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Wednesday, September 1, 2021

Two-thirds say COVID-19 situation is getting worse: Gallup

 Two-thirds of Americans say the coronavirus situation is getting worse as delta variant cases have overrun hospitals across the country, a new Gallup poll shows.

The poll found 68 percent of adults say the coronavirus situation is worsening, a significant reversal from June, when 89 percent of adults said they thought the coronavirus situation was getting better.

Currently, only 15 percent of respondents said they believe the coronavirus is getting better.

This is the third-lowest point for public confidence during the pandemic, after July 2020 and November.

There is a slight partisan divide in the results: 84 percent of Democrats believe the coronavirus situation is worsening, while only 51 percent of Republicans .

The increased fear of a worsening pandemic situation comes as vaccinations have slowed in the U.S. while the delta variant has caused a spike in infections nationwide.

Many states are seeing a strain on their hospitals, and some governors have begun calling in the National Guard and the Federal Emergency Management Agency for backup.

Currently, 39 percent of Americans are somewhat or very worried about catching the coronavirus, with 24 percent “completely” or “mostly” staying in their homes.

Masking is still the most popular mitigation, with 69 percent of individuals wearing a mask outside their home. 

The spike in cases caused the Centers for Disease Control and Prevention to reimplement recommendations for fully vaccinated individuals to wear masks indoors in areas with high COVID-19 transmission.

https://thehill.com/policy/healthcare/570324-two-thirds-say-covid-19-situation-is-getting-worse-gallup

California hits 80% level for covid vaccinations

 California on Tuesday surpassed the 80 percent threshold for residents ages 12 and older who have received at least one dose of the coronavirus vaccine, with officials urging those who have not yet gotten the shot to do so quickly to prevent further surges in cases and hospitalizations.

Gov. Gavin Newsom (D) announced the milestone in a press release, noting that California has “put more shots in arms than any other state.”

“We’ve made incredible progress vaccinating our population in a remarkably short amount of time, and our work continues to close the gap in our most impacted communities,” he added in a statement.

Newsom went on to argue that “getting vaccinated is the key to protecting against COVID-19 and the faster-spreading Delta variant.” 

“It’s how we end this thing,” he said. 

Newsom, who is facing a recall election later this month, has joined other California leaders to push for increased vaccinations by citing the Food and Drug Administration’s full approval of the Pfizer-BioNTech vaccine for Americans ages 16 and older.

The Pfizer vaccine is the first COVID-19 vaccine in the U.S. to move past an emergency use authorization. Those as young as 12 can also get the vaccine under the emergency authorization.

As of Tuesday, nearly 69 percent of California’s total population had received at least one COVID-19 shot, with about 56 percent fully vaccinated, according to the Centers for Disease Control and Prevention

Newsom also on Tuesday released his latest “On the Record” ethnic media column, in which he noted that “many of our most vulnerable communities where we are seeing low vaccination rates are targets of disinformation campaigns, which continue to put lives at risk, including our youngest children who are not yet eligible to receive the COVID-19 vaccine.” 

“Working with ethnic media, faith-based and community-based organizations, and many unique partners who are trusted messengers has been crucial to dispelling some of the most prevalent myths out there,” he added. 

“It’s time to fully embrace the facts that prove vaccines work, are safe, and are free – regardless of immigration status,” Newsom said. 

Last month, the governor announced that all state employees and health care workers would be required to either provide proof of vaccination or submit to weekly COVID-19 testing. 

California earlier this month also said it would be imposing a similar vaccination requirement for teachers and staff at public schools across the state, with Newsom calling it “a sustainable way of keeping schools open.” 

The state has also required all teachers and students to wear masks in schools, an issue which has resulted in legal battles in places like Texas and Florida, which have both imposed bans on school mask mandates.

https://thehill.com/policy/healthcare/570357-california-hits-80-percent-threshold-for-vaccinations

WHO investigating new COVID-19 variant named Mu

 The World Health Organization said it is monitoring another new COVID-19 variant with mutations that the agency fears could make it resistant to vaccines.

The Mu variant, also known as B.1.621, was added as a “variant of interest” to the organization’s watch list Monday.

“The Mu variant has a constellation of mutations that indicate potential properties of immune escape,” the bulletin said.

Preliminary data indicated that it may evade vaccines in a way similar to the Beta variant, but experts said more research on the strain is necessary.

Since first emerging in Colombia in January 2021, the Mu variant has popped up in at least 39 countries.

“Although the global prevalence of the Mu variant among sequenced cases has declined and is currently below 0.1%, the prevalence in Colombia (39%) and Ecuador

(13%) has consistently increased,” the agency said, though it added the uptick could be due to increased genetic sequencing.

The concerns over the new strain come as the highly contagious Delta variant has driven surges in cases across the globe.

https://nypost.com/2021/09/01/who-investigating-new-covid-19-variant-named-mu/

Lack of Vaccine Mandate a Competitive Edge in Hospital Staffing Wars

 In the rural northeastern corner of Missouri, Scotland County Hospital has been so low on staff that it sometimes had to turn away patients amid a surge in covid-19 cases.

The national covid staffing crunch means CEO Dr. Randy Tobler has hired more travel nurses to fill the gaps. And the prices are steep — what he called "crazy" rates of $200 an hour or more, which Tobler said his small rural hospital cannot afford.

A little over 60% of his staff is fully vaccinated. Even as covid cases rise, though, a vaccine mandate is out of the question.

"If that becomes our differential advantage, we probably won't have one until we're forced to have one," Tobler said. "Maybe that's the thing that will keep nurses here."

As of Thursday, about 39% of U.S. hospitals had announced vaccine mandates, said Colin Milligan, a spokesperson for the American Hospital Association. Across Missouri and the nation, hospitals are weighing more than patient and caregiver health in deciding whether to mandate covid vaccines for staffers.

The market for health care labor, strained by more than a year and a half of coping with the pandemic, continues to be pinched. While urban hospitals with deeper pockets for shoring up staff have implemented vaccine mandates, and may even use them as a selling point to recruit staffers and patients, their rural and regional counterparts are left with hard choices as cases surge again.

"Obviously, it's going to be a real challenge for these small, rural hospitals to mandate a vaccine when they're already facing such significant workforce shortages," said Alan Morgan, head of the National Rural Health Association.

Without vaccine mandates, this could lead to a desperate cycle: Areas with fewer vaccinated residents likely have fewer vaccinated hospital workers, too, making them more likely to be hard hit by the delta variant sweeping America. In the short term, mandates might drive away some workers. But the surge could also squeeze the hospital workforce further as patients flood in and staffers take sick days.

Rural covid mortality rates were almost 70% higher on average than urban ones for the week ending Aug. 15, according to the Rural Policy Research Institute.

Despite the scientific knowledge that covid vaccinations sharply lower the risk of infection, hospitalization and death, the lack of a vaccine mandate can serve as a hospital recruiting tool. In Nebraska, the state veterans affairs' agency prominently displays the lack of a vaccine requirement for nurses on its job site, The Associated Press reported.

It all comes back to workforce shortages, especially in more vaccine-hesitant communities, said Jacy Warrell, executive director of the Rural Health Association of Tennessee. She pointed out that some regional health care systems don't qualify for staffing assistance from the National Guard as they have fewer than 200 beds. A potential vaccine mandate further endangers their staffing numbers, she said.

"They're going to have to think twice about it," Warrell said. "They're going to have to weigh the risk and benefit there."

The mandates are having ripple effects throughout the health care industry. The federal government has mandated that all nursing homes require covid vaccinations or risk losing Medicare and Medicaid reimbursements, and industry groups have warned that workers may jump to other health care settings. Meanwhile, Montana has banned vaccine mandates altogether, and the Montana Hospital Association has gotten one call from a health care worker interested in working in the state because of it, said spokesperson Katy Peterson.

It's not just nurses at stake with vaccine mandates. Respiratory techs, nursing assistants, food service employees, billing staff and other health care workers are already in short supply. According to the latest KFF/The Washington Post Frontline Health Care Workers Survey, released in April, at least one-third of health care workers who assist with patient care and administrative tasks have considered leaving the workforce.

The combination of burnout and added stress of people leaving their jobs has worn down the health care workers the public often forgets about, said interventional radiology tech Joseph Brown, who works at Sutter Roseville Medical Center outside Sacramento, California.

This has a domino effect, Brown said: More of his co-workers are going on stress and medical leave as their numbers dwindle and while hospitals run out of beds. He said nurses' aides already doing backbreaking work are suddenly forced to care for more patients.

"Explain to me how you get 15 people up to a toilet, do the vitals, change the beds, provide the care you're supposed to provide for 15 people in an eight-hour shift and not injure yourself," he said.

In Missouri, Tobler said his wife, Heliene, is training to be a volunteer certified medical assistant to help fill the gap in the hospital's rural health clinic.

Tobler is waiting to see if the larger St. Louis hospitals lose staff in the coming weeks as their vaccine mandates go into effect, and what impact that could have throughout the state.

In the hard-hit southwestern corner of Missouri, CoxHealth president and CEO Steve Edwards said his health system headquartered in Springfield is upping its minimum wage to $15.25 an hour to compete for workers.

While the estimated $25 million price tag of such a salary boost will take away about half the hospital system's bottom line, Edwards said, the investment is necessary to keep up with the competitive labor market and cushion the blow of the potential loss of staffers to the hospital's upcoming Oct. 15 vaccine mandate.

"We're asking people to take bedpans and work all night and do really difficult work and maybe put themselves in harm's way," he said. "It seems like a much harder job than some of these 9-to-5 jobs in an Amazon distribution center."

Two of his employees died from covid. In July alone, Edwards said 500 staffers were out, predominantly due to the virus. The vaccine mandate could keep that from happening, Edwards said.

"You may have the finest neurosurgeon, but if you don't have a registration person everything stops," he said. "We're all interdependent on each other."

But California's Brown, who is vaccinated, said he worries about his colleagues who may lose their jobs because they are unwilling to comply with vaccine mandates.

California has mandated that health care workers complete their covid vaccination shots by the end of September. The state is already seeing traveling nurses turn down assignments there because they do not want to be vaccinated, CalMatters reported.

Since the mandate applies statewide, workers cannot go work at another hospital without vaccine requirements nearby. Brown is frustrated that hospital administrators and lawmakers, who have "zero covid exposure," are the ones making those decisions.

"Hospitals across the country posted signs that said 'Health care heroes work here.' Where is the reward for our heroes?" he asked. "Right now, the hospitals are telling us the reward for the heroes: 'If you don't get the vaccine, you're fired.'"

https://www.medscape.com/viewarticle/957868

US FDA approval tracker: August

 Fibrogen’s roxadustat received an expected FDA knockback last month after a negative panel in July. The FDA requested another study, but in the EU the outcome was wildly different, and full approval was granted eight days after the US disappointment. Two other US complete response letters were handed out, one for Spectrum’s Rolontis, owing to manufacturing issues, and the other for Sesen’s Vicineum. The regulators requested a whole new confirmatory trial for Sesen’s bladder cancer project, pushing a resubmission out to 2023. However, it was not all bad news last month as several approval decisions pegged for September came early. The most notable involved Ascendis’s growth hormone Skytofa, and Bristol Myers Squibb’s Opdivo for adjuvant treatment of high-risk urothelial carcinoma; the latter had been filed for muscle-invasive disease, based on the Checkmate-274 study, but the approved label makes no mention of this stipulation (Go or no go? A first for Nefecon, August 27, 2021).

Notable first-time US approval decisions in August
ProjectCompanyIndication(s)2026e sales by indication ($m)Outcome
ComirnatyPfizer/BiontechPrevention of Covid-19 (aged 16 and older)2,819Full approval
(still under EUA for ages 12-15)
Evrenzo (roxadustat)Fibrogen/Astrazeneca/
Astellas
Anaemia in patients with chronic kidney disease on/not on dialysis1,666CRL
(additional trial needed)
Skytrofa (Transcon hGH/
lonapegsomatropin)
AscendisPaediatric growth hormone deficiency1,371Approved (~1mth early)
AXS-05AxsomeMajor depressive disorder1,277*Delayed (no new date given)
Welireg
(MK-6482/belzutifan)
Merck & CoVon Hippel-Lindau disease-associated renal cancer386Approved (~1mth early)
Nexviazyme
(avalglucosidase alfa)
SanofiPompe disease366Approved
Korsuva injectionCara/ViforPruritis in haemodialysis patients358Approved
RolontisSpectrumNeutropenia  in patients receiving myelosuppressive anti-cancer drugs330CRL
(manufacturing, reinspection needed)
VicineumSesen BioHigh risk BCG-unresponsive non-muscle invasive bladder cancer292CRL (CMC & new trial)
TicoVacPfizerTick-borne encephalitis218Approved
Topiramate oral solutionEtonTonic-clonic seizures, partial-onset seizures, and as preventative treatment of migraine-Extended to Nov 6
EpsolaySol-GelPapulopustular rosacea-No decision yet
 *SBI not split out by depression type. Source: Evaluate Pharma & company releases.

 

Supplementary and other notable approval decisions in August
ProductCompanyIndication (clinical trial)Outcome
JemperliGSK/AnaptysbioAdult patients with MMR-deficient recurrent or advanced solid tumours (Garnet)Approved (accelerated)
JardianceLilly/BoehringerHeart failure with reduced ejection fraction (Emperor-Reduced)Approved (~3wks early)
Opdivo Bristol Myers SquibbAdjuvant treatment for patients with high-risk urothelial carcinoma (Checkmate-274)Approved (2wks early)
XareltoJ&JPeripheral artery disease patients post lower-extremity revascularisation (Voyager PAD)Approved
TibsovoServierPreviously treated, locally advanced or metastatic cholangiocarcinoma with an IDH1 mutation (ClarIDHy)Approved
XywavJazzAdult patients with idiopathic hypersomnia (NCT03533114)Approved
Keytruda + LenvimaMerck/Eisai1L renal cell carcinoma (Clear/Keynote-581/Study 307)Approved
Source: Evaluate Pharma & company releases.

 

Voluntarily withdrawn accelerated approvals
ProductCompanyWithdrawn indication (clinical trials)
IstodaxBristol Myers Squibb2L peripheral T-cell lymphoma
Tecentriq (+ Abraxane)RochePD-L1-positive, 1L triple-negative breast cancer (Impassion-130Impassion-131)
Source: company releases.

https://www.evaluate.com/vantage/articles/news/snippets/us-fda-approval-tracker-august-0

'COVID-19 booster shots are more complicated than they appear'

 Not everyone agrees that COVID-19 booster shots are necessary for all vaccinated Americans, and that discord may slow down plans to roll out extra doses of the mRNA vaccines later this month and change who is eligible for them.

Dr. Sara Oliver, who leads the COVID-19 vaccines work group and is a Centers for Disease Control and Prevention official, on Monday said the “priority for booster dose policy should be the prevention of severe disease in at risk-population,” citing nursing-home residents and front line health care workers as examples. 

The presentation was part of a meeting of the CDC’s Advisory Committee on Immunization Practices, a group of independent public-health experts who make recommendations about vaccines to the CDC following authorization or approval from the Food and Drug Administration. 

White House officials, including President Joe Biden, last month said that Americans who were vaccinated with BioNTech SE BNTX, +0.83% and Pfizer Inc. PFE, -1.07% or Moderna Inc.’s MRNA, +2.22% COVID-19 vaccines can get a booster dose starting Sept. 20, as long it has been eight months since someone has been fully vaccinated, the FDA authorizes or approves the booster, and the CDC gives its blessing. They said the first boosters will likely go to groups of people who are at higher risk of severe disease. 

(The White House also said that people who got Johnson & Johnson’s JNJ, -0.53% single-shot vaccine will likely need a second dose, though no further details have been shared at this time.)

That said, U.S. regulators have yet to OK a booster dose for the general public, and that has become a point of contention for some public-health experts.

The Biden administration’s announcement “led everyone—it led physicians, it led the public—to believe that they had access to information about these vaccines and the need for boosters that had not yet been publicly released,” Dr. Sandra Adamson Fryhofer, an adjunct associate professor of medicine at Emory University School of Medicine, said Monday. “To me, that opened the door to a lot of confusion.”

Fryhofer serves as a liaison to ACIP for the American Medical Association.

Federal health officials have said they are concerned that the vaccines will soon be less effective at protecting people against severe disease, hospitalization, and death, and that is their rationale for booster shots.

When asked about the ACIP’s booster discussion on Tuesday, CDC director Dr. Rochelle Walensky said the committee had only evaluated U.S. data so far.

“It is our own data as well as international data that has led us to be concerned that the waning we’re seeing for infection will soon lead to waning that we would see for hospitalization and severe disease and death,” she said.

However, infectious-disease physicians previously told MarketWatch that clinical decisions for COVID-19 booster shots should be based on data that’s available, not what’s projected to happen. 

What’s changed in the COVID-19 booster discussion

The national discourse around boosters has intensified over the last two months, driven by public promotion from Pfizer and Moderna, the Biden administration’s sudden support, and widespread utilization of extra doses in Israel, which is being closely watched by scientists to see how virus behaves in the highly vaccinated country. 

At the same time, cases have steadily increased in the U.S. since early July, as immunity has waned over time and the rapid spread of the more infectious delta variant has led to an increase in infections among the vaccinated and the unvaccinated. 

This was reiterated by Oliver at Monday’s meeting.

“All [COVID-19] vaccines remain effective in preventing hospitalization and severe disease, but they may be less effective in preventing infection or mild illness recently,” she said. “These reasons for lower effectiveness likely include both waning over time and the delta variant.”

However, most of the soaring number of hospitalizations and deaths we are seeing right now are occurring in unvaccinated Americans. 

“The data to date doesn’t show a remarkable reduction in the effectiveness of vaccines in terms of preventing hospitalizations and deaths,” Dr. Beth Bell, a clinical professor at the University of Washington’s School of Public Health and an ACIP member, said Monday. “The most important thing that we can do with respect to vaccines is to continue to work as hard as we possibly can to encourage more people to get the primary series.”

What exactly is a COVID-19 booster shot?

This is where things get complicated.

The CDC does not refer to extra doses for the immunocompromised as a booster shot. Instead, it is considered a third—or extra—dose because many of those people never mounted an immune response at all to initial vaccination, according to Oliver. (The only Americans who are currently eligible for an extra dose of the BioNTech/Pfizer or Moderna shots are some teens and adults with compromised immune systems, an authorization that was granted in August.)

The agency defines a booster dose as one that “boosts” immunity from a vaccine’s “primary series” that has waned over time.

There are also different kinds of boosters. A homologous booster uses the same vaccine, while a heterologous booster uses a different vaccine for the booster than what was used in the primary series.

Several “mix-and-match” clinical trials are already under way around the world, including one conducted by the National Institutes of Health that is testing a Moderna booster in people who received any of the three authorized or approved COVID-19 vaccines. 

In addition, drug makers are testing different doses of the vaccines in booster trials.

There is one more one idea to consider: perhaps the two-dose COVID-19 vaccines will actually become three-dose vaccines. (Dr. Paul Offit, director of the Vaccine Education Center at Children’s Hospital of Philadelphia, told me in August that this seems to be the White House’s plan. His view is that officials there are saying, “‘Let’s not wait for an erosion against severe illness. We’ll just offer a booster now, with the assumption being with that this will be a three-dose vaccine.'”)

Other vaccines including the human papillomavirus (HPV) and hepatitis B shots require three doses, spaced out over a year or so. For example, the third dose of the hepatitis B vaccine can be administered up to 18 months after the first dose.

“In a pandemic setting, it can be important to achieve high protection early with a second dose given at a shorter interval, however it may mean that a later dose for this boost effect is needed as well,” Oliver said. “This doesn’t necessarily mean that an annual booster dose would be needed.”

What comes next

BioNTech and Pfizer said last week that they had submitted data for a Comirnaty booster shot to the FDA. That data examined antibody levels in adults who got a third dose between four and eight months after initial vaccination.

Moderna and J&J have each said that booster doses can increase antibody levels among people immunized with their shots, though neither company has submitted that data to U.S. regulators at this time. 

The ACIP is expected to meet again in mid-September or if and when the FDA authorizes or approves a third dose of one of the vaccines, to then discuss how COVID-19 booster shots should be administered to the public. Monday’s meeting focused on setting out a framework for booster shots in the U.S. BioNTech/Pfizer, J&J, and Moderna will be asked to present clinical data for booster doses at coming meetings. 

“We read this meeting timing and the additional dose (‘booster’) discussion as an indication that uptick in third doses may not come as rapidly as investors have been expecting,” SVB Leerink analyst Daina Graybosch told investors on Tuesday. 

Jefferies analysts took a much more narrow view of the meeting, telling investors that they think the committee is leaning toward only recommending booster doses for high-risk populations like health care workers and the elderly. 

“The ACIP still appears to be hesitant on whether [additional] doses are needed despite waning antibodies and increasing infections,” they wrote. 

https://www.marketwatch.com/story/the-debate-over-covid-19-booster-shots-picks-up-steam-will-they-be-limited-to-certain-high-risk-americans-11630503813

Mesoblast's Novartis-partnered COVID-19 cell therapy hits a wall as FDA requests new trial

 Mesoblast has been put on blast by the FDA yet again after the agency requested another trial for its failed, Novartis-backed COVID-19 respiratory treatment.

The Australian cell therapy biotech will have to conduct another study of remestemcel-L to have a shot at an emergency use authorization from the FDA. It's another blow to Novartis, which doled out $50 million upfront and more than $1 billion in biobucks for a global license to the drug for acute respiratory distress syndrome (ARDS).

The treatment failed last December in a phase 3 study in 222 ventilator-dependent COVID-19 patients with moderate to severe ARDS and was halted early for showing no signs of reducing death in patients over the age of 65. Remestemcel-L showed a 48% reduction in death for patients under 65 years old after 90 days.

That trial flop caused Mesoblast to lose more than a third of its value on the Australian Securities Exchange last December. Tuesday's news didn't help either, with the shares dipping 5.71% as the markets opened Wednesday to $1.57 apiece.

If Mesoblast pulls off the requested study and gets some positive data, the biotech thinks the information combined with the earlier study "might be sufficient to support an EUA," according to a statement.

Potency assays must be established and agreed upon before Mesoblast can move forward with a trial, the FDA told the biotech. Mesoblast can also cross-reference manufacturing information in its biologics license application for the drug's indication in pediatric patients with steroid-refractory acute graft-versus-host disease (SR-aGvHD).

The FDA turned down Mesoblast's request for approval of remestemcel-L in SR-aGvHD last fall. The biotech said discussions are ongoing with the agency about the next steps for that disease.

The biotech may resubmit the SR-aGvHD application with a six-month review and will meet with the FDA's Office of Tissue and Advanced Therapies in the fourth quarter of this year to address the potency assays and outstanding questions around chemistry, manufacturing and controls.

Mesoblast is also hoping its other main asset, precursor cell therapy rexlemestrocel-L, will get somewhere after a mixed bag of results in a pair of phase 3 trials in patients with advanced chronic heart failure and chronic lower back pain due to degenerative disc disease. Mesoblast anticipates receiving feedback from the FDA this month on the regulatory pathway for those two indications.

https://www.fiercebiotech.com/biotech/mesoblast-craters-again-as-fda-requests-another-trial-failed-covid-19-respiratory-treatment