Pharmacy chains face first trial in U.S. opioid litigation, judge urges settlement

 Four large pharmacy chains are set to face their first trial over the deadly U.S. opioid epidemic, creating new pressure to reach settlements with state and local governments who accuse them of contributing to the public health crisis.

The Ohio counties of Lake and Trumbull allege that oversight failures at pharmacies run by Walgreens Boots Alliance Inc (WBA.O), CVS Health Corp (CVS.N), Walmart Inc (WMT.N) and Giant Eagle Inc (GIAEG.UL) led to excessive amounts of opioid pills in their communities.

Lawyers for the counties and companies are set to deliver opening statements on Monday to a federal jury in Cleveland, where thousands of similar lawsuits against pharmaceutical companies, drug distributors and pharmacies are pending.

More than 3,300 cases have been brought largely by state and local governments seeking to hold the companies responsible for an opioid abuse epidemic that U.S. government data shows led to nearly 500,000 overdose deaths from 1999 to 2019.

Should a jury find the companies liable, U.S. District Judge Dan Polster will later determine how much they must pay to abate, or address, the epidemic in the communities.

Lawyers for the local governments have said the pharmacy chains are among their next targets for settlement.

Polster, who oversees most of the opioid lawsuits, on Tuesday renewed his long-running push for a global settlement by the companies. "Use this trial as an opportunity to engage in the kind of meaningful discussions that have not happened over the last couple of years, all right?" he said.

At trial, the two counties are expected to argue the pharmacies created a public nuisance by failing to identify red flags and ensure prescriptions were valid, causing an oversupply of pills, overdoses and deaths.

"The national chain pharmacies in our case refused to give their pharmacists the necessary tools and opportunities to follow the law and stop the diversion and improper sale of opiates," said Mark Lanier, the counties' lawyer.

The companies deny wrongdoing, saying criminals were more likely to obtain opioids illegally from other sources, including pill mills, crooked doctors and drug traffickers.

"Opioid prescriptions are written by doctors, not pharmacists," CVS said in a statement. "Our pharmacies fill legitimate prescriptions written by licensed doctors."

Giant Eagle said Ohio regulators inspected its pharmacies in the two counties nearly 100 times during the relevant time period and concluded it complied with the law. The other defendants did not respond to requests for comment.

The trial comes after the three largest U.S. distributors that supply pharmacies - McKesson Corp (MCK.N), Cardinal Health Inc (CAH.N) and AmerisourceBergen Corp (ABC.N) - and the drugmaker Johnson & Johnson (JNJ.N) in July proposed paying up to $26 billion to settle cases against them. read more

A bankruptcy judge in August approved a settlement by OxyContin maker Purdue Pharma LP and its wealthy Sackler family owners that the company values at more than $10 billion. read more

The pharmacy chains in the Ohio case have only settled one case nationally. Ahead of a trial in New York, they and Rite Aid Corp (RAD.N) agreed pay $26 million to settle with two counties.

Rite Aid settled pre-trial in Ohio and agreed to pay Trumbull at least $1.5 million. Lake County has not disclosed its recovery.

https://www.reuters.com/world/us/pharmacy-chains-face-first-trial-us-opioid-litigation-judge-urges-settlement-2021-10-01/

U.S. Judge upholds COVID-19 vaccine requirement for those with 'natural immunity'

 A U.S. judge upheld the University of California's COVID-19 vaccine requirement against a challenge by a professor who alleged he had immunity due to a prior coronavirus infection, in what appears to be the first ruling on the issue.

U.S. District Court Judge James Selna in Santa Ana, California, said the university system acted rationally to protect public health by mandating the vaccine and not exempting individuals with some level of immunity from an infection.

More than 43 million Americans have had confirmed cases of COVID-19 and some opponents of vaccinations have argued that immunity from an infection negates the need for an inoculation.

The U.S. Centers for Disease Control and Prevention (CDC) said on Aug. 6 that a study showed vaccines offer better protection than natural immunity gained from prior infection, which wanes over time.

On Wednesday, a group of physicians who are Republican members of Congress wrote to the CDC to urge the agency to acknowledge natural immunity.

The lawmakers said if the growing number of vaccine mandates ignore natural immunity it could lead to labor shortages as people are fired for failing to get a shot. Their letter said such mandates could even trigger a security crisis because up to 20% of the military faces "separation" and many of them "likely have natural immunity."

Selna's ruling denied a motion for a preliminary injunction by Aaron Kheriaty. And while Selna said the professor at the University of California, Irvine School of Medicine did not show a likelihood of success, Kheriaty said he plans to continue the litigation.

He told Reuters he plans to use the discovery process to determine how the policy was formulated and to question the university's expert witnesses about their reasoning for rejecting his arguments on natural immunity.

https://www.reuters.com/world/us/us-judge-upholds-covid-19-vaccine-requirement-those-with-natural-immunity-2021-09-30/

BioNTech: 1st Patient Dosed in Phase 2 Trial of mRNA Colorectal Cancer Immunotherapy

 Second Phase 2 trial initiated from BioNTech's proprietary individualized

      mRNA-based cancer vaccine platform iNeST 
 
   -- Randomized Phase 2 trial will enroll approximately 200 patients with 
      high-risk colorectal cancer that are circulating tumor DNA positive after 
      adjuvant treatment 
 
   -- BioNTech-sponsored trial is initiated in the United States, Germany, 
      Spain and Belgium and is enrolling patients immediately 
 
   -- BioNTech will continue joint development of BNT122 (autogene cevumeran, 
      RO7198457) with Genentech, a member of the Roche Group, in other trials 

BioNTech SE (NASDAQ: BNTX, "BioNTech" or "the Company"), announced today that the first colorectal cancer patient has been treated with its individualized mRNA cancer vaccine BNT122 (autogene cevumeran, RO7198457) in a Phase 2 clinical trial. The trial has been initiated in the United States, Germany, Spain and Belgium. It is planned to enroll about 200 patients to evaluate the efficacy of RO7198457 (BNT122) compared to watchful waiting after surgery and chemotherapy, the current standard of care for these high-risk patients. As the second deadliest cancer worldwide, the medical need for novel therapies to treat colorectal cancer remains high.

https://www.marketscreener.com/quote/stock/BIONTECH-SE-66771992/news/Press-Release-BioNTech-Expands-Clinical-Oncology-Portfolio-with-First-Patient-Dosed-in-Phase-2-Tri-36566210/

AstraZeneca COVID-19 Jab Shows 74% Efficacy In US Trial

 

• Reuters reported that large U.S. trial results of AstraZeneca Plc's 
  AZN +0.65%
   (Get Free Alerts for AZN) COVID-19 vaccine demonstrated 74% efficacy at preventing symptomatic disease.
• In people aged 65 and older, the efficacy increased to 83.5%
• Overall efficacy of 74% was lower than the interim 79% reported in March, a result AstraZeneca revised days later to 76% after a rare public rebuke from health officials that the figure was based on "outdated information."
• The study included data from more than 26,000 volunteers in the United States, Chile, and Peru.
• There were no cases of severe or critical symptomatic COVID-19 among the more than 17,600 participants who got the vaccine, compared with 8 cases among the 8,500 volunteers on placebo. 
• There were also two deaths in the placebo group but none among those who received the vaccine.
• "I was pleasantly surprised," Dr. Anna Durbin, a vaccine researcher at Johns Hopkins University and one of the study's investigators, said of the overall result. "It was also highly protective against severe disease and hospitalization," she said.
• No blood clotting side effects linked to the vaccine were observed during the study.
• AstraZeneca said it plans to file for full approval with the FDA rather than seek emergency use authorization. 

https://www.benzinga.com/general/biotech/21/09/23179216/astrazeneca-covid-19-jab-shows-74-efficacy-in-us-trial

How nanomaterial aids antibody response

 

Illustration shows how a nanomaterial links with receptors on the immune system's B cells and helps them initiate antibody production. The top two panels show anti-immunoglobulin antibody fragments (brown) binding to immune system B cell receptors (blue). Micelles (spheres) don't interact with B cell receptors without these fragments (bottom left panel). In the presence of the fragments, the micelles link the fragments and B cell receptors (bottom right panel), boosting antibody production. Credit: Nanovaccine Institute

The researchers' original task was to figure out how certain polymer nanomaterials provided for a low-inflammatory immune response and yet were able to boost antibody production as part of a single dose of vaccine.

Once they learned how these nanomaterials just 20 to 30 billionths of a meter in size acted as vaccine-aiding adjuvants, they decided to take the next scientific step.

Could these same tiny adjuvants carry real-world antigens to the immune system's B cells and turn them into antibody-secreting factories? In addition, could this be an alternative way to produce laboratory antibodies for diagnostic and therapeutic applications?

The answers were yes. Cell-culture experiments with the technique produced antibodies against key antigens from the coronavirus that causes COVID-19 and the bacterium that causes pneumonic plague.

The initial observation and subsequent discovery show how researchers affiliated with the Nanovaccine Institute based at Iowa State University look at their research from many perspectives:

"This is a great example of the healthy tug of war between a basic research finding about the mechanism of antibody production and a translational benefit that we may have invented a new antibody-production platform," said Balaji Narasimhan, the director of the Nanovaccine Institute, an Iowa State Anson Marston Distinguished Professor in Engineering and the Vlasta Klima Balloun Faculty Chair. "The Nanovaccine Institute is burning both sides of that candle."

The journal Science Advances recently published the researchers' findings. First author is Sujata Senapati, a former Iowa State doctoral student in chemical and biological engineering. Corresponding authors are Narasimhan and Surya Mallapragada, an Iowa State Anson Marston Distinguished Professor in Engineering, an associate vice president for research and the Carol Vohs Johnson Chair in Chemical and Biological Engineering. (See sidebar for the full research team.)

Grants from the National Institute of Allergy and Infectious Diseases, a part of the National Institutes of Health, supported the researchers' work.

It's like a ladder

It was clear to the researchers that these nanomaterials—"pentablock copolymer micelles," according to the researchers' paper—helped B cells initiate antibody production. (Micelles are structures that self-assemble in water or oils as their molecules align because of their water-loving or water-hating properties.)

"From our studies, we understood very early on that these self-assembling micelles are different from the other types of adjuvants out there," Senapati said. "What we didn't know was the reason behind this unique type of immune response generated by them and that to me was the most intriguing part of this project."

Mallapragada said the researchers were able to tailor the chemistry of the nanomaterials, creating "micelles with added functionality."

One of those functions is the ability of positively charged micelles to associate with multiple antigens and directly interact with receptors on B cells, according to the paper. This cross-linking of the B cell receptors led to better antibody production and an enhanced immune response to a vaccine.

"These micelles act like a scaffold to cross-link two receptors," said Michael Wannemuehler, an associate director of the Nanovaccine Institute and an Iowa State professor of veterinary microbiology and preventive medicine.

He said the cross-link is strong and stable, like a ladder hooked at both ends, and is effective at stimulating antibody production by the B cells.

That cellular activation came without the inflammatory response that accompanies other vaccine adjuvants, potentially producing a "'just right' immune response" that could be "critical in the rational design of vaccines for older adults" who often suffer from chronic inflammation, according to the paper.

Making lab antibodies

Now that the researchers understood the "behind-the-scenes" mechanism of the micelles' antibody boost, Senapati said they wanted to see what else they could find.

"The next obvious step then was to test our hypothesis with antigens from some real-world pathogens and see if these micelles could be potentially used to produce antibodies against them," she said.

They used the micelle scaffolds to present antigens for SARS-CoV-2, the virus that causes COVID-19, and Yersinia pestis, the bacterium that causes pneumonic plague, to B cells in culture.

Those cells began generating "laboratory-scale quantities of therapeutic antibodies" against the two antigens, "further expanding the value of these nanomaterials to rapidly develop countermeasures against infectious diseases," according to the paper.

Those antibodies could potentially be used for diagnostic test kits or for treatments such as the monoclonal antibodies that have been developed to treat COVID-19, Wannemuehler said.

"There are different ways to produce antibodies," Narasimhan said. "The method we found is an alternative that could be quite powerful if it's generalized to other diseases. It could be a plug-and-play platform."

Because it's an effective vaccine adjuvant and antibody producer, the paper says the nanomaterial platform developed by the study team is "a highly versatile tool in the development of multiple countermeasures against emerging and reemerging infectious diseases."

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Explore further

Antibodies from original strain COVID-19 infection don't bind to variants

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More information: Sujata Senapati et al, Self-assembling synthetic nanoadjuvant scaffolds cross-link B cell receptors and represent new platform technology for therapeutic antibody production, Science Advances (2021). DOI: 10.1126/sciadv.abj1691

https://phys.org/news/2021-09-nanomaterial-aids-antibody-response.html

Why some people are less naturally resistant to COVID-19

 A large team of researchers affiliated with a host of institutions in the U.K. and Brazil has partially solved the mystery of why some people are less naturally resistant to COVID-19 than others. In their paper published in the journal Science, the group describes their study of the interferon system and the role it plays in combating the SARS-CoV-2 virus.

As the global pandemic has unfolded, it has become clear that some people have much more serious symptoms when contracting COVID-19 than others. Indeed, some people have been found to exhibit no symptoms at all, while others become so sick that they die. In this new effort, the researchers conducted extensive interferon-stimulated gene expression screening to isolate possible enzymes involved in alerting the immune system to an infection. Interferons are signaling proteins that alert the body when invasive entities such as bacteria and viruses are detected.

The work by the researchers led them to OAS1, an enzyme that reacts to interferon signaling by calling for an immune response when the SARS-CoV-2 virus is detected. Prior research has shown that OAS1 attaches to membranes using a prenyl group as part of the signaling process. Prior research has also shown that this signaling can inhibit replication of the SARS-CoV-2 virus. Noting its value in protecting people against COVID-19, the researchers looked at the transcriptomes of 500 COVID-19 patients who had experienced a wide range of symptoms and found that those who did not have prenylated OAS1 experienced much more severe symptoms. Why some people are born without the enzyme is still a mystery, but the work by the team could help lead to new types of vaccines against COVID-19 and other types of infections.

Intrigued by their findings, the researchers turned their attention to another mammal possibly involved in the pandemic—the horseshoe bat. They found it did not possess the form of prenylated OAS1 that protects humans from the virus, helping to explain why the virus is so deadly to that species. The finding could also help explain why the bats are such prolific hosts to a variety of viruses.

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Explore further

Sensor spies hideouts for ​virus replication inside cell membranes

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More information: Arthur Wickenhagen et al, A prenylated dsRNA sensor protects against severe COVID-19, Science (2021). DOI: 10.1126/science.abj3624

https://medicalxpress.com/news/2021-09-people-naturally-resistant-covid-.html

DHS concerned about potential border surge if COVID-19 restriction is partially lifted

 The Department of Homeland Security (DHS) is reportedly concerned about a potential increase in migrants trying to enter the U.S. if COVID-19 restrictions are partially lifted on Thursday.

NBC News reported on Thursday that Secretary Alejandro Mayorkas, during a phone call with senior DHS officials this week, asked if the department was ready for a potential surge of migrants attempting to cross the border in October, according to two DHS officials familiar with the conversation.

Personnel at the department is reportedly concerned about a possible influx of migrants if Title 42 — the policy the Biden administration has used amid the pandemic to return border crossers without giving them an opportunity to apply for asylum — is lifted, according to the DHS officials.

Federal District Judge Emmet Sullivan earlier this month ordered that the Biden administration stop using Title 42 to drive out families with children who cross the U.S.-Mexico border.

The ruling was handed down after families filed a class-action lawsuit arguing that the policy, which was crafted under the Trump administration, wrongly barred them from seeking humanitarian protections.

Sullivan’s ruling, which only applies to families, is set to take effect on Thursday, though the Biden administration has appealed the decision. More than 16,000 “individuals in a family unit” were expelled in August.

The Biden administration previously weighed nixing the measure by the end of July, according to NBC News, but ultimately decided against such a move. Officials were reportedly concerned that lifting it would cause a “catastrophic” migrant surge.

Two DHS officials told NBC News that the department is concerned that migrants may view the lifting of Title 42 as a green light to cross the border, and that they will be permitted to remain in the U.S. despite rulings on their asylum cases.

The concern within the department comes after the administration last week dealt with an unexpected influx of more than 25,000 Haitian migrants in Texas.

The camp where the migrants were staying has since been cleared, but photos circulated amid the chaos that depicted border officers on horseback trying to disperse the migrants.

Mayorkas said an investigation into the situation is underway.

https://thehill.com/policy/national-security/574740-dhs-concerned-about-potential-border-surge-if-covid-19-restriction