Former Aetna Inc. Chief Executive Mark Bertolini said he is being pushed off the board of CVS Health Corp.
Mr. Bertolini, who joined the CVS board after the November 2018
closing of CVS’s nearly $70 billion deal to buy Aetna, told The Wall
Street Journal he was willing to stay on the board, and he said the
integration between the two companies isn’t complete.
CVS said Monday that Mr. Bertolini and two other directors won’t
stand for reelection to the board. The company said Mr. Bertolini would
depart “following the successful integration of the Aetna business.”
The company said it was reducing the number of board members following corporate governance best practices.
CVS Chairman David Dorman said in a statement announcing the changes
that the board wished to thank Mr. Bertolini “for his contribution to
the successful integration of Aetna.” He said the remaining board
members had strong confidence in CVS’s leadership and direction.
Mr. Bertolini said, “I was willing to continue to serve on the board
of directors in support of the most transformative effort in health care
for our nation. However, the board thought otherwise.” He said the
“integration is far from over.”
Asked about his relationship with current CVS Chief Executive Officer
Larry Merlo, he said, “There’s always going to be a natural tension
between the current CEO and the former CEO in any discussions regarding
how you move the strategy forward. He’s the guy in the seat, I’m not.”
A spokesman for CVS said, “As Dave Dorman said, the integration has
been a success and the board has the utmost confidence in the current
management team and the progress the combined company has shown to date.
We will of course have more to share on that front when we report
earnings next week.”
After the departures, CVS said its board membership will shrink to 13
from 16. In addition to Mr. Bertolini, the company said that Richard
Swift and Richard Bracken won’t stand for reelection to the board and
will leave after the company’s annual meeting. The date of this year’s
annual meeting hasn’t yet been announced, but the meeting was in May
last year.
The company’s 2018 merger created an industry giant that brings
together retail pharmacy, a pharmacy-benefit manager and the Aetna
insurance business. CVS has said it expects the combination to improve
health care and bring down costs
CVS shares fell sharply last year after a downbeat earnings
projection in February. Investors pressed for more detail about the
company’s growth plans, and CVS promised that it would return to profit
growth this year. Shares rose as the company delivered
stronger-than-expected results in subsequent quarters.
Matthew Borsch, an analyst with BMO Capital Markets, said investors’ mood around CVS is brighter.
Yet, he said, Mr. Bertolini’s unusual public statement, combined with
the recent departure of the company’s president of pharmacy, might
“raise questions about whether everything is going as well as management
insists.”
CVS is in the process of opening around 1,500 health hub stores,
which are designed to offer a broader range of services than its
traditional drugstores, many aimed at people with chronic illnesses such
as diabetes.
Yet CVS, like competitor Walgreens Boots Alliance Inc., faces
pressure on margins in its retail pharmacy business. Also, investors
have pushed down shares of insurers over political concerns, as
Democratic presidential candidates advocate for a major revamp of the
U.S. health-care system.
https://www.marketscreener.com/CVS-HEALTH-CORPORATION-12230/news/Former-Aetna-CEO-Mark-Bertolini-Says-He-Is-Being-Pushed-Off-CVS-Board-Update-29934116/
Monday, February 3, 2020
Quick retraction of a faulty coronavirus paper was a good moment for science
As fears of the novel coronavirus 2019-nCoV
continued to spread last Friday, an inflammatory new paper appeared on
bioRxiv, a preprint server, where scientists post work that hasn’t been
vetted.
Titled “Uncanny similarity of unique inserts in the 2019-nCoV spike protein to HIV-1 gp120 and Gag,” the paper claimed to find similarities between the new coronavirus and HIV, the virus that causes AIDS. The use of the word “uncanny” in the title, together with “unlikely to be fortuitous” in the abstract, led some to think that the authors were suggesting the virus had somehow been engineered by humans.
The paper, from academic institutions in New Delhi, India, was critical and alarming, if true. Except that it wasn’t.
The paper was almost immediately withdrawn, but not before plenty of
handwringing from researchers who complained that the appearance of such
shoddy work on a preprint server without vetting by peer reviewers is
precisely why the hoary old model of science publishing is better at
keeping junk science out of the literature.
Except that’s not true, either. The old model has its advantages, to be sure, but it, too, is prone to the menace of pseudoscience, bad data, and other flaws — despite traditional academic journals’ army of peer reviewers. And when these publications publish bad or erroneous research, it can take months or years for the papers to be corrected or retracted — if they ever are.
In contrast, the reaction from the scientific community to the bioRxiv paper was swift. In a nutshell, commenters on bioRxiv and Twitter said, the author’s methods seemed rushed, and the findings were at most a coincidence. By Saturday morning, bioRxiv had placed a special warning on all papers about coronavirus. Later Saturday, the authors commented on their paper, saying they were withdrawing it. And on Sunday, a more formal retraction appeared: “This paper has been withdrawn by its authors. They intend to revise it in response to comments received from the research community on their technical approach and their interpretation of the results.”
All of that happened before a single news outlet with any reach covered the paper, as best we can tell. But none of it was quite fast enough for some critics. “This is why preprints can be bad,” said one scientist on Twitter. That scientist, Michael Shiloh, said he had even used bioRxiv to post preprints. “What bugs me about this preprint is that had this manuscript undergone legitimate peer review, these flaws would have led to a swift rejection and it wouldn’t be contributing to the conspiracy theories and fear surrounding this outbreak,” Shiloh continued.
History suggests that Shiloh’s confidence in peer review’s ability to suss out pseudoscience may be a bit misplaced. The fraudulent 1998 paper that set off the vaccine-autism scare was published in The Lancet, one of the world’s leading peer-reviewed medical journals. Other examples — including a paper by an intelligent design advocate questioning the validity of the second law of thermodynamics as it pertained to evolution — abound. Papers claiming a link between autism and vaccines pop up nearly every year.
And even when peer-reviewed journals do realize they’ve been had, retractions can take months or years. The Lancet took 12 years. Another journal took five years to retract a paper claiming that HIV did not cause AIDS. We could go on, and the list includes papers that have never even been corrected.
Those who claim preprint servers are dangerous because they lack peer review — bioRxiv has a perfunctory screening process — sometimes acknowledge that journals have had to speed up their game to meet the pressures of an outbreak like coronavirus, or SARS in the early part of this century. Angela Cochran, president of the Society for Scholarly Publishing, a trade group for publishers, said on Twitter: “Earlier this week, folks celebrated that coronavirus papers were popping up in preprint servers. Now there is a reminder not to use them to guide clinical practice because they haven’t been reviewed. Journals ARE reviewing coronavirus papers and getting [them] pub’d quickly.”
Kent Anderson, another publishing industry veteran, put it more bluntly: “Journals Win The Coronavirus Race.”
Publishers have been looking for ways to score points against — and shut down — preprints for at least half a century. Journals have speedily published a number of important papers on the new coronavirus already, no doubt. Publishing industry champions are often quick to say that speedy peer review does not mean sloppy peer review — even in cases that require massive corrections.
But those same champions are often unwilling — with some notable and welcome exceptions — to acknowledge how slow and ineffective correction in science can be. Doing so might, after all, make some people question the expensive subscription deals universities agree to with publishers, as well as the article processing charges that can run into the thousands of dollars for open access publications.
Peer review can add a valuable filter. But those who work in publishing seem to be so wedded to the existing process that they can’t admit its flaws — or that it might be a good idea to also embrace preprint servers that could upend their business models. Just like in politics, maybe it’s time to agree that the publishing process is a messy one, and stop using single episodes, free of context, to score points against one’s rivals.
Titled “Uncanny similarity of unique inserts in the 2019-nCoV spike protein to HIV-1 gp120 and Gag,” the paper claimed to find similarities between the new coronavirus and HIV, the virus that causes AIDS. The use of the word “uncanny” in the title, together with “unlikely to be fortuitous” in the abstract, led some to think that the authors were suggesting the virus had somehow been engineered by humans.
The paper, from academic institutions in New Delhi, India, was critical and alarming, if true. Except that it wasn’t.
Except that’s not true, either. The old model has its advantages, to be sure, but it, too, is prone to the menace of pseudoscience, bad data, and other flaws — despite traditional academic journals’ army of peer reviewers. And when these publications publish bad or erroneous research, it can take months or years for the papers to be corrected or retracted — if they ever are.
In contrast, the reaction from the scientific community to the bioRxiv paper was swift. In a nutshell, commenters on bioRxiv and Twitter said, the author’s methods seemed rushed, and the findings were at most a coincidence. By Saturday morning, bioRxiv had placed a special warning on all papers about coronavirus. Later Saturday, the authors commented on their paper, saying they were withdrawing it. And on Sunday, a more formal retraction appeared: “This paper has been withdrawn by its authors. They intend to revise it in response to comments received from the research community on their technical approach and their interpretation of the results.”
All of that happened before a single news outlet with any reach covered the paper, as best we can tell. But none of it was quite fast enough for some critics. “This is why preprints can be bad,” said one scientist on Twitter. That scientist, Michael Shiloh, said he had even used bioRxiv to post preprints. “What bugs me about this preprint is that had this manuscript undergone legitimate peer review, these flaws would have led to a swift rejection and it wouldn’t be contributing to the conspiracy theories and fear surrounding this outbreak,” Shiloh continued.
History suggests that Shiloh’s confidence in peer review’s ability to suss out pseudoscience may be a bit misplaced. The fraudulent 1998 paper that set off the vaccine-autism scare was published in The Lancet, one of the world’s leading peer-reviewed medical journals. Other examples — including a paper by an intelligent design advocate questioning the validity of the second law of thermodynamics as it pertained to evolution — abound. Papers claiming a link between autism and vaccines pop up nearly every year.
And even when peer-reviewed journals do realize they’ve been had, retractions can take months or years. The Lancet took 12 years. Another journal took five years to retract a paper claiming that HIV did not cause AIDS. We could go on, and the list includes papers that have never even been corrected.
Those who claim preprint servers are dangerous because they lack peer review — bioRxiv has a perfunctory screening process — sometimes acknowledge that journals have had to speed up their game to meet the pressures of an outbreak like coronavirus, or SARS in the early part of this century. Angela Cochran, president of the Society for Scholarly Publishing, a trade group for publishers, said on Twitter: “Earlier this week, folks celebrated that coronavirus papers were popping up in preprint servers. Now there is a reminder not to use them to guide clinical practice because they haven’t been reviewed. Journals ARE reviewing coronavirus papers and getting [them] pub’d quickly.”
Kent Anderson, another publishing industry veteran, put it more bluntly: “Journals Win The Coronavirus Race.”
Publishers have been looking for ways to score points against — and shut down — preprints for at least half a century. Journals have speedily published a number of important papers on the new coronavirus already, no doubt. Publishing industry champions are often quick to say that speedy peer review does not mean sloppy peer review — even in cases that require massive corrections.
But those same champions are often unwilling — with some notable and welcome exceptions — to acknowledge how slow and ineffective correction in science can be. Doing so might, after all, make some people question the expensive subscription deals universities agree to with publishers, as well as the article processing charges that can run into the thousands of dollars for open access publications.
Peer review can add a valuable filter. But those who work in publishing seem to be so wedded to the existing process that they can’t admit its flaws — or that it might be a good idea to also embrace preprint servers that could upend their business models. Just like in politics, maybe it’s time to agree that the publishing process is a messy one, and stop using single episodes, free of context, to score points against one’s rivals.
Quick retraction of a faulty coronavirus paper was a good moment for science
One Medical parent 1Life Healthcare’s stock soars in early trades
Shares of 1Life Healthcare Inc. ONEM, +6.57%
soared 38% in their trading debut Friday, after the company, which
operates under the name One Medical, priced its initial public offering
at the low end of its range. The primary-care provider sold 17.5 million
shares priced at $14 to raise $245 million. Shares are trading on the
Nasdaq under the ticker symbol “ONEM.” JP Morgan and Morgan Stanley were
lead bookrunning managers.
https://www.marketwatch.com/story/one-medical-parent-1life-healthcares-stock-soars-38-in-early-trade-2020-01-31
https://www.marketwatch.com/story/one-medical-parent-1life-healthcares-stock-soars-38-in-early-trade-2020-01-31
Stifel Starts AdaptHealth (AHCO) at Buy
Stifel analyst Mathew Blackman initiates coverage on AdaptHealth (NASDAQ: AHCO) with a Buy rating and a price target of $17.00.
https://www.streetinsider.com/Analyst+Comments/Stifel+Starts+AdaptHealth+%28AHCO%29+at+Buy/16395014.html
https://www.streetinsider.com/Analyst+Comments/Stifel+Starts+AdaptHealth+%28AHCO%29+at+Buy/16395014.html
Passage Bio on deck for IPO
The Philadelphia-based biotech develops gene therapies to treat rare single-gene disorders affecting the central nervous system.
Lead candidates are: PBGM01 for GM1 gangliosidosis, PBFT02 for frontotemporal dementia and PBKR03 for Krabbe disease.
One of the founders is University of Pennsylvania’s James Wilson, a pioneer in gene therapies.
2019 Financials: Operating Expenses: $37.2M (+176%); Net Loss: ($45.6M) (-256%); Cash Burn: ($39.9M) (-115%).
https://seekingalpha.com/news/3537426-passage-bio-on-deck-for-ipoNovel compound is promising drug candidate for Alzheimer’s
A newly identified compound is a promising candidate for inhibiting
the production of amyloids, the abnormal proteins that form toxic
clumps, called fibrils, inside the brains of patients with Alzheimer’s
disease. As published today in the Royal Society of Chemistry’s Chemical Communications, the compound—known as “C1″—uses a novel mechanism to efficiently prevent the enzyme gamma-secretase from producing amyloids.
Amyloid fibrils are largely composed of the peptide Amyloid beta, which is produced when enzymes, including gamma secretase, make cuts to the amyloid precursor protein found in high concentrations the membrane of brain cells. C1 is a covalent gamma-secretase inhibitor that blocks the active site on the precursor protein where gamma-secretase would bind to transform it into amyloids, rather than—as traditional enzyme inhibitors do—blocking the active site on gamma-secretase itself.
“Historically, drug trials for gamma secretase inhibitors failed because traditional enzyme inhibitors have severe side effects. They stopped all of the normal functions of gamma secretase,” said Chunyu Wang, a professor of biological sciences and member of the Center for Biotechnology and Interdisciplinary Studies (CBIS) at Rensselaer Polytechnic Institute. “Our compound binds to the cleavage site of the precursor protein instead of the enzyme itself, which may avoid many problems associated with traditional enzyme inhibitors.”
In 2018, with support from the Warren Alpert Foundation, Wang began screening drugs to identify a compound that targets the amyloid precursor protein substrate, which would block the activity of gamma secretase involved in amyloid production while allowing all other functions. He began the search with “in silico screening,” using computer modeling to test tens of millions of compounds.
C1 was one of several candidates to emerge from that screening. As described in the paper, C1 blocks amyloid production with high efficiency when present at micromolar concentrations, both in test tubes and in cell culture. The research is patent pending.
C1 is a covalent inhibitor, meaning it forms a chemical bond with its target. Wang said that because of their permanent bond, covalent inhibitors are more durable than their non-covalent counterparts. Covalent inhibitors make up about one-third of the drug market, even though they have traditionally been viewed as having a higher risk of causing immune reactivity. In recent years, there is surge in the development of covalent inhibitors, as more highly specific covalent inhibitors showed excellent efficacy towards challenging drug targets.
“With a new approach to tackling the principal pathology of Alzheimer’s disease, Chunyu’s work is generating a fresh roster of drug candidates with enormous promise,” said Deepak Vashishth, the director of CBIS. “His works speaks to the power of the interdisciplinary culture of research at CBIS, and we are pleased with this early result.”
Amyloid fibrils are largely composed of the peptide Amyloid beta, which is produced when enzymes, including gamma secretase, make cuts to the amyloid precursor protein found in high concentrations the membrane of brain cells. C1 is a covalent gamma-secretase inhibitor that blocks the active site on the precursor protein where gamma-secretase would bind to transform it into amyloids, rather than—as traditional enzyme inhibitors do—blocking the active site on gamma-secretase itself.
“Historically, drug trials for gamma secretase inhibitors failed because traditional enzyme inhibitors have severe side effects. They stopped all of the normal functions of gamma secretase,” said Chunyu Wang, a professor of biological sciences and member of the Center for Biotechnology and Interdisciplinary Studies (CBIS) at Rensselaer Polytechnic Institute. “Our compound binds to the cleavage site of the precursor protein instead of the enzyme itself, which may avoid many problems associated with traditional enzyme inhibitors.”
In 2018, with support from the Warren Alpert Foundation, Wang began screening drugs to identify a compound that targets the amyloid precursor protein substrate, which would block the activity of gamma secretase involved in amyloid production while allowing all other functions. He began the search with “in silico screening,” using computer modeling to test tens of millions of compounds.
C1 was one of several candidates to emerge from that screening. As described in the paper, C1 blocks amyloid production with high efficiency when present at micromolar concentrations, both in test tubes and in cell culture. The research is patent pending.
C1 is a covalent inhibitor, meaning it forms a chemical bond with its target. Wang said that because of their permanent bond, covalent inhibitors are more durable than their non-covalent counterparts. Covalent inhibitors make up about one-third of the drug market, even though they have traditionally been viewed as having a higher risk of causing immune reactivity. In recent years, there is surge in the development of covalent inhibitors, as more highly specific covalent inhibitors showed excellent efficacy towards challenging drug targets.
“With a new approach to tackling the principal pathology of Alzheimer’s disease, Chunyu’s work is generating a fresh roster of drug candidates with enormous promise,” said Deepak Vashishth, the director of CBIS. “His works speaks to the power of the interdisciplinary culture of research at CBIS, and we are pleased with this early result.”
More information: “Substrate Interaction Inhibits gamma-secretase Production of Amyloid-B peptides,” Chemical Communications (2020).
Zika vaccine induces potent Zika and dengue cross-neutralizing antibodies
A new study led by scientists at the Walter Reed Army Institute of
Research has shown for the first time that a single dose of an
experimental Zika vaccine in a dengue-experienced individual can boost
pre-existing flavivirus immunity and elicit protective
cross-neutralizing antibody responses against both Zika and dengue
viruses. Findings were published today in Nature Medicine.
Researchers analyzed the antibody responses of a dengue-experienced volunteer who participated in a Phase 1 clinical trial of the WRAIR-developed Zika purified inactivated virus vaccine. They identified a potent cross-reactive antibody called MZ4 that demonstrated a potent ability to neutralize the Zika virus as well as the dengue virus serotype-2 strain. In addition, MZ4 protected against Zika and dengue in a mouse model of infection.
“Rapid-onset countermeasures are needed to protect military personnel, travelers and residents in areas where emerging infections such as Zika and dengue viruses are already widespread and expanding,” said Dr. Kayvon Modjarrad, who leads the U.S. Army Zika vaccine program, directs the Emerging Infectious Diseases Branch at WRAIR and is one of the lead authors on the paper. “These results demonstrate the potential for MZ4 to be part of the prevention toolbox for these diseases.”
The individual’s immune profile was compared to trial volunteers who had no previous exposure to dengue virus. While the volunteer with prior dengue exposure experienced a sharp increase in antibodies that neutralize Zika and dengue viruses, following just one dose of the ZPIV vaccine, the dengue-naïve trial participants required two vaccinations to reach a similar magnitude of Zika antibody responses. Additionally, no cross-reactive antibody response to dengue virus.
“These new findings indicate that an effective Zika vaccine could both boost dengue virus immune responses and generate potent Zika neutralizing antibodies that might have unique potential as a prevention tool in regions where both dengue and Zika are prevalent,” said Dr. Shelly Krebs, a B cell researcher at WRAIR and senior author of the paper.
Building on these findings, researchers used samples from another Phase 1 study of the ZPIV vaccine currently being conducted in Puerto Rico, where there is a higher risk of exposure to flaviviruses, a family of viruses that includes Zika, dengue, Japanese encephalitis, yellow fever and West Nile viruses. WRAIR researchers found that vaccination with ZPIV in Puerto Rican individuals with prior flavivirus-experience yielded similar cross-neutralizing potency after a single vaccination, highlighting the potential benefit of ZIKV vaccination in flavivirus-endemic areas.
Asymptomatic Zika infections can lead to severe birth defects and neurologic complications. The ZPIV vaccine candidate was developed by WRAIR based on the same inactivated flavivirus vaccine technology the Institute used to create its Japanese encephalitis vaccine, which was licensed in the U.S. in 2009. Three Phase 1 human clinical trials have shown ZPIV to be safe and well-tolerated in healthy adults and that it induced a robust immune response (Modjarrad et al., 2018). WRAIR’s Zika efforts are ongoing, overseen by the Institute’s Emerging Infectious Diseases Branch.
Vaccine candidates protect against Zika virus in rhesus monkeys
Researchers analyzed the antibody responses of a dengue-experienced volunteer who participated in a Phase 1 clinical trial of the WRAIR-developed Zika purified inactivated virus vaccine. They identified a potent cross-reactive antibody called MZ4 that demonstrated a potent ability to neutralize the Zika virus as well as the dengue virus serotype-2 strain. In addition, MZ4 protected against Zika and dengue in a mouse model of infection.
“Rapid-onset countermeasures are needed to protect military personnel, travelers and residents in areas where emerging infections such as Zika and dengue viruses are already widespread and expanding,” said Dr. Kayvon Modjarrad, who leads the U.S. Army Zika vaccine program, directs the Emerging Infectious Diseases Branch at WRAIR and is one of the lead authors on the paper. “These results demonstrate the potential for MZ4 to be part of the prevention toolbox for these diseases.”
The individual’s immune profile was compared to trial volunteers who had no previous exposure to dengue virus. While the volunteer with prior dengue exposure experienced a sharp increase in antibodies that neutralize Zika and dengue viruses, following just one dose of the ZPIV vaccine, the dengue-naïve trial participants required two vaccinations to reach a similar magnitude of Zika antibody responses. Additionally, no cross-reactive antibody response to dengue virus.
“These new findings indicate that an effective Zika vaccine could both boost dengue virus immune responses and generate potent Zika neutralizing antibodies that might have unique potential as a prevention tool in regions where both dengue and Zika are prevalent,” said Dr. Shelly Krebs, a B cell researcher at WRAIR and senior author of the paper.
Building on these findings, researchers used samples from another Phase 1 study of the ZPIV vaccine currently being conducted in Puerto Rico, where there is a higher risk of exposure to flaviviruses, a family of viruses that includes Zika, dengue, Japanese encephalitis, yellow fever and West Nile viruses. WRAIR researchers found that vaccination with ZPIV in Puerto Rican individuals with prior flavivirus-experience yielded similar cross-neutralizing potency after a single vaccination, highlighting the potential benefit of ZIKV vaccination in flavivirus-endemic areas.
Asymptomatic Zika infections can lead to severe birth defects and neurologic complications. The ZPIV vaccine candidate was developed by WRAIR based on the same inactivated flavivirus vaccine technology the Institute used to create its Japanese encephalitis vaccine, which was licensed in the U.S. in 2009. Three Phase 1 human clinical trials have shown ZPIV to be safe and well-tolerated in healthy adults and that it induced a robust immune response (Modjarrad et al., 2018). WRAIR’s Zika efforts are ongoing, overseen by the Institute’s Emerging Infectious Diseases Branch.
Explore further
More information: Potent Zika and dengue cross-neutralizing antibodies induced by Zika vaccination in a dengue-experienced donor, Nature Medicine (2020). DOI: 10.1038/s41591-019-0746-2 , https://nature.com/articles/s41591-019-0746-2
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