FDA begins court-mandated release of thousands of pages on Pfizer Covid vaccine review

 A court loss for the FDA in a Texas district court means the agency on Tuesday began to release a massive trove of hundreds of thousands of documents related to its review of Pfizer’s safe and effective Covid-19 vaccine.

But what exactly will be uncovered in each batch of released documents is anyone’s guess.

The nonprofit that won the court case, known as the Public Health and Medical Professionals for Transparency, promptly released the Pfizer documents on its website this week but did not offer any sort of organization or explanation of what they show.

FDA loses FOIA suit over Pfizer vaccine documents, must release 55,000 pages per month

Some of the documents, like one labeled as a priority review request, includes more than 100 pages worth of anonymous safety-related tables of data. Or another table of unidentified participants’ gender, age and BMI.

Other documents are typical for any drug or vaccine application. For instance, one document shows the standard, nearly $2.9 million user fee payment to FDA from Pfizer. Other documents released include the fast track designation letter, which is not typically released, the confidential nonclinical overview for the vaccine, Pfizer’s request for a waiver from adding a suffix to the vaccine’s name (also not typically released), and another with a long list of anonymized trial subjects who didn’t receive the vaccine as randomized.

The sheer volume of pages and document types will give readers a good overall sense of the required documentation necessary to apply for a drug or vaccine approval at the FDA. But it’s still unclear if the documents will offer any new insight into the vaccine’s safety or efficacy, especially given the real-world data on the vaccine that’s already been published in major medical journals (e.g. Pfizer’s vaccine effectiveness and safety in health care personnel or Israel).

Anti-vax lawyer Aaron Siri, a managing partner of the firm Siri & Glimstad who represented the nonprofit, told Endpoints News, “Our job was to get the documents. We leave it to the scientists and others to analyze.”

Previously Siri wrote on his Substack that what drove this suit was that the government “wanted to hide the data by waiting to fully produce what it relied upon to license this product until almost every American alive today is dead.”

https://endpts.com/fda-begins-court-mandated-release-of-thousands-of-pages-on-pfizers-covid-19-vaccine-review/

Trucks, RVs and cars flock to Washington area to protest COVID restrictions

 

More than a thousand large trucks, recreational vehicles and cars are gathering on the outskirts of Washington as part of a protest against COVID-19 restrictions that threatens to roll on the U.S. capital in the coming days.

The so-called "People's Convoy," which originated in California and has drawn participants from around the country, is calling for an end to all pandemic-related restrictions. It was inspired by demonstrations last month that paralyzed Ottawa, Canada's capital city.

The convoy's message has been undercut in recent weeks as major U.S. cities have rolled back mask mandates and other measures against COVID-19, which has led to more than 950,000 deaths in the United States but has been mitigated with vaccines and therapeutics. President Joe Biden, a Democrat, signaled in his State of the Union speech on Tuesday that the country was entering a new, more controlled phase of the pandemic without business lockdowns or school closures.

Still, more than 100 18-wheeler trucks amassed with other vehicles on Friday evening at the Hagerstown Speedway, a racetrack about 80 miles (129 km) from downtown Washington, according to Reuters witnesses. Drivers continued to stream into the parking lot on Saturday morning, one witness said.

A website for the protest said they did not plan to enter "D.C. proper" and social media posts suggested they could remain at the racetrack on Saturday. But one participant who described himself as the lead trucker told a cheering crowd at the racetrack on Friday night that he would drive his truck into the heart of the American capital.

"D.C., the government, whomever, can claim that they have all this opposition for us waiting in D.C.," the man said. "But that flag on the back of my truck will go down to Constitution Avenue between the White House and the Washington Monument."

A little more than a year ago, supporters of former Republican President Donald Trump stormed the U.S. Capitol in an attack that left five people dead and more than 100 police officers injured.

U.S. federal law enforcement agencies have been coordinating with state and local authorities for weeks in preparation for the possible arrival of the convoy, said one U.S. official who requested anonymity to discuss internal operations.

A Feb. 26 U.S. Department of Homeland Security (DHS) bulletin to law enforcement reviewed by Reuters said trucker convoys could hinder emergency responders depending on the size of the protest.

The bulletin said federal law enforcement was not aware of any substantiated threats from domestic violent extremists, but that some extremists "probably will be drawn to the event and could engage in premeditated or opportunistic violence."

DHS said the possibility of an attack could be higher because COVID restrictions have been a "key driver" of domestic extremist violence over the last two years. Federal officials would be unlikely to see violent plotting in online public platforms beforehand due to the use of encrypted apps and private forums, it said.

Federal law enforcement is also cognizant of the need to respect the right to peaceful protest, the official said.

On Friday evening, a woman from nearby Silver Spring, Maryland, who identified herself only as "Dorothy" said she opposed COVID-related restrictions and that the issue had caused divisions in her family and problems at work.

"I think our medical choices are private and we should not be required to disclose them to participate in everyday activities," she told Reuters.

https://www.marketscreener.com/news/latest/Trucks-RVs-and-cars-flock-to-Washington-area-to-protest-COVID-restrictions--39678971/

Chinese City of Qingdao Reports Omicron Outbreak Among Students

 The Chinese port city of Qingdao reported 88 new coronavirus cases for March 5, all of them of the Omicron variant, fuelling China's highest number of daily locally transmitted cases so far this year.

China recorded 329 new coronavirus cases on the mainland on Saturday, 175 of them locally transmitted, the National Health Commission (NHC) said on Sunday, compared with 102 local cases a day earlier.

The Qingdao outbreak was mainly among middle school students in Laixi county, the Qingdao Municipal Health Commission said.

Laixi county will implement a second round of mass testing on March 7, a Qingdao official said at a news conference on Sunday, adding that there was no major risk of further outbreak.

China's "dynamic clearance" approach to COVID-19 aims shut off transmission routes as soon as new cases are detected.

The Qingdao outbreak helped send China's total local confirmed case count to its highest since Dec. 31, with other cases reported mainly in Jilin, Guangdong and Hebei provinces, according to the NHC.

The number of new asymptomatic cases, which China does not classify as confirmed cases, stood at 209, compared with 166 a day earlier.

As of March 5, mainland China had confirmed 110,868 COVID-19 cases and 4,636 fatalities.

https://www.usnews.com/news/world/articles/2022-03-05/chinese-city-of-qingdao-reports-omicron-outbreak-among-students

Roche starts new four-year trial of Alzheimer’s drug gantenerumab

 With prospects of an early, accelerated approval for Roche’s Alzheimer’s disease candidate gantenerumab looking diminished, the drugmaker has launched a new four-year trial in the hope of building its case for the drug.

The new placebo-controlled SKYLINE study will enrol 1,250 people aged 60 to 80 with the earliest biological signs of Alzheimer’s – in other words signs of amyloid accumulation in the central nervous system – but no cognitive impairment.

The aim is to see whether the anti-amyloid antibody can slow disease progression over a four-year follow-up period, which means the readout of the study will still be several years away.

Roche is collaborating on the study – billed as a “secondary prevention” trial – with the Banner Alzheimer’s Institute, Massachusetts General Hospital and the University of Southern California Alzheimer’s Therapeutic Research Institute.

There had been speculation last year that Roche would move ahead with a quick filing for gantenerumab after Biogen got a controversial accelerated approval for Aduhelm (aducanumab) using amyloid clearance as a surrogate endpoint, although that was downplayed by the company.

It has since indicated it will wait for the results of two pivotal trials in early (prodromal to mild) Alzheimer’s – GRADUATE 1 and 2 – that are due to read out in the fourth quarter of this year, before making a decision on filing.

Eli Lilly meanwhile has already started a rolling application for its amyloid drug donanemab based on phase 2 results, but pushed back its plans to complete the filing after a draft decision by Medicare to limit coverage of Aduhelm and other drugs in the class to approved clinical trials. It will now wait for the results of the phase 3 TRAILBALZER-ALZ 2 next year.

Biogen and Eisai have also kicked off a rolling application for their second amyloid antibody lecanemab – ahead of the results of clinical data from the pivotal CLARITY AD study, also due in the second half of this year – and Eisai said today it had gone down the same route in Japan.

The decision to launch another phase 3 trial shows that Roche is willing to play the long game, and gamble more money on gantenerumab in the hope that the role of anti-amyloid drugs will become clearer in the coming years.

The track record of the drug isn’t encouraging however, as gantenerumab has previously failed a phase 3 trial in Alzheimer’s patients with early signs of cognitive impairment in 2014, causing Roche to shelve the drug, only to resurrect it three years later.

In 2020, it also missed the mark in a study involving people with an early-onset, inherited form of Alzheimer’s disease.

One factor in gantenerumab’s favour is that it can be administered by subcutaneous injection rather than intravenous infusion, allowing to be administered by the patient at home every one or two weeks. For comparison, Aduhelm is dosed once a month at a clinic at least 21 days apart.

https://pharmaphorum.com/news/roche-starts-new-four-year-trial-of-alzheimers-drug-gantenerumab/

New research suggests a causal link between blood group and severe COVID-19

 A new study has analysed over 3000 proteins to identify which are causally linked to the development of severe COVID-19. This is the first study to assess such a large number of proteins for their connection to COVID-19. The findings provide insight into potential new targets for approaches to treat and prevent severe COVID-19.

Published in PLOS Genetics and part-funded by the National Institute for Health Research (NIHR) Maudsley Biomedical Research Centre, the study used a genetic tool to screen over 3000 proteins. Researchers identified six proteins that could underlie an increased risk of severe COVID-19 and eight that could contribute to protection from severe COVID-19.

One of the proteins (ABO) that was identified as having a causal connection to the risk of developing severe COVID-19 determines blood groups, suggesting that blood groups play an instrumental role in whether people develop severe forms of the disease.

Co-first author Dr Alish Palmos from Institute of Psychiatry, Psychology & Neuroscience (IoPPN) King’s College London said: “We have used a purely genetic approach to investigate a large number of blood proteins and established that a handful have causal links to the development of severe COVID-19. Honing in on this group of proteins is a vital first step in discovering potentially valuable targets for development of new treatments.”

Assessing how blood proteins are linked to disease can help understand the underlying mechanisms and identify potential new targets for developing or repurposing drugs. Protein levels can be measured directly from blood samples but conducting this type of research for large numbers of proteins is costly and cannot establish causal direction.

This is where genetics can play a role. Mendelian randomisation, a method of comparing causal relations between risk factors and health outcomes, using large genetic datasets can assess the relationship between genetic variants connected with an exposure (in this case high levels of individual blood proteins) and genetic variants connected with disease outcome (in this case severe COVID-19).  

Co-first author Dr Vincent Millischer from the Medical University of Vienna explained: “Causality between exposure and disease can be established because genetic variants inherited from parent to offspring are randomly assigned at conception similar to how a randomised controlled trial assigns people to groups. In our study the groups are defined by their genetic propensity to different blood protein levels, allowing an assessment of causal direction from high blood protein levels to COVID-19 severity whilst avoiding influence of environmental effects.”

The study considered two incremental levels of severity of COVID-19: hospitalisation and respiratory support or death. Using data from a number of genome-wide association studies the researchers found six proteins that were causally linked to an increased risk of hospitalisation or respiratory support/death due to COVID-19 and eight causally linked to protection against hospitalisation or respiratory support/death.

Analysis showed some distinction in types of proteins linked to hospitalisation and those linked to respiratory support/death, indicating different mechanisms may be at work in these two stages of disease. 

The analysis identified that an enzyme (ABO) that determines blood group was causally associated with both an increased risk of hospitalisation and a requirement for respiratory support. This supports previous findings around the association of blood group with higher likelihood of death. Taken together with previous research showing that the proportion of group A is higher in COVID-19 positive individuals, this suggests blood group A is candidate for follow-up studies.

Co-last author Dr Christopher Hübel from the IoPPN, King’s College London said: “The enzyme helps determine the blood group of an individual and our study has linked it with both risk of hospitalisation and the need of respiratory support or death. Our study does not link precise blood group with risk of severe COVID-19 but since previous research has found that proportion of people who are group A is higher in COVID-19 positive individuals, this suggests that blood group A is more likely candidate for follow-up studies.” 

Researchers also identified three adhesion molecules as being causally linked to a decreased risk of hospitalisation and requirement of respiratory support. As these adhesion molecules mediate interaction between immune cells and blood vessels this chimes with previous research suggesting that late stage COVID-19 is also a disease involving the linings of blood vessels. 

By identifying this suite of proteins, the research has highlighted a number possible targets for drugs that could be used to help treat severe COVID-19. These will need further clinical investigation which can be undertaken as part of the wider COVID-Clinical Neuroscience Study (COVID-CNS) which is investigating the causes behind different aspects of COVID-19.

Gerome Breen, Professor of Genetics at the IoPPN, and co-last author on the paper said: “What we have done in our study is provide a shortlist for the next stage of research. Out of 1000s of blood proteins we have whittled it down to about 14 that have some form of causal connection to the risk of severe COVID-19 and present a potentially important avenue for further research to better understand the mechanisms behind COVID-19 with an ultimate aim of developing new treatments but potentially also preventative therapies.”

The research was supported by NIHR Maudsley Biomedical Research Centre,  Medical Research Council, UK Research and Innovation, Wellcome Trust and the Lundbeck Foundation.

The paper ‘Proteome-wide Mendelian randomization identifies causal links between blood proteins and severe COVID-19’ was published in PLOS Genetics.

JOURNAL

PLoS Genetics

DOI

10.1371/journal.pgen.1010042 

METHOD OF RESEARCH

Observational study

SUBJECT OF RESEARCH

People

ARTICLE TITLE

Proteome-wide Mendelian randomization identifies causal links between blood proteins and severe COVID-19

ARTICLE PUBLICATION DATE

3-Mar-2022

https://www.eurekalert.org/news-releases/945181

'Urgent' COVID-19 funding hangs in balance amid partisan fight

 Funding for the next phase of the COVID-19 fight is hanging in the balance amid a showdown over new spending in Congress.  

The White House is calling for $22.5 billion for "immediate" needs ahead of next week's government funding deadline, but Republicans are resisting the request, saying the billions already provided to fight the virus should be spent first before Congress approves new money.  

The administration, though, says the previous money is “nearly all” used up. 

Without approval of the request for new funding, the White House says critical steps to fight the virus and prepare for a future variant will have to stop.  

“Let me be very clear: This is an urgent request,” White House Press Secretary Jen Psaki said Friday.   

Included in the request is $1.5 billion for next-generation “pan-COVID” vaccines that can work against multiple variants of the virus. Psaki also said testing capacity will drop “within weeks” if funding to sustain it is not provided, which would potentially require months of ramp-up if a new variant causes another surge.   

The administration also said funding is needed to purchase more antiviral pills, like the highly effective Pfizer treatment Paxlovid.  

Acting Office of Management and Budget Director Shalanda Young wrote in a letter to Congress that without quick action “available supply will decline as other countries place orders, creating a significant risk that the U.S. will be unable to secure the supply it needs.”  

“By September we anticipate our supply of oral antivirals will run out if additional pills are not purchased now,” Psaki said.

Asked on Thursday for a response on the White House’s argument that money is needed for pressing issues with the virus, Sen. Richard Shelby (Ala.), the top Republican on the Appropriations Committee, replied: “Let's spend the money we've already appropriated.”  

“There's billions of dollars out there that have been appropriated that haven't been spent, and I think they ought to spend that money first before they start asking us to borrow,” he later added.  

Doug Andres, a spokesman for Senate Minority Leader Mitch McConnell (R-Ky.) said there is over $100 billion in state and local funding from the American Rescue Plan remaining.   

Asked about state and local funding, an administration official said: “Congress designed these funds to be used over time, with a significant portion not available to us now.”  

“These funds will continue to be used as designed by Congress, and states and localities are anticipating and counting on these funds for important purposes, just like they’ve used the first tranche of funds,” the official added.   

Sen. Mitt Romney (R-Utah) led a letter with 35 other Senate Republicans asking the administration for an accounting of how COVID-19 money has already been spent before approving new money. A spokesperson for the Utah senator said Friday they had not received a formal response to the letter.  

The administration official said, “We’ve regularly briefed Congress on a bipartisan basis on the status of COVID relief funds.”  

A chart the administration previously sent to lawmakers and obtained by The Hill shows $0 in funding remaining unallocated across every category listed, from vaccines to treatments to the Strategic National Stockpile.   

Democratic congressional leaders say they are standing firm in pushing for new funds.   

“Some Republicans may think [money] should have been spent differently, but the point is that it has been spent,” said Senate Majority Leader Chuck Schumer (N.Y.). “We can’t pull those dollars back. And we need to provide new funding for possible variants.”  

“Either we act now to secure the progress we have made, or we risk backsliding if another contagious variant emerges in the fall and winter,” Schumer said.   

Speaker Nancy Pelosi (D-Calif.) added she hoped Republicans “would see the wisdom of the science of what we need to do in terms of COVID."  

Some advocates have been concerned that the administration did not make its formal request for COVID-19 funds sooner.   

The administration had previously informally briefed Congress on the need for $30 billion focused on the domestic response and $5 billion for global needs, but the formal request sent this week was somewhat smaller.   

Advocates have also criticized the $5 billion request for global needs, including vaccinating people in low-income countries, as far short of what is needed to help prevent new variants from forming around the globe.   

But even that $5 billion is not guaranteed amid the broader COVID-19 funding fight.   

An array of Democratic lawmakers, including Rep. Raja Krishnamoorthi (Ill.), Rep. Pramila Jayapal (Wash.) and Sen. Elizabeth Warren (Mass.) said in a joint statement on Thursday that the administration’s $5 billion request is “well below” what is needed, but urged its passage.   

“The global effort to vaccinate the world and end this pandemic is therefore fundamentally dependent on our colleagues in Congress, on both sides of the aisle, coming together to pass additional foreign aid funding,” they said.   

The White House also unveiled a lengthy plan for fighting the next phase of the virus this week, which won praise from many experts, but it requires new funding to be implemented.  

The White House said even the $22.5 billion request is not enough to fully fund the plan, and it anticipates asking for additional funding in the “weeks ahead.” Future COVID-19 requests are sure to face a tough hill to climb in Congress too, given the fight over the current spending.  

It remains to be seen if lawmakers can work out the current impasse.   

Asked Thursday if it was possible at least some new COVID-19 money could make it into the government funding package next week, Shelby replied: “It’s always possible.” 

https://thehill.com/policy/healthcare/596947-gop-resists-white-house-calls-for-urgent-covid-19-funding

Hochul’s Medicaid shake-up — if done right — could help both patients and taxpayers

 Gov. Kathy Hochul’s plan to boost competition for state Medicaid managed-care contracts could weed out some less-than-scrupulous operators and maybe save money down the road, but insurers are right to point out potential downsides.

Under the gov’s plan, the state would force Medicaid managed-care providers to compete for between two and five contracts per region. That could give regulators a chance to better vet players, improve services and rates and shut out those who try to game the system (say, by recruiting patients who don’t really need Medicaid services). Legitimate patients might wind up better off. Taxpayers, too.

Yet managed-care providers rightly note that the competition process itself will be expensive, time-consuming and potentially chaotic — for them, the state, health-care providers and patients. Indeed, some Medicaid recipients would be forced to switch plans, if theirs isn’t offered.

“This has the potential to be extremely disruptive,” warns New York Health Plan Association President Eric Linzer.

Limiting the number of managed-care providers to just five, at most, could also invite pay-for-play corruption, though that’s a danger with any contracting.

If Hochul’s plan (now part of her budget proposal) becomes law, the state will need to handle the transition carefully: Do whatever’s necessary to limit the chaos and expense (for insurers and state bureaucrats) of the bidding process. Guard against corruption by making the process fully transparent, with pre-established criteria for choosing winners.

And why on Earth does Hochul suggest considering whether plan providers are for-profit companies? If they offer the best product at the lowest cost, who cares if they make a profit?

All this, of course, amounts to a modest reform of a Medicaid program that costs more than $80 billion a year and, though meant for the poor, covers nearly 40% of the state’s population. But small steps for small feet.

Let’s just hope any improvements the state makes to this part of the program more than offset any damage it causes.

https://nypost.com/2022/03/05/hochuls-medicaid-shake-up-could-help-both-patients-and-taxpayers/