recommend approval through emergency use authorization with just 34 or 60 participants getting sick,” Offit said.

In NIH ACTIV trials, statisticians wanted to see 147 infections if the vaccine was administered in a 2:1 ratio to placebo, or 160 infections in a 1:1 scenario, Offit said. “That’s where I’m coming from,” he added.

“If dreams could come true, all I ask is this: Let’s have at least 150 participants that got sick,” Offit said. “That’s all I ask.” — Nicole DeFeudis

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Are Voters Recoiling Against Disorder?

Are Voters Recoiling Against Disorder?

Authored by Michael Barone via The Epoch Times (emphasis ours),

The headlines coming out of the Super…

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Are Voters Recoiling Against Disorder?

Authored by Michael Barone via The Epoch Times (emphasis ours),

The headlines coming out of the Super Tuesday primaries have got it right. Barring cataclysmic changes, Donald Trump and Joe Biden will be the Republican and Democratic nominees for president in 2024.

(Left) President Joe Biden delivers remarks on canceling student debt at Culver City Julian Dixon Library in Culver City, Calif., on Feb. 21, 2024. (Right) Republican presidential candidate and former U.S. President Donald Trump stands on stage during a campaign event at Big League Dreams Las Vegas in Las Vegas, Nev., on Jan. 27, 2024. (Mario Tama/Getty Images; David Becker/Getty Images)

With Nikki Haley’s withdrawal, there will be no more significantly contested primaries or caucuses—the earliest both parties’ races have been over since something like the current primary-dominated system was put in place in 1972.

The primary results have spotlighted some of both nominees’ weaknesses.

Donald Trump lost high-income, high-educated constituencies, including the entire metro area—aka the Swamp. Many but by no means all Haley votes there were cast by Biden Democrats. Mr. Trump can’t afford to lose too many of the others in target states like Pennsylvania and Michigan.

Majorities and large minorities of voters in overwhelmingly Latino counties in Texas’s Rio Grande Valley and some in Houston voted against Joe Biden, and even more against Senate nominee Rep. Colin Allred (D-Texas).

Returns from Hispanic precincts in New Hampshire and Massachusetts show the same thing. Mr. Biden can’t afford to lose too many Latino votes in target states like Arizona and Georgia.

When Mr. Trump rode down that escalator in 2015, commentators assumed he’d repel Latinos. Instead, Latino voters nationally, and especially the closest eyewitnesses of Biden’s open-border policy, have been trending heavily Republican.

High-income liberal Democrats may sport lawn signs proclaiming, “In this house, we believe ... no human is illegal.” The logical consequence of that belief is an open border. But modest-income folks in border counties know that flows of illegal immigrants result in disorder, disease, and crime.

There is plenty of impatience with increased disorder in election returns below the presidential level. Consider Los Angeles County, America’s largest county, with nearly 10 million people, more people than 40 of the 50 states. It voted 71 percent for Mr. Biden in 2020.

Current returns show county District Attorney George Gascon winning only 21 percent of the vote in the nonpartisan primary. He’ll apparently face Republican Nathan Hochman, a critic of his liberal policies, in November.

Gascon, elected after the May 2020 death of counterfeit-passing suspect George Floyd in Minneapolis, is one of many county prosecutors supported by billionaire George Soros. His policies include not charging juveniles as adults, not seeking higher penalties for gang membership or use of firearms, and bringing fewer misdemeanor cases.

The predictable result has been increased car thefts, burglaries, and personal robberies. Some 120 assistant district attorneys have left the office, and there’s a backlog of 10,000 unprosecuted cases.

More than a dozen other Soros-backed and similarly liberal prosecutors have faced strong opposition or have left office.

St. Louis prosecutor Kim Gardner resigned last May amid lawsuits seeking her removal, Milwaukee’s John Chisholm retired in January, and Baltimore’s Marilyn Mosby was defeated in July 2022 and convicted of perjury in September 2023. Last November, Loudoun County, Virginia, voters (62 percent Biden) ousted liberal Buta Biberaj, who declined to prosecute a transgender student for assault, and in June 2022 voters in San Francisco (85 percent Biden) recalled famed radical Chesa Boudin.

Similarly, this Tuesday, voters in San Francisco passed ballot measures strengthening police powers and requiring treatment of drug-addicted welfare recipients.

In retrospect, it appears the Floyd video, appearing after three months of COVID-19 confinement, sparked a frenzied, even crazed reaction, especially among the highly educated and articulate. One fatal incident was seen as proof that America’s “systemic racism” was worse than ever and that police forces should be defunded and perhaps abolished.

2020 was “the year America went crazy,” I wrote in January 2021, a year in which police funding was actually cut by Democrats in New York, Los Angeles, San Francisco, Seattle, and Denver. A year in which young New York Times (NYT) staffers claimed they were endangered by the publication of Sen. Tom Cotton’s (R-Ark.) opinion article advocating calling in military forces if necessary to stop rioting, as had been done in Detroit in 1967 and Los Angeles in 1992. A craven NYT publisher even fired the editorial page editor for running the article.

Evidence of visible and tangible discontent with increasing violence and its consequences—barren and locked shelves in Manhattan chain drugstores, skyrocketing carjackings in Washington, D.C.—is as unmistakable in polls and election results as it is in daily life in large metropolitan areas. Maybe 2024 will turn out to be the year even liberal America stopped acting crazy.

Chaos and disorder work against incumbents, as they did in 1968 when Democrats saw their party’s popular vote fall from 61 percent to 43 percent.

Views expressed in this article are opinions of the author and do not necessarily reflect the views of The Epoch Times or ZeroHedge.

Tyler Durden Sat, 03/09/2024 - 23:20

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Veterans Affairs Kept COVID-19 Vaccine Mandate In Place Without Evidence

Veterans Affairs Kept COVID-19 Vaccine Mandate In Place Without Evidence

Authored by Zachary Stieber via The Epoch Times (emphasis ours),

The…

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Veterans Affairs Kept COVID-19 Vaccine Mandate In Place Without Evidence

Authored by Zachary Stieber via The Epoch Times (emphasis ours),

The U.S. Department of Veterans Affairs (VA) reviewed no data when deciding in 2023 to keep its COVID-19 vaccine mandate in place.

Doses of a COVID-19 vaccine in Washington in a file image. (Jacquelyn Martin/Pool/AFP via Getty Images)

VA Secretary Denis McDonough said on May 1, 2023, that the end of many other federal mandates “will not impact current policies at the Department of Veterans Affairs.”

He said the mandate was remaining for VA health care personnel “to ensure the safety of veterans and our colleagues.”

Mr. McDonough did not cite any studies or other data. A VA spokesperson declined to provide any data that was reviewed when deciding not to rescind the mandate. The Epoch Times submitted a Freedom of Information Act for “all documents outlining which data was relied upon when establishing the mandate when deciding to keep the mandate in place.”

The agency searched for such data and did not find any.

The VA does not even attempt to justify its policies with science, because it can’t,” Leslie Manookian, president and founder of the Health Freedom Defense Fund, told The Epoch Times.

“The VA just trusts that the process and cost of challenging its unfounded policies is so onerous, most people are dissuaded from even trying,” she added.

The VA’s mandate remains in place to this day.

The VA’s website claims that vaccines “help protect you from getting severe illness” and “offer good protection against most COVID-19 variants,” pointing in part to observational data from the U.S. Centers for Disease Control and Prevention (CDC) that estimate the vaccines provide poor protection against symptomatic infection and transient shielding against hospitalization.

There have also been increasing concerns among outside scientists about confirmed side effects like heart inflammation—the VA hid a safety signal it detected for the inflammation—and possible side effects such as tinnitus, which shift the benefit-risk calculus.

President Joe Biden imposed a slate of COVID-19 vaccine mandates in 2021. The VA was the first federal agency to implement a mandate.

President Biden rescinded the mandates in May 2023, citing a drop in COVID-19 cases and hospitalizations. His administration maintains the choice to require vaccines was the right one and saved lives.

“Our administration’s vaccination requirements helped ensure the safety of workers in critical workforces including those in the healthcare and education sectors, protecting themselves and the populations they serve, and strengthening their ability to provide services without disruptions to operations,” the White House said.

Some experts said requiring vaccination meant many younger people were forced to get a vaccine despite the risks potentially outweighing the benefits, leaving fewer doses for older adults.

By mandating the vaccines to younger people and those with natural immunity from having had COVID, older people in the U.S. and other countries did not have access to them, and many people might have died because of that,” Martin Kulldorff, a professor of medicine on leave from Harvard Medical School, told The Epoch Times previously.

The VA was one of just a handful of agencies to keep its mandate in place following the removal of many federal mandates.

“At this time, the vaccine requirement will remain in effect for VA health care personnel, including VA psychologists, pharmacists, social workers, nursing assistants, physical therapists, respiratory therapists, peer specialists, medical support assistants, engineers, housekeepers, and other clinical, administrative, and infrastructure support employees,” Mr. McDonough wrote to VA employees at the time.

This also includes VA volunteers and contractors. Effectively, this means that any Veterans Health Administration (VHA) employee, volunteer, or contractor who works in VHA facilities, visits VHA facilities, or provides direct care to those we serve will still be subject to the vaccine requirement at this time,” he said. “We continue to monitor and discuss this requirement, and we will provide more information about the vaccination requirements for VA health care employees soon. As always, we will process requests for vaccination exceptions in accordance with applicable laws, regulations, and policies.”

The version of the shots cleared in the fall of 2022, and available through the fall of 2023, did not have any clinical trial data supporting them.

A new version was approved in the fall of 2023 because there were indications that the shots not only offered temporary protection but also that the level of protection was lower than what was observed during earlier stages of the pandemic.

Ms. Manookian, whose group has challenged several of the federal mandates, said that the mandate “illustrates the dangers of the administrative state and how these federal agencies have become a law unto themselves.”

Tyler Durden Sat, 03/09/2024 - 22:10

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Low Iron Levels In Blood Could Trigger Long COVID: Study

Low Iron Levels In Blood Could Trigger Long COVID: Study

Authored by Amie Dahnke via The Epoch Times (emphasis ours),

People with inadequate…

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Low Iron Levels In Blood Could Trigger Long COVID: Study

Authored by Amie Dahnke via The Epoch Times (emphasis ours),

People with inadequate iron levels in their blood due to a COVID-19 infection could be at greater risk of long COVID.

(Shutterstock)

A new study indicates that problems with iron levels in the bloodstream likely trigger chronic inflammation and other conditions associated with the post-COVID phenomenon. The findings, published on March 1 in Nature Immunology, could offer new ways to treat or prevent the condition.

Long COVID Patients Have Low Iron Levels

Researchers at the University of Cambridge pinpointed low iron as a potential link to long-COVID symptoms thanks to a study they initiated shortly after the start of the pandemic. They recruited people who tested positive for the virus to provide blood samples for analysis over a year, which allowed the researchers to look for post-infection changes in the blood. The researchers looked at 214 samples and found that 45 percent of patients reported symptoms of long COVID that lasted between three and 10 months.

In analyzing the blood samples, the research team noticed that people experiencing long COVID had low iron levels, contributing to anemia and low red blood cell production, just two weeks after they were diagnosed with COVID-19. This was true for patients regardless of age, sex, or the initial severity of their infection.

According to one of the study co-authors, the removal of iron from the bloodstream is a natural process and defense mechanism of the body.

But it can jeopardize a person’s recovery.

When the body has an infection, it responds by removing iron from the bloodstream. This protects us from potentially lethal bacteria that capture the iron in the bloodstream and grow rapidly. It’s an evolutionary response that redistributes iron in the body, and the blood plasma becomes an iron desert,” University of Oxford professor Hal Drakesmith said in a press release. “However, if this goes on for a long time, there is less iron for red blood cells, so oxygen is transported less efficiently affecting metabolism and energy production, and for white blood cells, which need iron to work properly. The protective mechanism ends up becoming a problem.”

The research team believes that consistently low iron levels could explain why individuals with long COVID continue to experience fatigue and difficulty exercising. As such, the researchers suggested iron supplementation to help regulate and prevent the often debilitating symptoms associated with long COVID.

It isn’t necessarily the case that individuals don’t have enough iron in their body, it’s just that it’s trapped in the wrong place,” Aimee Hanson, a postdoctoral researcher at the University of Cambridge who worked on the study, said in the press release. “What we need is a way to remobilize the iron and pull it back into the bloodstream, where it becomes more useful to the red blood cells.”

The research team pointed out that iron supplementation isn’t always straightforward. Achieving the right level of iron varies from person to person. Too much iron can cause stomach issues, ranging from constipation, nausea, and abdominal pain to gastritis and gastric lesions.

1 in 5 Still Affected by Long COVID

COVID-19 has affected nearly 40 percent of Americans, with one in five of those still suffering from symptoms of long COVID, according to the U.S. Centers for Disease Control and Prevention (CDC). Long COVID is marked by health issues that continue at least four weeks after an individual was initially diagnosed with COVID-19. Symptoms can last for days, weeks, months, or years and may include fatigue, cough or chest pain, headache, brain fog, depression or anxiety, digestive issues, and joint or muscle pain.

Tyler Durden Sat, 03/09/2024 - 12:50

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