Glaxo rejects activist Elliott's demands for board and consumer business

 

GSK's board on Friday rejected Elliott's demands that the British company change its board and sell its consumer healthcare arm after separating it from its pharma business, a day after strongly worded proposals from the activist investor.

"The Board strongly believes Emma Walmsley is the right leader of New GSK and fully supports the actions being taken by her and the management team," GSK said on Friday, referring to the core pharmaceuticals and vaccine business.

It added that support for GSK's strategy and leadership was shown in talks with its largest shareholders.

In a letter to GSK's board, Elliott on Thursday said GSK should review its leadership and consider a sale of its consumer healthcare business as it confirmed it had taken a significant stake in the group.

Elliott demanded that directors with more "biopharmaceuticals and scientific experience" be added to GSK's board before the planned break-up of the company next year. That new board should then decide the best executive leadership, it added.

GSK responded by stating that governance and oversight had been strengthened with the appointment of two new non-executive directors over the last 18 months, and that more biopharmaceutical expertise was on its way with even more appointments, saying this had been flagged previously.

The British drugmaker also defended its decision to transfer majority ownership in the consumer business to its shareholders in a demerger, combined with plans to sell a minority stake in the business in the near future.

"The demerger structure reflects feedback from a significant proportion of GSK's shareholders that they wish to own Consumer Healthcare as a new listed entity," GSK wrote.

Elliott had urged GSK to look at a full sale of the consumer health business, which is a joint venture with Pfizer, should the opportunity arise.

https://www.marketscreener.com/quote/stock/PFIZER-INC-23365019/news/GSK-rejects-activist-Elliott-s-demands-for-board-and-consumer-business-35774874/

J&J COVID-19 vaccine shows promising early signs of protecting against Delta variant

 Johnson & Johnson’s COVID-19 vaccine showed promising signs in a small laboratory study of protecting against the Delta variant spreading across the U.S. and other countries, the company said.

In laboratory testing, the vaccine triggered strong levels of neutralizing antibodies in blood samples taken from eight vaccinated people, J&J said Thursday.

The positive performance adds to a growing set of evidence indicating currently authorized Covid-19 vaccines can safeguard against the Delta variant, which appears to be more contagious than earlier strains.

How well the J&J shot fares against the Delta variant has been closely watched by health authorities around the world.

Many countries have been counting on supplies, especially because the vaccine is simpler to ship, handle and store than the shots from Pfizer Inc. and its partner BioNTech SE and from Moderna Inc.

Ticker	Security	Last	Change	Change %
JNJ	JOHNSON & JOHNSON	165.96	+1.22	+0.74%
PFE	PFIZER INC.	39.56	+0.40	+1.02%
MRNA	MODERNA, INC.	235.11	+0.13	+0.06%
AZN	ASTRAZENECA PLC	60.31	+0.41	+0.68%

The new findings "reinforce the ability of the Johnson & Johnson COVID-19 vaccine to help protect the health of people globally," said J&J Chief Scientific Officer Paul Stoffels.

J&J also said its vaccine provides protection against COVID-19 for at least eight months, the most time that researchers were able to study the shot’s durability.

The Delta variant first emerged in India late last year. Since then, it has spread rapidly, becoming the most common strain of the COVID-19 virus in several countries, including the U.S.

The variant made up about 40% of positive COVID-19 test samples as of June 27, according to population genomics company Helix OpCo LLC, which collects and analyzes test samples from several U.S. states.

Vaccination is the best defense against the Delta variant, according to public-health authorities, who have cited the threat posed by the strain in urging people to get immunized.

So far, studies have indicated various vaccines appear effective against the Delta strain, especially once individuals have been fully vaccinated, though the shots aren’t as protective as they are against the original virus.

Separate studies in England and Scotland found that vaccines from Pfizer-BioNTech and AstraZeneca PLC offered substantial protection from the Delta variant against severe cases of Covid-19 and hospitalization.

England’s public health agency said an analysis of 14,000 cases found the Pfizer-BioNTech shot reduced the risk of hospitalization after infection with Delta by 96%.

J&J’s single-dose shot is based on a different technology than the Pfizer-BioNTech and Moderna vaccines, but operates similar to AstraZeneca’s.

J&J’s shot uses a modified version of the virus responsible for the common cold, to carry genetic instructions teaching cells how to make the spike protein that juts from the surface of the coronavirus.

Production of the spike protein, in turn, prompts the immune system to develop molecular defenses against the coronavirus.

In its large, pivotal study, the J&J vaccine was 66% effective in protecting against severe disease, though it appeared to be less effective against the variant first found in South Africa, now called Beta.

Overall, however, it was highly effective in places where variants were spreading during the trial. The U.S. Food and Drug Administration authorized the shot in February.

J&J said the neutralizing-antibody activity found in its recent laboratory study was higher for the Delta variant than for Beta.

https://www.foxbusiness.com/healthcare/jj-covid-19-vaccine-shows-promising-preliminary-signs-of-protecting-against-delta-variant

New Study Links 'Acute Chest Pain' In Male Soldiers To mRNA Vaccines

 More research has been published highlighting more problematic side effects linked to COVID-19 shots. Last week, we published our latest update on rare cases of heart inflammation that have been linked to the mRNA COVID jabs, including the jabs from Pfizer-BioNTech and Moderna. After a hurried secret meeting with its advisory board on vaccine safety, the FDA reluctantly release a warning asking patients experiencing these symptoms to seek help immediately.

The latest study, published in JAMA's Cardiology Journal on Tuesday, showed that 23 male soldiers (including 22 who were deemed "previously health") between the ages of 20 and 51 presented "acute onset of marked chest pain" within four days of receiving their second dose. Patients who sought care for chest pain in the military health-care system following COVID-19 vaccination and were subsequently diagnosed with clinical myocarditis were included in the case study.

All the members who tested for myocarditis (for those who aren't familiar with it, myocarditis is a condition that causes the swelling of the heart muscle and can cause difficulty breathing, heart failure, and death) were all "physically fit by military standards and lacking any known history of cardiac disease, significant cardiac risk factors, or exposure to cardiotoxic agents."

All of the patients whose data was included in the study underwent electrocardiography and echocardiography tests. Abnormal electrocardiography findings were recorded in 19 patients (83%): findings included ST-segment elevations, T-wave inversions, and nonspecific ST changes. Echocardiography in 4 patients (17%) demonstrated reduced left ventricular ejection fractions (40% to 50%).

The cardiac symptoms faded within a week of onset for 16 patients, while 7 others continued to have chest discomfort at the time of this report; follow-up is ongoing.

As one table from the study showed, the number of cases of heart inflammation reported in the military is much higher than the rate that one might expect given population-wide incidence of these symptoms. This suggests some new variable is likely causing the surge in cases.

The study's authors concluded that while the overall risk for patients who received an mRNA vaccine remains extremely small, the US isn't alone in discovering these cases. Israel, which also relied on mostly on mRNA vaccines to  inoculate its population, is also seeing surprisingly high incidence of heart inflammation that's likely linked to the vaccines.

https://www.zerohedge.com/covid-19/new-study-shows-dangerous-hearth-inflammation-likely-tied-pfizer-moderna-jabs

Leonard Green-backed WCG files for U.S. IPO

 WCG Clinical Inc, a clinical trial solutions company backed by buyout firm Leonard Green & Partners LP, on Thursday filed for an initial public offering in the United States. 

https://finance.yahoo.com/news/leonard-green-backed-wcg-files-204711521.html

Nearly 5 out of 6 coronavirus cases were undetected in pandemic’s early months

 Scientists at the National Institutes of Health who studied blood samples from across the United States have discovered that for every coronavirus infection recorded during the spring and summer of 2020, nearly five more went undetected — amounting to nearly 17 million additional cases by July 2020.

The discovery, published this week in the journal Science Translational Medicine, reveals that the coronavirus was far more widespread in the early months of the COVID-19 pandemic than previously thought, and could help scientists and health officials better respond to future outbreaks.

At the beginning of the pandemic, experts realized many infections were slipping under the radar. But without the means to implement a comprehensive testing program, the extent of the undercount was unknown, said Dr. Ellen Foxman, an immunologist at Yale University.

“That was the big question: For each infection that we actually do diagnose, how many are we not diagnosing?” said Foxman, who was not involved in the new research.

Many studies attempted to tackle this question in various ways. “But the problem is a lot of them had a very specific, small population that was being looked at,” she said — a cruise ship, say, or a shelter.

A team of immunologists, engineers, clinicians and statisticians across the NIH worked together to try and get a better handle on the number of undiagnosed coronavirus infections by looking for antibodies in blood samples. If antibodies to SARS-CoV-2 were present, it would be an irrefutable sign that the person’s immune system had encountered the virus.

Some of the researchers fine-tuned a mail-in test kit system that allowed participants to collect their own blood at home instead of having to visit a clinic for a blood draw. Volunteers used a lancet to prick their fingertip and squeeze out droplets of blood that they deposited into sampling devices. The dried blood spots could then be mailed to the NIH, where the samples were screened for antibodies.

This user-friendly mail-in format meant the scientists could gather samples from far and wide, said Kaitlyn Sadtler, an immunologist and bioengineer at the NIH’s National Institute of Biomedical Imaging and Bioengineering and one of the paper’s senior authors.

“We had samples from Alaska, we had samples from Hawaii,” Sadtler said. Basically, “if a delivery truck can make it to your house, we could get a sample from you.”

The scientists had planned to recruit about 10,000 participants. Thanks to publicity about the work, they ended up with more than 240,000 volunteers — far more than they could feasibly study. So they used the demographic and geographic information the volunteers provided to select a group that was representative of the county’s population based on the U.S. census.

The scientists sent out about 11,000 kits over late spring and summer and received just over 9,000 back, most of them between May 10 and July 31. About 1,000 had incomplete information, but the rest could be analyzed.

The results: By last summer, after the first wave of the pandemic, there were roughly 16.8 million undiagnosed coronavirus infections in addition to the roughly 3 million that were confirmed. The researchers calculated that for every infection that had been officially tallied, about 4.8 others were uncounted.

With a more complete picture of coronavirus infections, the research team reported that:

• Antibody presence was far higher in women (5.5%) than in men (3.5%).
• Black Americans had the highest rate of past infection (14.2%), followed by Native American/Alaska Native (6.8%), Latino (6.1%), white (2.5%) and Asian (2%) volunteers.
• The youngest of the adult participants — those between age 18 and 44 — had the highest antibody prevalence (5.9%).
• People living in urban areas were far more likely to have antibodies (5.3%) compared with those from rural areas (1.1%).
• People in the mid-Atlantic and Northeast regions had the highest antibody prevalence (8.6% and 7.5%, respectively), while the lowest rate was in the Midwest (1.6%).

The study shows that these differences exist, not why they emerge. But experts are weighing possible explanations for at least a few of these trends — some biological, some behavioral and some systemic.

For example, it’s possible that many younger people who were infected didn’t realize it because, unlike with older adults, they didn’t get especially sick. It’s also possible that younger people were more likely to be out in public and interacting with others, giving them more opportunity to encounter the virus.

The higher antibody rate in densely populated urban areas came as little surprise. The higher prevalence in the mid-Atlantic and Northeast regions also tracks, since they were the first areas to experience serious outbreaks.

As for the higher antibody prevalence among Black Americans and other people of color: This probably reflects long-standing healthcare disparities that the pandemic made even more apparent.

“We see this pattern also in diagnosed cases and deaths, and it is a reflection of inequities that prevent equal access to diagnostics, care, and treatment,” Sadtler said.

Does the recognition of all these previously overlooked cases mean the country is closer to reaching herd immunity than previously thought?

Not necessarily, Sadtler said. It’s unknown how long the immunity gained from a coronavirus infection lasts, and whether this so-called natural immunity offers strong protection against an array of viral variants. (That’s a big concern now that the Delta variant, which may be twice as transmissible as the conventional strain, is spreading in the U.S.)

“Vaccines induce a very high level of antibodies — so, much stronger immunity than a previous infection,” she said. “We still need to make sure that everybody gets vaccinated, so everybody has strong and long-lasting immunity.”

Sadtler said the team is continuing to analyze follow-up samples sent in by the same group of participants, in the hopes of seeing whether any of them had a second coronavirus infection by January or February of this year.

https://www.latimes.com/science/story/2021-06-25/nearly-5-out-of-6-coronavirus-cases-were-undetected-early-in-pandemic

Study: Immunocompromised Response to COVID-19 Vaccination

 People with conditions that compromise their immune systems exhibit a wide spectrum of antibody responses to COVID-19 vaccination, ranging from only 1 in 5 lung transplant patients having an antibody response to a nearly complete response in patients with well-controlled HIV. The results are part of an interim analysis of a large study on UPMC patients and health care workers. 

 

The study is one of the first to verify that the ability of blood from immunocompromised participants to neutralize the virus closely mirrors their antibody levels measured by a Food and Drug Administration (FDA)-approved test, meaning that antibody testing is a good proxy for neutralizing titers. 

 

In an effort to share crucial information to guide clinical and public health decisions, UPMC and University of Pittsburgh School of Medicine physician-scientists published the findings today in medRxiv, a preprint journal, and announced the results ahead of peer-reviewed publication. 

 

“Our study highlights the urgent need to optimize and individualize COVID-19 prevention in patients with immunocompromising conditions and have other treatments—such as monoclonal antibodies—available should vaccination fail,” said lead author Ghady Haidar, M.D., UPMC transplant infectious diseases physician and assistant professor in Pitt’s Division of Infectious Diseases. “Given the Centers for Disease Control and Prevention’s recommendations permitting vaccinated people to abandon masking and social distancing in most settings, our findings also have implications for public health guidance, since nearly 4% of Americans are immunocompromised.”

 

Between April 14 and June 14, the UPMC-Pitt team tested blood samples from 107 healthy volunteer health care workers and 489 immunocompromised patients who had completed COVID-19 vaccination as part of the COVID-19 Vaccine in the Immunocompromised Study (CoVICS). The immunocompromised patients included those who had a solid organ transplant, an autoimmune disorder, blood cancer, a solid tumor cancer or HIV. 

 

Antibodies are proteins that block invading pathogens—such as SARS-CoV-2, the virus that causes COVID-19—from infecting cells. They are produced by the immune system in response to vaccination. 

 

While 98.1% of the health care workers produced antibodies after vaccination, only 37.2% of the vaccinated solid organ transplant patients were positive for antibodies; 54.7% of the blood cancer patients; 82.4% of those with solid tumor cancer and 83.8% of patients with autoimmune disorders. In contrast, 94.6% of patients with HIV made antibodies.

 

Among patients with solid organ transplants, lung transplant patients had a particularly poor response to vaccination, with only 22.2% producing antibodies. Liver transplant patients fared best, with 60.6% of study participants producing antibodies after vaccination. Patients who received their transplant less than a year ago were less likely to respond to vaccination than those transplanted earlier. 

 

In addition, cancer patients receiving radiation therapy and patients taking certain medications—such as antimetabolites for transplant and anti-CD20 monoclonal antibodies for autoimmune disorders—were more likely not to produce antibodies after COVID-19 vaccination. 

 

The researchers then took blood sera, the amber-colored, protein-rich liquid that separates out when blood coagulates, from a subset of the participants—30 health care workers and 36 immunocompromised patients—and tested it for its ability to neutralize SARS-CoV-2 pseudovirus. They found that the ability of the participants’ sera to neutralize the virus correlated strongly with their antibody levels measured by an independent FDA-approved test.

 

“This is important because we’ve seen several studies indicating that immunocompromised people are less likely to produce antibodies in response to COVID-19 vaccination,” said senior author John Mellors, M.D., chief of the Division of Infectious Diseases at UPMC and Distinguished Professor of Medicine at Pitt. “And we can assume this means they’re less likely to be able to fight the virus, but until we were able to test for virus neutralization, that was only an assumption. Our results give us more confidence in saying that people who do not produce antibodies truly are at greater risk of COVID-19 infection and that the level of antibodies produced is a proxy for ability to neutralize the virus.”

 

However, the physician-scientists stressed that the immune system has more tools than antibodies at its disposal, including T-cells and other immune cells, which may provide some level of immunity. So, while it is concerning when someone gets a negative antibody test, it is still possible for the immune system to fight off the virus, even if vaccination does not produce antibodies, Mellors said. 

 

The Centers for Disease Control and Prevention, FDA, American Society of Transplantation and several national cancer associations, among others, recommend against routine antibody testing after vaccination, and UPMC currently does not offer it outside of a research study or clinical indication.  

 

“At this point, clinical advice does not change for immunocompromised people, whether an antibody test is positive or negative,” said Haidar. “They should still wear a mask in public, practice social distancing, get vaccinated and encourage those around them to be vaccinated. A positive antibody test does not give us certainty that they are protected against the virus, and the risk of COVID-19 causing serious complications and death still exists.”

 

Additional authors on this research are Mounzer Agha, M.D., Amy Lukanski, D.N.P., Kelsey Linstrum, M.S., Rachel Troyan, M.B.A., Andrew Bilderback, M.S., Scott Rothenberger, Ph.D., Deborah K. McMahon, M.D., Melissa Crandall, M.B.A., P. Nathan Enick, B.S., Michelle Sobolewski, M.S., Kevin Collins, M.B.A., Marc B. Schwartz, M.D., Jeffrey M. Dueker, M.D., Fernanda P. Silveira, M.D., Mary E. Keebler, M.D., Abhinav Humar, M.D., James D. Luketich, M.D., Matthew R. Morrell, M.D., Joseph M. Pilewski, M.D., John F. McDyer, M.D., Bhanu Pappu, Ph.D., Robert L. Ferris, M.D., Stanley M. Marks, M.D., Cynthia Klamar-Blain, Urvi M. Parikh, Ph.D., Amy Heaps, M.S., Paula L. Kip, Ph.D., Alan Wells, M.D., Tami Minnier, M.S., and Derek Angus, M.D., all of Pitt, UPMC or both. 

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PHOTO INFO: (click images for high-res versions)

 

CREDIT BOTH: UPMC

 

Top:

CAPTION: Ghady Haidar, M.D., UPMC transplant infectious diseases physician and assistant professor, University of Pittsburgh Division of Infectious Diseases.

 

Bottom:

CAPTION: John Mellors, M.D., chief of the Division of Infectious Diseases at UPMC and Distinguished Professor of Medicine, University of Pittsburgh.

https://www.upmc.com/media/news/063021-haidar-covics-interim-medrxiv

Targeting m6A RNA modification pathway blocks SARS-CoV-2 and HCoV-OC43 replication

 

Hannah M. Burgess1, 

Daniel P. Depledge2, 

Letitia Thompson1, 

Kalanghad Puthankalam Srinivas1, 

Rebecca C. Grande1, 

Elizabeth I. Vink1, 

Jonathan S. Abebe2, 

Wesley P. Blackaby3, 

Alan Hendrick3, 

Mark R. Albertella3, 

Tony Kouzarides4, 

Kenneth A. Stapleford1, 

Angus C. Wilson1 and 

Ian Mohr1

doi:10.1101/gad.348320.121
PDF: http://genesdev.cshlp.org/content/early/2021/06/22/gad.348320.121.full.pdf+html

Abstract

N⁶-methyladenosine (m⁶A) is an abundant internal RNA modification, influencing transcript fate and function in uninfected and virus-infected cells. Installation of m⁶A by the nuclear RNA methyltransferase METTL3 occurs cotranscriptionally; however, the genomes of some cytoplasmic RNA viruses are also m⁶A-modified. How the cellular m⁶A modification machinery impacts coronavirus replication, which occurs exclusively in the cytoplasm, is unknown. Here we show that replication of SARS-CoV-2, the agent responsible for the COVID-19 pandemic, and a seasonal human β-coronavirus HCoV-OC43, can be suppressed by depletion of METTL3 or cytoplasmic m⁶A reader proteins YTHDF1 and YTHDF3 and by a highly specific small molecule METTL3 inhibitor. Reduction of infectious titer correlates with decreased synthesis of viral RNAs and the essential nucleocapsid (N) protein. Sites of m⁶A modification on genomic and subgenomic RNAs of both viruses were mapped by methylated RNA immunoprecipitation sequencing (meRIP-seq). Levels of host factors involved in m⁶A installation, removal, and recognition were unchanged by HCoV-OC43 infection; however, nuclear localization of METTL3 and cytoplasmic m⁶A readers YTHDF1 and YTHDF2 increased. This establishes that coronavirus RNAs are m⁶A-modified and host m⁶A pathway components control β-coronavirus replication. Moreover, it illustrates the therapeutic potential of targeting the m⁶A pathway to restrict coronavirus reproduction.

http://genesdev.cshlp.org/content/early/2021/06/22/gad.348320.121.abstract