No reference for the source of this picture.

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• Losartan is not a receptor, but it does block a chemical (angiotensin II), from binding to a receptor, type 1 angiotensin 2 (AT1), which lowers blood pressure.
• Losartan does not block the virus causing COVID-19, called SARS-CoV-2, but it may reduce the activity of the renin-angiotensin system, which is overactive in people with high blood pressure, which may increase their risk of developing lung complications from COVID-19.
• Some animal studies found losartan beneficial at reducing severe simulated lung injury in mice exposed to other viruses, such as SARS. Few human studies have been conducted.
• For now, any beneficial effects of losartan are just a hypothesis (suggestion). It is not a good idea to institute any medical therapy based on an untested hypothesis since unexpected harms may outweigh any benefits.
• For people already taking losartan or any other ARB, the advice from the medical community is to keep taking it unless your doctor tells you otherwise.

Losartan (Cozaar) belongs to a class of medicines called Angiotensin Receptor Blockers (ARBs), also known as Angiotensin II receptor antagonists.

Losartan work by blocking the action of a natural chemical called angiotensin II. ARBs prevent angiotensin II from binding to type 1 angiotensin 2 receptors (AT1) located in the heart, blood vessels, kidney, adrenal cortex, lung, and brain. Losartan, therefore, works on the renin-angiotensin system (RAS) which is a hormonal system that regulates blood pressure.

Losartan is not a receptor, but it does block a chemical (angiotensin II) from binding to a receptor (AT1), which lowers blood pressure.

Losartan has attracted interest from the medical community because losartan was used in some preclinical studies to determine its effectiveness against the SARS virus that first appeared in 2002. SARS was also a coronavirus and is like SARS-CoV-2, the virus that causes COVID-19.

The research was based on the theory that inhibition of an overactive RAS might increase the risk of pulmonary complications from viral infections. Studies that were conducted include:

• Mice treated with losartan after an acid-induced lung injury and exposed to the SARS virus had less lung injury and fluid around their lungs than mice treated with placebo
• Losartan, in addition to infusions of angiotensin-2, prevented severe lung injury and edema in mice that had had all their ACE-2 removed
• Recombinant ACE2 infusions have improved lung injury in people with SARS
• Acute respiratory distress syndrome secondary to reduced ACE2 activity has been observed in other viral pneumonias, such as H5N1 and H7N9 influenza
• Mice given losartan after infection with H5N1 influenza had reduced lung edema and an increased rate of survival

We do not know whether the supposed benefits of ARBs during an episode of infection with SARS-CoV-2 outweigh the potential harms.

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Published: Dec. 16, 2020 at 11:04 a.m. ET

By Jaimy Lee

Wall Street analysts expect that the week will end with the FDA granting an emergency use authorization to the company’s experimental vaccine. 

If the Food and Drug Administration authorizes Moderna Inc.’s COVID-19 vaccine candidate, it will be the second vaccine to be made available to Americans during the coronavirus pandemic — and the first-ever authorized product for the 10-year-old biotech.

Shares of Moderna MRNA, +1.65% were down 6.7% in trading on Wednesday morning, though Wall Street analysts largely expect that the week will end with the FDA granting an emergency use authorization to the company’s experimental COVID-19 vaccine.

The regulator on Tuesday called mRNA-1273 “highly effective” in a report published in advance of a FDA advisory committee meeting scheduled for Thursday that will allow a group of independent medical experts to discuss the risks and benefits of the still investigational vaccine. This is the final regulatory step before the FDA decides whether to authorize the vaccine.

Moderna has said its coronavirus vaccine candidate has an efficacy rate of about 94%, based on data from clinical trials.

Unlike Pfizer Inc. PFE, +1.00%, a traditional pharmaceutical company with a wide-ranging portfolio of commercialized medicines that last week received emergency authorization from the FDA for the COVID-19 vaccine it developed with German biotech BioNTech BNTX, +9.35%, Moderna has never had one of its products make it as far along in the regulatory process as mRNA-1273.

The company, which has no FDA-approved or authorized products, has seen its market capitalization increase to about $54.3 billion in recent trading from just $6.6 billion at the end of 2019, according to FactSet data. In comparison, Pfizer’s market cap was $211.1 billion.

Moderna’s stock tumbled to a low for the year at $17.78 on Jan. 7, five days before it announced plans to begin developing a vaccine aimed at preventing infection with what was then referred to as the novel coronavirus. At that time, the virus was still primarily infecting people in Wuhan, China.

Since then, Moderna’s stock had soared, closing at an all-time high of $169.86 on Dec. 8.

In the last 11 months, the vaccine has moved through the three phases of clinical trials, and Moderna has announced multiple deals with governments around the world to acquires doses of its vaccine candidate. This includes about $1 billion to support clinical trials and manufacturing build-out from the National Institutes of Health and the planned purchase of 200 million doses from the U.S. government.

“What has limited us in the past was capital,” Moderna CEO Stéphane Bancel said this month at an investor conference, according to a FactSet transcript of the call. “You could see us sitting on a very substantial balance sheet at the end of 2021, which I think will be an equitable stepping stone for us to scale Moderna.”

The rapid rise in Moderna’s value prompted Morgan Stanley analyst Matthew Harrison to downgrade the company on Wednesday to equal weight from overweight. Although Harrison sees “significant” potential for Moderna over the long term, any near-term COVID-19 value has already been largely priced into the stock.

The focus of the company’s research and development pipeline is the same mRNA, or messenger ribonucleuc acid, technology it is using for the COVID-19 vaccine. It’s been testing mRNA vaccines for cancers like melanoma and solid tumors, other infectious diseases like Zika, and some rare, inherited disorders like methylmalonic acidemia. None of the experimental vaccines have made it through mid-stage clinical trials except for its COVID-19 vaccine.

The FDA last week authorized the BioNTech/Pfizer vaccine one day after the advisory committee voted 17-4-1 that the benefits of their vaccine outweigh the risks. (The FDA isn’t required to follow the advice of the committee but often does.) The “no” votes from four of the independent medical experts on the committee were attributed to concern about allowing the vaccine to be administered to teens who are at least 16 years old.

The authorization made the BioNTech/Pfizer vaccine the first to be authorized in the U.S. and also marked the first time that regulatory approval of any kind was granted to a mRNA product.

Because Moderna is seeking authorization for people who are at least 18 years old, some analysts expect a unanimous vote in favor of the FDA authorizing mRNA-1273. “This should not be an issue for Moderna given the trial and EUA request,” Raymond James analyst Steven Seedhouse told investors on Wednesday.

Moderna’s stock has rallied 602.0% so far this year. The S&P 500 SPX, +0.74% has gained 14.5% since the start of the year.

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US-based pharmaceutical giant Pfizer has made the first compensation payment to Nigerian families affected by a controversial drug trial 15 years ago.

It paid $175,000 (£108,000) each to four families in the first of a series of payments it is expected to make.

The payouts are part of an out-of-court settlement reached in 2009.

In 1996, 11 children died and dozens were left disabled after Pfizer gave them the experimental anti-meningitis drug, Trovan.

The payouts were made to the parents of four of the children who died.

Their parents told the BBC they welcomed the payment, but it would not replace the loss of their loved ones.

The children were part of a group of 200 given the drug during a meningitis epidemic in the northern city of Kano as part of a medical trial comparing Trovan’s effectiveness with the established treatment.

For years Pfizer maintained that meningitis – not the drug – caused the deaths and disabilities.

But after a lengthy and expensive litigation process, it reached a settlement with the Kano government in northern Nigeria.

DNA tests

The trials were carried out in Kano and the state government fought Pfizer on behalf of victims and their families.

It has taken two years and DNA tests to establish who is entitled to payments, the BBC’s Jonah Fisher in Lagos says.

It could take another year for payments to be concluded, he says.

Pfizer also agreed to sponsor health projects in Kano as well as creating a fund of $35m to compensate those affected.

Pfizer said it was pleased the four had been compensated.

“This is the first step in a multi-phase review process by which the independent board of trustees that manages the fund will deliver payment to all other qualified claimants,” the company said in a statement.

“We thank them for their commitment and dedication to seeing this process through in the most timely and transparent way possible.”

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Pharmaceutical company Pfizer, Inc. (Pfizer), based in New York, NY, has agreed to pay $23.85 million to resolve claims that it used a foundation as a conduit to pay the copays of Medicare patients taking three Pfizer drugs, in violation of the False Claims Act, the Justice Department announced today.  

When a Medicare beneficiary obtains a prescription drug covered by Medicare Part B or Part D, the beneficiary may be required to make a partial payment, which may take the form of a copayment, coinsurance, or deductible (collectively copays).  Congress included copay requirements in the Medicare program, in part, to encourage market forces to serve as a check on health care costs, including the prices that pharmaceutical manufacturers can demand for their drugs.  Under the Anti-Kickback Statute, a pharmaceutical company is prohibited from offering, directly or indirectly, any remuneration—which includes paying patients’ copay obligations—to induce Medicare patients to purchase the company’s drugs. 

As part of today’s settlement, the government alleged that Pfizer used a foundation as a conduit to pay the copay obligations of Medicare patients taking three Pfizer drugs:  Sutent and Inlyta, which both treat renal cell carcinoma, and Tikosyn, which treats arrhythmia in patients with atrial fibrillation or atrial flutter.  The government alleged that, in order to generate revenue, and instead of giving Sutent and Inlyta to Medicare patients who met the financial qualifications of Pfizer’s existing free drug program, Pfizer used a third-party specialty pharmacy to transition certain patients to the foundation, which covered the patients’ Medicare copays.  Pfizer allegedly made donations to the foundation to enable it to cover the copays of these patients and received confirmation from the foundation, via the specialty pharmacy, that the foundation funded the copays.  

With respect to Tikosyn, Pfizer raised the wholesale acquisition cost of a package of forty .125 mg capsules of the drug by over 40 percent in the last three months of 2015.  Pfizer allegedly knew that the price increase would also increase Medicare beneficiaries’ copay obligations for Tikosyn, and potentially prevent some patients from being able to afford the drug.  Pfizer allegedly worked with the foundation to create and finance a fund for Medicare patients suffering from the condition treated by Tikosyn, coordinated the opening of the fund with the implementation of its price increase for the drug, and referred patients to the fund.  For the next nine months, Tikosyn patients accounted for virtually all of the beneficiaries whose copayments were paid by the fund.

“Kickbacks undermine the independence of physician and patient decision-making, and raise healthcare costs,” said Acting Assistant Attorney General Chad A. Readler of the Justice Department’s Civil Division.  “As today’s settlement makes clear, the Department will hold accountable drug companies that pay illegal kickbacks—whether directly or indirectly—to undermine taxpayer funded healthcare programs, including Medicare.”

“Pfizer used a third party to saddle Medicare with extra costs,” said United States Attorney Andrew E. Lelling.  “According to the allegations in today’s settlement agreement, Pfizer knew that the third-party foundation was using Pfizer’s money to cover the co-pays of patients taking Pfizer drugs, thus generating more revenue for Pfizer and masking the effect of Pfizer’s price increases.  The Anti-Kickback Statute exists to protect Medicare, and the taxpayers who fund it, from schemes like these.  At the same time, we commend Pfizer for stepping forward to resolve these issues in a responsible manner.”  

“Today’s settlement demonstrates the FBI’s commitment to making sure patients receive, and the government pays for, health care that is not compromised by kickbacks,” said Harold H. Shaw, Special Agent in Charge, FBI Boston Division.  “What Pfizer is accused of doing in this case—masking charitable contributions to increase company profits—violates the basic trust patients extend to the healthcare system and threatens the financial integrity of the Medicare program.”

Pfizer has also entered into a corporate integrity agreement (CIA) with the Department of Health and Human Services Office of Inspector General (HHS-OIG).  The five-year CIA requires, among other things, that Pfizer implement measures designed to ensure that arrangements and interactions with third-party patient assistance programs are compliant with the law.  In addition, the CIA requires reviews by an independent review organization, compliance-related certifications from company executives and Board members, and the implementation of a risk assessment and mitigation process.

“Our corporate integrity agreement promotes independence between Pfizer and any patient assistance programs to which it may donate,” said Gregory E. Demske, Chief Counsel to the Inspector General for the United States Department of Health and human Services.  “Without true independence, as we have seen in this case, drug companies may use patient assistance programs as conduits for improper payments that harm Medicare.”

The government’s resolution of this matter illustrates the government’s emphasis on combating healthcare fraud.  One of the most powerful tools in this effort is the False Claims Act.  Tips and complaints from all sources about potential fraud, waste, abuse, and mismanagement, can be reported to the Department of Health and Human Services at 800-HHS-TIPS (800-447-8477).

The investigation was conducted by the Justice Department’s Civil Division and the U.S. Attorney’s Office for the District of Massachusetts, in conjunction with the Department of Health and Human Services, Office of Inspector General; the Federal Bureau of Investigation: the Department of Veterans Affairs, Office of Inspector General; and the United States Postal Inspection Service.  

The claims resolved by the settlement are allegations only; there has been no determination of liability. 

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Pfizer to Pay $2.3 Billion for Fraudulent Marketing

WASHINGTON – American pharmaceutical giant Pfizer Inc. and its subsidiary Pharmacia & Upjohn Company Inc. (hereinafter together “Pfizer”) have agreed to pay $2.3 billion, the largest health care fraud settlement in the history of the Department of Justice, to resolve criminal and civil liability arising from the illegal promotion of certain pharmaceutical products, the Justice Department announced today.

Pharmacia & Upjohn Company has agreed to plead guilty to a felony violation of the Food, Drug and Cosmetic Act for misbranding Bextra with the intent to defraud or mislead. Bextra is an anti-inflammatory drug that Pfizer pulled from the market in 2005. Under the provisions of the Food, Drug and Cosmetic Act, a company must specify the intended uses of a product in its new drug application to FDA. Once approved, the drug may not be marketed or promoted for so-called “off-label” uses – i.e., any use not specified in an application and approved by FDA. Pfizer promoted the sale of Bextra for several uses and dosages that the FDA specifically declined to approve due to safety concerns. The company will pay a criminal fine of $1.195 billion, the largest criminal fine ever imposed in the United States for any matter. Pharmacia & Upjohn will also forfeit $105 million, for a total criminal resolution of $1.3 billion.

In addition, Pfizer has agreed to pay $1 billion to resolve allegations under the civil False Claims Act that the company illegally promoted four drugs – Bextra; Geodon, an anti-psychotic drug; Zyvox, an antibiotic; and Lyrica, an anti-epileptic drug – and caused false claims to be submitted to government health care programs for uses that were not medically accepted indications and therefore not covered by those programs. The civil settlement also resolves allegations that Pfizer paid kickbacks to health care providers to induce them to prescribe these, as well as other, drugs. The federal share of the civil settlement is $668,514,830 and the state Medicaid share of the civil settlement is $331,485,170. This is the largest civil fraud settlement in history against a pharmaceutical company.

As part of the settlement, Pfizer also has agreed to enter into an expansive corporate integrity agreement with the Office of Inspector General of the Department of Health and Human Services. That agreement provides for procedures and reviews to be put in place to avoid and promptly detect conduct similar to that which gave rise to this matter.

Whistleblower lawsuits filed under the qui tam provisions of the False Claims Act that are pending in the District of Massachusetts, the Eastern District of Pennsylvania and the Eastern District of Kentucky triggered this investigation. As a part of today’s resolution, six whistleblowers will receive payments totaling more than $102 million from the federal share of the civil recovery.

The U.S. Attorney’s offices for the District of Massachusetts, the Eastern District of Pennsylvania, and the Eastern District of Kentucky, and the Civil Division of the Department of Justice handled these cases. The U.S. Attorney’s Office for the District of Massachusetts led the criminal investigation of Bextra. The investigation was conducted by the Office of Inspector General for the Department of Health and Human Services (HHS), the FBI, the Defense Criminal Investigative Service (DCIS), the Office of Criminal Investigations for the Food and Drug Administration (FDA), the Veterans’ Administration’s (VA) Office of Criminal Investigations, the Office of the Inspector General for the Office of Personnel Management (OPM), the Office of the Inspector General for the United States Postal Service (USPS), the National Association of Medicaid Fraud Control Units and the offices of various state Attorneys General.

“Today’s landmark settlement is an example of the Department of Justice’s ongoing and intensive efforts to protect the American public and recover funds for the federal treasury and the public from those who seek to earn a profit through fraud. It shows one of the many ways in which federal government, in partnership with its state and local allies, can help the American people at a time when budgets are tight and health care costs are increasing,” said Associate Attorney General Tom Perrelli. “This settlement is a testament to the type of broad, coordinated effort among federal agencies and with our state and local partners that is at the core of the Department of Justice’s approach to law enforcement.”

“This historic settlement will return nearly $1 billion to Medicare, Medicaid, and other government insurance programs, securing their future for the Americans who depend on these programs,”said Kathleen Sebelius, Secretary of Department of Health and Human Services”The Department of Health and Human Services will continue to seek opportunities to work with its government partners to prosecute fraud wherever we can find it. But we will also look for new ways to prevent fraud before it happens. Health care is too important to let a single dollar go to waste.”

“Illegal conduct and fraud by pharmaceutical companies puts the public health at risk, corrupts medical decisions by health care providers, and costs the government billions of dollars,” said Tony West, Assistant Attorney General for the Civil Division. “This civil settlement and plea agreement by Pfizer represent yet another example of what penalties will be faced when a pharmaceutical company puts profits ahead of patient welfare.”

“The size and seriousness of this resolution, including the huge criminal fine of $1.3 billion, reflect the seriousness and scope of Pfizer’s crimes,” said Mike Loucks, acting U.S. Attorney for the District of Massachusetts. “Pfizer violated the law over an extensive time period. Furthermore, at the very same time Pfizer was in our office negotiating and resolving the allegations of criminal conduct by its then newly acquired subsidiary, Warner-Lambert, Pfizer was itself in its other operations violating those very same laws. Today’s enormous fine demonstrates that such blatant and continued disregard of the law will not be tolerated.”

“Although these types of investigations are often long and complicated and require many resources to achieve positive results, the FBI will not be deterred from continuing to ensure that pharmaceutical companies conduct business in a lawful manner,” said Kevin Perkins, FBI Assistant Director, Criminal Investigative Division.

“This resolution protects the FDA in its vital mission of ensuring that drugs are safe and effective. When manufacturers undermine the FDA’s rules, they interfere with a doctor’s judgment and can put patient health at risk,” commented Michael L. Levy, U.S. Attorney for the Eastern District of Pennsylvania. “The public trusts companies to market their drugs for uses that FDA has approved, and trusts that doctors are using independent judgment. Federal health dollars should only be spent on treatment decisions untainted by misinformation from manufacturers concerned with the bottom line.”

“This settlement demonstrates the ongoing efforts to pursue violations of the False Claims Act and recover taxpayer dollars for the Medicare and Medicaid programs,” noted Jim Zerhusen, U.S. Attorney for the Eastern District of Kentucky.

“This historic settlement emphasizes the government’s commitment to corporate and individual accountability and to transparency throughout the pharmaceutical industry,” said Daniel R. Levinson, Inspector General of the United States Department of Health and Human Services. “The corporate integrity agreement requires senior Pfizer executives and board members to complete annual compliance certifications and opens Pfizer to more public scrutiny by requiring it to make detailed disclosures on its Web site. We expect this agreement to increase integrity in the marketing of pharmaceuticals.”

“The off-label promotion of pharmaceutical drugs by Pfizer significantly impacted the integrity of TRICARE, the Department of Defense’s healthcare system,” said Sharon Woods, Director, Defense Criminal Investigative Service. “This illegal activity increases patients’ costs, threatens their safety and negatively affects the delivery of healthcare services to the over nine million military members, retirees and their families who rely on this system. Today’s charges and settlement demonstrate the ongoing commitment of the Defense Criminal Investigative Service and its law enforcement partners to investigate and prosecute those that abuse the government’s healthcare programs at the expense of the taxpayers and patients.”

“Federal employees deserve health care providers and suppliers, including drug manufacturers, that meet the highest standards of ethical and professional behavior,” said Patrick E. McFarland, Inspector General of the U.S. Office of Personnel Management. “Today’s settlement reminds the pharmaceutical industry that it must observe those standards and reflects the commitment of federal law enforcement organizations to pursue improper and illegal conduct that places health care consumers at risk.”

“Health care fraud has a significant financial impact on the Postal Service. This case alone impacted more than 10,000 postal employees on workers’ compensation who were treated with these drugs,” said Joseph Finn, Special Agent in Charge for the Postal Service’s Office of Inspector General. “Last year the Postal Service paid more than $1 billion in workers’ compensation benefits to postal employees injured on the job.”

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None of the potentially contaminated Johnson & Johnson shots produced at the Baltimore Emergency BioSolutions were ever distributed, but 15 million doses had to be discarded. The latest report says more may be compromised.

CBS News: FDA Inspectors Find “Brown Residue” And Other Violations In Plant Making Johnson & Johnson Vaccine The Baltimore factory contracted to make Johnson & Johnson’s COVID-19 vaccine was dirty, didn’t follow proper manufacturing procedures and had poorly trained staff, resulting in contamination of material that was going to be put in the shots, U.S. regulators said Wednesday. The Food and Drug Administration released a statement and a 13-page report detailing findings from its recent inspection of the now-idle Emergent BioSciences factory. Agency inspectors said a batch of bulk drug substance for J&J’s single-shot vaccine was contaminated with material used to make COVID-19 vaccines for another Emergent client, AstraZeneca. That batch, reportedly enough to make about 15 million J&J vaccine doses, had to be thrown out. (4/21)

NPR: FDA Inspection Finds Numerous Problems At Facility Intended To Make J&J VaccinePeeling paint. Cracked buckets. Employees dragging unsealed bags of medical waste. Procedures ignored. Inadequately trained staff. All of these were problems noted by U.S. Food and Drug Administration inspectors at the Emergent BioSolutions factory in Baltimore – a facility that is intended to produce materials for the Johnson & Johnson COVID-19 vaccine. That plan is on hold, following a problem last month with a batch of a vaccine ingredient there, and now a range of documented issues at the facility. (Wamsley, 4/21)

The New York Times: Federal Inspectors Fear More Vaccines Were Exposed To Contamination“There is no assurance that other batches have not been subject to cross-contamination,” the F.D.A.’s 12-page report states. The report amounted to a harsh rebuke of Emergent, which had long played down setbacks at the factory, and added to problems for Johnson & Johnson, whose vaccine had been seen as a game changer because it requires only one shot, can be produced in mass volume and is easily stored. (LaFraniere, Stolberg and Hamby, 4/21)

Politico: FDA Inspection Report Casts Doubt On J&J Vaccine Contractor’s Ability To Restart Production Emergent said that it is working with FDA and J&J to resolve the issues quickly. “While we are never satisfied to see shortcomings in our manufacturing facilities or process, they are correctable and we will take swift action to remedy them,” the company said in a statement. It added that “the issuance of findings by the FDA is normal following a facility inspection and provides direction on the necessary steps to improve operations.” But it is rare for the agency to move so quickly —releasing a report on an inspection concluded just a day earlier — and to accompany its findings with a statement by top FDA officials. (Owermohle and Banco, 4/21)This is part of the KHN Morning Briefing, a summary of health policy coverage from major news organizations. Sign up for an email subscription.

https://youtu.be/BHk1L3-1YiE

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The document linked above from the CDC raises the bar by which the RT-PCR test will find a positive result in vaccinated individuals.

A RT-PCR Ct Value much lower than what was used to identify a non vaccinated “case” in 2020 does not offer an apples to apples comparison to 2021. RT-PCR Ct Value was lowered relative to 2020 starting around January 7th, 2021 (from 42 to 35) and now this is evidence of an even higher bar to be considered a positive case (less than or equal to 28) once vaccinated.

Making it more difficult to achieve a positive case means less cases. If you apply the same RT-PCR Ct value to 2020, the case numbers would decrease.

COVID-19 vaccine breakthrough case investigation

Information for public health, clinical, and reference laboratories

“Case definition 

A person who has SARS-CoV-2 RNA or antigen detected on respiratory specimen collected ≥14 days after completing the primary series of an FDA-authorized COVID-19 vaccine. “

…

“Clinical specimens for sequencing should have an RT-PCR Ct value ≤28.“