U.S. Supreme Court backs religious groups over New York virus curbs

 The U.S. Supreme Court late on Wednesday backed Christian and Jewish houses of worship challenging New York state’s latest restrictions in novel coronavirus hot spots.

The court on a 5-4 vote granted requests made by the Roman Catholic Diocese of Brooklyn and two Orthodox Jewish congregations.

The order marked one of the first consequential actions on the court of President Donald Trump’s new appointee, conservative Justice Amy Coney Barrett, who cast a deciding vote in favor of the religious groups. Conservative Chief Justice John Roberts dissented along with the court’s three liberals.

An Oct. 6 decision by New York Governor Andrew Cuomo shut down non-essential businesses in targeted areas where infections have spiked, including some Brooklyn neighborhoods. It limited gatherings at religious institutions to 10 people in some areas and 25 in others.

The houses of worship say that the limits violated religious freedoms protected by the U.S. Constitution’s First Amendment, and that their facilities were singled out for more stringent restrictions than essential businesses, such as food stores. The Orthodox congregations Agudath Israel of Kew Garden Hills and Agudath Israel of Madison, as well as nationwide Orthodox Jewish group Agudath Israel of America.

A federal judge in Brooklyn rejected separate requests made by the religious groups on Oct. 9. The New York-based 2nd U.S. Circuit Court of Appeals declined emergency requests filed by both sets of challengers on Nov. 9.

In two previous cases this year, the court on 5-4 votes turned away similar requests by churches in Nevada and California.

Those votes occurred before the death of liberal Justice Ruth Bader Ginsburg and saw her and her three liberal colleagues joined by Roberts in the majority.

https://www.reuters.com/article/us-health-coronavirus-usa-court/u-s-supreme-court-backs-religious-groups-over-new-york-virus-curbs-idUSKBN2860CK

Why Is WHO Second-Guessing COVID-19 Drug?

 In a baffling decision that could harm the poorest patients, the World Health Organization (WHO) told global physicians Friday not to prescribe remdesivir – even though it is the only COVID-19 treatment approved by the world’s top pharmaceutical regulator, the U.S. Food & Drug Administration (FDA).

The WHO, under fire for its slow start against the global pandemic, decided to shun the FDA and base a decision on its own study. That study, still incomplete, used methods inferior to the National Institutes of Health (NIH) trial that confirmed the efficacy and safety of the COVID drug, now called in many countries by its brand name Veklury.

While the WHO recommendation is not binding, it is part of a “living guideline” project giving advice to doctors. The decision probably will not affect the use of Veklury in the U.S. and other developed countries, but it could prevent the medicine from getting to people who need it in low-income nations.

The FDA granted Veklury emergency use authorization in May and final approval on Oct. 22 as the sole therapeutic authorized for patients with COVID-19. The European Medicines Agency and Japan’s Pharmaceuticals and Medical Devices Agency have granted approval as well.

Veklury has become accepted as the standard of care for people with serious cases of coronavirus, and 2 million treatment courses will be produced this year with several million more in 2021, if needed. The European Commission signed a Joint Procurement Agreement on Oct. 8 with Gilead Sciences, the Silicon Valley biotech that developed the drug, for up to 500,000 treatment courses for 37 countries. Gilead made 650,000 treatment courses – about 150,000 of them free – available to the federal government for U.S. distribution. The company now sells the medicine directly to hospitals.

The big question is why the WHO decided to conduct a study that came up with this controversial recommendation. The answer lies in the criticism the organization has received over the past year that led to the U.S. serving notice it will withdraw from the WHO in July 2021. Officials in other countries, including Japan and France, have also condemned WHO’s deference to China and delay early in the pandemic.

“Scientists and health experts,” said a New York Times article in July, have “criticized the WHO for being slow to update its guidance and keep step with science as understanding of the virus rapidly evolves.”

In trying to recover from this criticism, the WHO, despite its limited experience in running pharmaceutical trials, is clearly trying to reach for new relevance in the pandemic by becoming a drug researcher and arbiter. But that attempt is backfiring. Its research pales in comparison to the NIH trial on which the FDA relied and which was complemented by two other studies.

The randomized, placebo-controlled, double-blind clinical trial – the gold standard for drug evaluation – was conducted by NIH’s Institute of Allergy and Infectious Diseases. In contrast to the open-label WHO trial, the 1,062 hospitalized patients did not know whether they were getting remdesivir or a medicine with no therapeutic value.

The NIH study, reported in a peer-reviewed article in the New England Journal of Medicine on Nov. 5, found that, with remdesivir, the median time to recovery was five days shorter than with the placebo group, “a statistically significant difference,” said the FDA. The article concluded the drug was “beneficial in the treatment of Covid-19.”

Based on cost alone, the results were highly significant. According to a study released this month by FAIR Health, a non-profit, the cost of a COVID hospital stay of 11 to 15 days for a patient over 60 years old was $152,388 while the cost of a stay of 6 to 10 days was $89,973 – a difference of more than $60,000 for a drug which, according to the Department of Health and Human Services, has a cost of approximately $3,200 for a full five-day course.

By comparison with the NIH study, the WHO’s trial, called Solidarity, tracked patients in 405 hospitals in 30 countries “in record time” without controls. WHO concluded that all four drugs studied, including remdesivir, “appeared to have little or no effect,” but it called the finding “conditional” and said that “more research is needed.”

The WHO recommendation leaves many developing nations in a bind. Gilead has issued licenses, free of royalty charges for the duration of the epidemic to manufacture remdesivir in India, Pakistan and Egypt for distribution to 127 mainly low-to-middle-income countries. Many of those nations have limited regulatory capacity and depend on WHO recommendations or on donations of WHO pre-qualified drugs distributed by international global health organizations. Without remdesivir, they have few, if any, effective treatment alternatives for COVID patients.

Rather than second-guessing the best drug evaluators in the world, the WHO should stick to what it was created to do. As the organization’s website says, “Our primary role is to direct and coordinate international health.” That’s a big enough job in itself, especially during the worst pandemic in a century.

James K. Glassman, former Under Secretary of State for Public Diplomacy, is an advisor to health care companies and non-profits.

https://www.realclearhealth.com/articles/2020/11/23/why_is_who_second-guessing_covid-19_drug_111140.html

Efficacy of Nicotine Patches in SARS-CoV2 (COVID-19) Infection in Intensive Care

 ClinicalTrials.gov Identifier: NCT04598594

Sponsor:

Assistance Publique - Hôpitaux de Paris

See Contacts and Locations

Brief Summary:

There is currently no known treatment for COVID19. Active smokers are infrequent among patients with COVID-19 which has led our team to hypothesize that nicotine is responsible for this protective effect via the nicotinic acetylcholine receptor (nAChR). In fact, nAChR possess the ability to modulate ACE2 expression, the cellular doorway for SARS-CoV2. nAChR modulation by the virus would be responsible for the numerous clinical signs observed in COVID-19, including the cytokine storm manifested in intensive care hyperinflammatory patients.

Based on epidemiological data and experimental data from scientific literature, our team hypothesize that nicotine could inhibit the penetration and propagation of SARS-CoV2. Our team also claim that nicotine could attenuate the hyperinflammatory response and cytokine storm leading to acute respiratory failure and a probable multi-organ failure associated with COVID19.

Condition or disease	Intervention/treatment	Phase
Covid19SARS-Associated Coronavirus as Cause of Disease Classified Elsewhere	Drug: Patch, NicotineDrug: Patch, Placebo	Phase 3

Estimated Study Start Date  :	November 2020
Estimated Primary Completion Date  :	September 2021
Estimated Study Completion Date  :	November 2021 https://clinicaltrials.gov/ct2/show/NCT04598594

FDA OKs Y-mAbs' neuroblastoma treatment

 

• Y-mAbs Therapeutics (NASDAQ:YMAB) +14.3% after-hours as the Food and Drug Administration grants accelerated approval of its Danyelza (naxitamab) cancer treatment for patients with relapsed or refractory high-risk neuroblastoma in the bone or bone marrow.
• Y-mAbs says the FDA approval was supported by clinical evidence from two pivotal studies in patients with high-risk neuroblastoma with refractory or relapsed disease.
• The company expects Danyelza will be available for use in the U.S. "in the coming weeks."
• The approval was expected, and the stock price recently hit a 52-week intraday high.
• https://seekingalpha.com/news/3639563-fda-oks-y-mabs-neuroblastoma-treatment

AstraZeneca Covid Vaccine Data Aren't Up to Snuff

 THE MAKERS OF a third coronavirus vaccine announced positive results in clinical trials on Monday, setting off yet another round of excited news reports. This one, produced by a partnership between a University of Oxford research institute, its spinout company Vaccitech, and the pharmaceutical company AstraZeneca, does not need to be stored at freezing temperatures and would be cheaper and easier to produce than the high-efficacy vaccines produced by BioNTech-Pfizer and Moderna. Indeed, according to an initial write-up in The New York Times, Oxford-AstraZeneca’s is “expected to be relied upon heavily across the globe, to help curb a pandemic that has killed more than 1.3 million people.”

Sounds like great news, right? Monday’s press release from AstraZeneca presents “convincing evidence that [the vaccine] works,” said Science. But not everyone has been convinced. The price of AstraZeneca’s shares actually dropped on the news, and an analysis from an investment bank concluded, “We believe that this product will never be licensed in the US.” Over at STAT News, Anthony Fauci cautioned that we’ll need to see more data before coming to a conclusion. The skeptics have strong reasons to be concerned: This week’s “promising” results are nothing like the others that we’ve been hearing about in November—and the claims that have been drawn from them are based on very shaky science.

The problems start with the fact that Monday’s announcement did not present results from a single, large-scale, Phase 3 clinical trial, as was the case for earlier bulletins about the BNT-Pfizer and Moderna vaccines. Instead, Oxford-AstraZeneca’s data came out of two separate studies: one in the UK that began in May, and another in Brazil, which got started at the end of June. These two studies were substantially different from one another: They didn’t have standardized dosing schemes across the trials, for one thing, nor did they provide the same “control” injections to volunteers who were not getting the experimental Covid vaccine. The fact that they may have had to combine data from two trials in order to get a strong enough result raises the first red flag.

Consider that leading vaccine makers—including AstraZeneca—issued a scientific-rigor-and-integrity pledge back in September, in which they promised to submit their products for approval or emergency use authorization only “after demonstrating safety and efficacy through a Phase 3 clinical study that is designed and conducted to meet requirements of expert regulatory authorities such as FDA.” Note the wording here: These companies did not suggest that they might claim to have demonstrated efficacy through multiple, distinct clinical studies, combined together to get enough data. They said they would use a Phase 3 study—as in, one big one. Yet AstraZeneca has already applied on the basis of this data for approval in Canada, and has plans to do the same in Britain, Europe and Brazil. The company also says it will use the data to apply for emergency use authorization in the US.

The Food and Drug Administration’s guidance for Covid-19 vaccines does allow for emergency use authorization based on interim analyses, but the same document says this must be supported by a minimum level of vaccine efficacy “for a placebo-controlled efficacy trial.” Again: it refers to a trial. That is exactly what BNT-Pfizer and Moderna did. Both released the FDA-approved blueprints for their trials—called trial protocols—weeks ahead of time, with details of the calculations and statistical rules that they’d use to determine when to perform an interim analysis and how much certainty could be attached to those results. When BNT-Pfizer’s discussions with the FDA led to changes in this plan, BNT-Pfizer explained why, and released an updated protocol. That’s scientific rigor, and it matters a lot. When a vaccine-maker specifies the rules of the game before the results start coming in, we can check their work and be confident in what they tell us at the end. We can make sure they haven’t cherry-picked the data.

How did Oxford-AstraZeneca end up with this patched-together analysis instead of data from a single, large trial?

The Oxford-AstraZeneca story is very different, though. Presumably, neither of the two trials from which they combined data could have provided a clear answer on the vaccine’s efficacy on its own. To make things worse, Oxford-AstraZeneca reported only the results for certain subgroups of people within each one. (For perspective on this: The two subgroups chosen leave out perhaps half the people in the Brazilian trial.) Meanwhile, one of their key claims is that giving half a dose of the vaccine on the first injection, followed by a standard dose on the second one, led to better outcomes—but neither of these trials had been designed to test this hypothesis. In fact, it’s since emerged that the half-dose/full-dose option started out as a mistake, and one that was only caught when some people in the study didn’t have the usual high rate of adverse effects.

There were other dosing issues, too, that haven’t been explained even though dosing is the centerpiece of the press release. There are many different regimens in these trials—the UK study has more than two dozen arms, meaning the volunteers were divided into that many groups according to age and how much of the vaccine would be administered and when. The doses are measured by the number of altered viral particles they contain, and the developers decided that the standard dose would be 5 x 1010 viral particles. But for many of those arms in the UK trial—as well as everyone who got the vaccine in the Brazilian trial—publicly available trial information shows that the standard dose could be between 3.5 and 6.5 × 1010 viral particles. The lower end of that range isn’t far off from a half-dose.

How did Oxford-AstraZeneca end up with this patched-together analysis instead of data from a single, large trial? After all, this vaccine went into Phase 3 testing before either BNT-PFizer’s or Moderna’s did. But in the UK, where that testing started, the Covid-19 outbreak happened to be receding. That meant results would be coming in very slowly.

A month later, a second Phase 3 trial for the vaccine started in Brazil. That one was for healthcare workers, for whom the risk of being exposed to Covid was far higher than it was for the people in the UK trial. But the two trials had other substantive differences. In the UK, for example, the volunteers who did not get the experimental Covid vaccine were injected with meningococcal vaccine; in Brazil, those in the comparison group were given a saline injection as a placebo.

Meanwhile, BNT-Pfizer and Moderna began Phase 3 trials for their coronavirus vaccines on the same day in July: Both planned to include 30,000 volunteers at the time, and both trial plans were approved by the FDA. Oxford-AstraZeneca then announced they, too, would run a 30,000-person trial in the US.

But that research on the Oxford-AstraZeneca vaccine quickly fell behind the others’. The US trial was approved by the FDA, but it didn’t start recruiting people until the end of August; and just a week later, it was put on hold so the FDA could investigate a serious adverse event in the UK trial. It wasn’t clear what caused the volunteer to get sick, but the FDA did not give the all-clear for Oxford-AstraZeneca’s US trial to resume until Oct. 23. By then the protocol for the trial had been publicly released. It says the plan is to inject the vaccine in two standard doses, a month apart; and two people will be vaccinated for every one who gets a placebo saline injection.

So here we are at the end of November. BNT-Pfizer and Moderna have offered up a masterclass in how to do major vaccine trials quickly in a pandemic, while Oxford-AstraZeneca has, for the moment, only an assortment of smaller ones ready to look at.

https://www.wired.com/story/the-astrazeneca-covid-vaccine-data-isnt-up-to-snuff/

‘Essential workers’ likely to get earlier access to Covid-19 vaccine

 

Essential workers are likely to move ahead of adults 65 and older and people with high-risk medical conditions when the Centers for Disease Control and Prevention signs off on Covid-19 vaccine priority lists, coming after health care workers and people living in long-term care facilities, a meeting of an expert advisory panel made clear Monday.

The intention is to bring many people of color closer to the front of the vaccine priority line — should they want to be vaccinated — in recognition of the fact that the pandemic has disproportionately hit Black and Latino communities.

There was no formal vote by the members of the Advisory Committee on Immunization Practices, a group of outside experts that makes recommendations to the CDC on use of vaccines.

But when asked how they felt about moving essential workers closer to the front of the line, there was clear support for the proposal.

“These essential workers are out there putting themselves at risk to allow the rest of us to socially distance. And they come from disadvantaged situations, they come from disadvantaged communities,” said Beth Bell, a global health expert from the University of Washington who is on ACIP and chairs its Covid-19 work group studying the vaccines.

Bell acknowledged people of color may not wish to be vaccinated early or even ever; polling suggests these communities distrust Covid vaccines even more than the American population in general. But principles of equity require addressing the risks people deemed essential workers are facing in the pandemic.

“We need to provide them with the opportunity early on in the process,” she said. “This is an important message to be sending.”

Essential workers include people who work in meat packing plants and other food processing facilities, in municipal wastewater management operations, and in transport. It also includes police and firefighters and, in the current iteration of the ACIP’s plan, teachers. The CDC estimates there are roughly 87 million people in jobs designated as essential services.

An agency within the Department of Homeland Security known as the Cybersecurity and Infrastructure Security Agency, or CISA, is responsible for designating which jobs are essential services. At the end of the day, however, state, territorial, and tribal authorities will interpret the recommendations and have leeway in who they deem to be essential.

Though people from racial and ethnic minorities make up 40% of the American population, they account for nearly 60% of Covid cases and 50% of the Covid deaths in this country, according to CDC data. Agency data also show that Black people make up about 38% of essential workers, compared to 27% for both white and Hispanic people. Black people also more commonly work in jobs that expose them to SARS-CoV-2, the virus that causes Covid-19.

“These workers are essential. They’re fundamental to our response to Covid. And they’re at risk because they work in close proximity to others,” said Henry Bernstein, chief of pediatrics at North Shore University Hospital.

Robert Atmar, an infectious diseases professor at Baylor College of Medicine, said he too favored the plan, noting that essential workers have less opportunity to lower their risk of being exposed to SARS-2 than adults over 65.

Final decisions on who should get priority access to Covid vaccines will be made after the Food and Drug Administration authorizes them under its emergency use authorization protocol.

A vaccine developed by Pfizer and BioNTech is expected to receive an EUA shortly after the FDA’s advisory committee, the Vaccine and Related Biological Products Advisory Committee, meets on Dec. 10. Consideration of a vaccine developed by Moderna vaccine will occur at a Dec. 17 VRBPAC meeting.

Once the FDA clears the vaccines for use, the ACIP will meet and issue recommendations on the populations that should be eligible to be vaccinated. CDC Director Robert Redfield is expected to sign off on ACIP’s recommendations immediately after they are made, clearing the way for vaccination efforts to begin across the country.

https://www.statnews.com/2020/11/23/essential-workers-likely-to-get-earlier-access-to-covid-19-vaccine/

NIH 4th iteration of COVID-19 treatment trial underway

 The National Institute of Allergy and Infectious Diseases (NIAID), one of the National Institutes of Health, today announced that the fourth iteration of the Adaptive COVID-19 Treatment Trial (ACTT-4) has begun to enroll hospitalized adults with coronavirus disease 2019 (COVID-19) who require supplemental oxygen. The NIAID-sponsored trial will enroll up to 1,500 patients at approximately 100 sites in the United States and other countries.

Participants will be assigned at random to one of two treatment arms of equal size. One group will receive both dexamethasone, a corticosteroid available as a generic drug, and remdesivir, a broad-spectrum antiviral discovered and developed by Gilead Sciences, Inc., of Foster City, California. Remdesivir, also known as Veklury, was recently approved by the U.S. Food and Drug Administration for the treatment of COVID-19 in hospitalized patients aged 12 years and older. The second group will receive remdesivir and baricitinib (brand name Olumiant), a modulator of inflammation that is approved by FDA to treat certain adult patients with moderate to severe rheumatoid arthritis. It was discovered by Incyte and licensed to Eli Lilly and Company, Indianapolis, Indiana. On November 19, FDA granted Emergency Use Authorization (EUA) for baricitinib in combination with remdesivir to treat suspected or laboratory confirmed COVID-19 in hospitalized patients aged 2 years and older who require supplemental oxygen, invasive mechanical ventilation, or extracorporeal membrane oxygenation.

The trial is blinded for the dexamethasone and baricitinib components, meaning investigators and participants will not know who is receiving dexamethasone and who is receiving baricitinib. Dexamethasone is administered by intravenous (IV) infusion, and baricitinib is a tablet taken orally. Therefore, one group will receive oral baricitinib tablets and an IV placebo, and the other group will receive IV dexamethasone and oral placebo tablets. All participants will receive intravenous remdesivir.

ACTT-1 began in February and tested remdesivir compared to placebo in hospitalized adult COVID-19 patients. Interim results, published in May, showed that remdesivir shortened the time to recovery. The ACTT-1 final results(link is external) were published in the New England Journal of Medicine on November 5.

Baricitinib was tested in combination with remdesivir in ACTT-2, which enrolled 1,033 adults hospitalized with COVID-19. The primary results of this study(link is external) were announced by Lilly in September, and peer-reviewed results are forthcoming. ACTT-2 findings indicated that the combination of baricitinib and remdesivir shortened the time to recovery relative to treatment with a placebo and remdesivir. The EUA of baricitinib was based, in part, on the FDA’s review of the data from the ACTT-2 trial.

Dexamethasone was evaluated in the global Randomized Evaluation of COVID-19 Therapy (RECOVERY) trial sponsored by the University of Oxford. Trial results showed that patients receiving dexamethasone demonstrated a lower mortality rate compared with patients receiving usual care.

To date, dexamethasone and baricitinib are the only two therapies that reduce inflammation that have demonstrated efficacy for the treatment of hospitalized adults with COVID-19 in large, randomized clinical trials. However, the differences in study populations, mortality rates and endpoint data collected in the ACTT-2 and RECOVERY trials make it difficult to make firm conclusions about the value of the interventions in various patient populations. ACTT-4 aims to determine whether baricitinib or dexamethasone, when administered with remdesivir, is more effective at preventing hospitalized adults on supplemental oxygen from progressing to requiring mechanical ventilation or death, among other outcomes, or if they are similar.

Investigators will assess participants’ clinical status daily using an eight-point ordinal scale ranging from a return to baseline pre-COVID-19 status and not hospitalized, to death. If discharged from the hospital, clinical status data will be collected during outpatient visits on days 15, 22, 29 and 60. The trial will evaluate the difference in the proportion of participants surviving without requiring invasive mechanical ventilation between the two treatment arms. A key secondary goal is to compare overall clinical status at day 15 in each group by comparing differences in the distribution of the eight-point ordinal scale in each group.

The trial is expected to take approximately three to four months to fully enroll. For more information about the trial, please visit clinicaltrials.gov and search identifier NCT04640168.

https://www.nih.gov/news-events/news-releases/fourth-iteration-covid-19-treatment-trial-underway