PFIZER AND BIONTECH PROVIDE UPDATE ON OMICRON VARIANT

Posted on by • Posted in Clinical Research, Coronavirus, Coronavirus Delta Variant, Coronavirus Mutation, Coronavirus Omicron Variant, Pandemic, Unvaccinated, Vaccination, Vaccine, Vaccine Booster, Vaccine Development, Vaccine Efficacy, Vaccine Safety, Vaccine Supply • Leave a comment

https://www.pfizer.com/news/press-release/press-release-detail/pfizer-and-biontech-provide-update-omicron-variant

Pfizer shot provides partial omicron shield, study finds | The Japan Times
  • Preliminary laboratory studies demonstrate that three doses of the Pfizer-BioNTech COVID-19 Vaccine neutralize the Omicron variant (B.1.1.529 lineage) while two doses show significantly reduced neutralization titers
  • Data indicate that a third dose of BNT162b2 increases the neutralizing antibody titers by 25-fold compared to two doses against the Omicron variant; titers after the booster dose are comparable to titers observed after two doses against the wild-type virus which are associated with high levels of protection
  • As 80% of epitopes in the spike protein recognized by CD8+ T cells are not affected by the mutations in the Omicron variant, two doses may still induce protection against severe disease
  • The companies continue to advance the development of a variant-specific vaccine for Omicron and expect to have it available by March in the event that an adaption is needed to further increase the level and duration of protection – with no change expected to the companies’ four billion dose capacity for 2022

NEW YORK & MAINZ, Germany–(BUSINESS WIRE)– Pfizer Inc. (NYSE: PFE) and BioNTech SE (Nasdaq: BNTX) today announced results from an initial laboratory study demonstrating that serum antibodies induced by the Pfizer-BioNTech COVID-19 Vaccine (BNT162b2) neutralize the SARS-CoV-2 Omicron variant after three doses. Sera obtained from vaccinees one month after receiving the booster vaccination (third dose of BNT162b2 vaccine) neutralized the Omicron variant to levels that are comparable to thoseobserved for the wild-type SARS-CoV-2 spike protein after two doses.

This press release features multimedia. View the full release here: https://www.businesswire.com/news/home/20211208005542/en/

Sera from individuals who received two doses of the current COVID-19 vaccine did exhibit, on average, more than a 25-fold reduction in neutralization titers against the Omicron variant compared to wild-type, indicating that two doses of BNT162b2 may not be sufficient to protect against infection with the Omicron variant. However, as the vast majority of epitopes targeted by vaccine-induced T cells are not affected by the mutations in Omicron, the companies believe that vaccinated individuals may still be protected against severe forms of the disease and are closely monitoring real world effectiveness against Omicron, globally.

A more robust protection may be achieved by a third dose as data from additional studies of the companies indicate that a booster with the current COVID-19 vaccine from Pfizer and BioNTech increases the antibody titers by 25-fold. According to the companies’ preliminary data, a third dose provides a similar level of neutralizing antibodies to Omicron as is observed after two doses against wild-type and other variants that emerged before Omicron. These antibody levels are associated with high efficacy against both the wild-type virus and these variants. A third dose also strongly increases CD8+ T cell levels against multiple spike protein epitopes which are considered to correlate with the protection against severe disease. Compared to the wild-type virus, the vast majority of these epitopes remain unchanged in the Omicron spike variant.

“Although two doses of the vaccine may still offer protection against severe disease caused by the Omicron strain, it’s clear from these preliminary data that protection is improved with a third dose of our vaccine,” said Albert Bourla, Chairman and Chief Executive Officer, Pfizer. “Ensuring as many people as possible are fully vaccinated with the first two dose series and a booster remains the best course of action to prevent the spread of COVID-19.”

“Our preliminary, first dataset indicate that a third dose could still offer a sufficient level of protection from disease of any severity caused by the Omicron variant,” said Ugur Sahin, M.D., CEO and Co-Founder of BioNTech. “Broad vaccination and booster campaigns around the world could help us to better protect people everywhere and to get through the winter season. We continue to work on an adapted vaccine which, we believe, will help to induce a high level of protection against Omicron-induced COVID-19 disease as well as a prolonged protection compared to the current vaccine.”

While these results are preliminary, the companies will continue to collect more laboratory data and evaluate real-world effectiveness to assess and confirm protection against Omicron and inform the most effective path forward. On November 25, the companies started to develop an Omicron-specific COVID-19 vaccine. The development will continue as planned in the event that a vaccine adaption is needed to increase the level and duration of protection against Omicron. First batches of the Omicron-based vaccine can be produced and are planned to be ready for deliveries within 100 days, pending regulatory approval. Pfizer and BioNTech have tested other variant-specific vaccines as well, which have produced very strong neutralization titers and a tolerable safety profile. Based on this experience the companies have high confidence that if needed they can deliver an Omicron-based vaccine in March 2022. The companies have also previously initiated clinical trials with variant-specific vaccines (Alpha, Beta, Delta & Alpha/Delta Mix) and data from these studies will be submitted to regulatory agencies around the world to help accelerate the process of adapting the vaccine and gaining regulatory authorization or approval of an Omicron-specific vaccine, if needed. The companies have previously announced that they expect to produce four billion doses of BNT162b2 in 2022, and this capacity is not expected to change if an adapted vaccine is required.

About the Pfizer-BioNTech Laboratory Studies

To evaluate the effectiveness of BNT162b2 against the Omicron variant, Pfizer and BioNTech immediately tested a panel of human immune sera obtained from the blood of individuals that received two or three 30-µg doses of the current Pfizer-BioNTech COVID-19 vaccine, using a pseudovirus neutralization test (pVNT). The sera were collected from subjects 3 weeks after receiving the second dose or one month after receiving the third dose of the Pfizer-BioNTech COVID-19 vaccine. Each serum was tested simultaneously for its neutralizing antibody titer against the wild-type SARS-Cov-2 spike protein, and the Omicron spike variant. The third dose significantly increased the neutralizing antibody titers against the Omicron strain spike by 25-fold. Neutralization against the Omicron variant after three doses of the Pfizer-BioNTech COVID-19 vaccine was comparable to the neutralization against the wild-type strain observed in sera from individuals who received two doses of the companies’ COVID-19 vaccine: The geometric mean titer (GMT) of neutralizing antibody against the Omicron variant measured in the samples was 154 (after three doses), compared to 398 against the Delta variant (after three doses) and 155 against the ancestral strain (after two doses). Data on the persistence of neutralizing titers over time after a booster dose of BNT162b2 against the Omicron variant will be collected.

The Pfizer-BioNTech COVID-19 vaccine, which is based on BioNTech’s proprietary mRNA technology, was developed by both BioNTech and Pfizer. BioNTech is the Marketing Authorization Holder in the United States, the European Union, the United Kingdom, Canada and other countries and the holder of emergency use authorizations or equivalents in the United States (jointly with Pfizer) and other countries. Submissions to pursue regulatory approvals in those countries where emergency use authorizations or equivalent were initially granted are planned.

Supreme Court hears 340B rate cut case

Posted on by • Posted in American Hospital Association (AHA), American Hospital Association v Becerra, Chevron Doctrine, Health Policy, Health System, Hospital, Hospital Industry, Medicare 340B Drug Discount Program, Pharmaceutical Industry, Supreme Court • Leave a comment

https://mailchi.mp/016621f2184b/the-weekly-gist-december-3-2021?e=d1e747d2d8

Earlier this week, the American Hospital Association (AHA) made its case before the US Supreme Court, in opposition to Medicare reimbursement cuts to hospitals that participate in the 340B Drug Pricing Program. The program allows hospitals that serve low-income patients to purchase outpatient drugs at a discount.

In the graphic above, we look at what’s at stake for hospitals in the case. Beginning in 2018, Medicare cut reimbursement for 340B-eligible drugs purchased by most hospitals by 28.5 percentage points, amounting to roughly $1.6B annually—which was a significant hit to hospitals’ 340B revenue. As we recently discussed, that revenue has become essential for many hospitals’ financial sustainability. However, the true impact on hospital bottom lines is more nuanced, as the savings from 340B rate cuts are being redistributed to all hospitals that participate in the Outpatient Prospective Payment System (OPPS), regardless of their 340B status, via a 3.2 percent payment bump for non-drug Part B services. While the cut negatively impacts those with large 340B programs—generally larger hospitals located in urban areas—the resulting redistribution actually provides a net benefit to about four in five hospitals.

Although 340B program revenues are at stake, the broader legal question before the Court centers on the level of authority federal agencies like the Centers for Medicare & Medicaid Services (CMS) have to create regulations to interpret ambiguous laws. (If the justices rule against CMS, it will overturn a key legal doctrine known as the Chevron Defense, which compels courts to defer to an agency’s interpretation of unclear statutes.)

A ruling isn’t expected until next spring, but regardless of the outcome, the 340B program faces other threats, chiefly from several lawsuits involving large pharmaceutical manufacturers’ moves to restrict discounted product sales to contract pharmacies. Undoubtedly, the ongoing scrutiny of the 340B program will continue to raise questions about whether there are better ways to subsidize the operations of hospitals serving low-income patients and ensure that underserved patients have access to lifesaving treatments.

Strategic misalignment at the heart of a governance issue

Posted on by • Posted in Consensus, Government, Health System, Hospital, Hospital Industry, Leadership Alignment, Leadership Assessment, Leadership Vision, Strategic Advantage, Strategic Alignment, Strategic Leadership • Leave a comment

https://mailchi.mp/016621f2184b/the-weekly-gist-december-3-2021?e=d1e747d2d8

When Innovation and Strategy Don't Align - TENZING Strategic

In our work with health systems, physician groups, and other organizations over the years, we’ve often been asked to facilitate board-level discussions about governance—resolving board conflicts, navigating difficult decisions, evaluating board composition.

A recent discussion again highlighted one of our main observations in working with boards: governance problems are often strategy problems in disguise. Working with a system that has grown through acquisition over the years, and whose board includes members from several of the “legacy” hospitals which had merged into the system over time, we were asked to help facilitate a dialogue about investment priorities across the component parts of the system.

At the root of the issue: each of the “representatives” of the subsidiary entities were pushing to have their own investment needs take precedence. On the face of it, that’s a governance problem: boards shouldn’t be constituent assemblies, with each member representing the interests of a sub-unit. Rather, they should act with one purpose: to advance the interests of the whole.

But that misalignment turned out to be a symptom of a larger problem: there was no consensus at the board level about what the strategic direction of the combined system should be, and what role each component part played in that direction.

That’s a strategy problem, masquerading as a governance issue. Identifying the strategic issue allowed the board to reframe the dialogue around vision, which then unblocked the subsequent decisions about investments. Good strategy and good governance go hand in hand.

The omicron variant: The ‘good,’ ‘bad,’ and ‘ugly’ scenarios

Posted on by • Posted in Clinical Research, Coronavirus, Coronavirus Delta Variant, Coronavirus Mutation, Coronavirus Omicron Variant, Unvaccinated, Vaccination, Vaccine, Vaccine Booster, Vaccine Efficacy, Vaccine Safety, Vaccine Supply • Leave a comment

https://www.advisory.com/daily-briefing/2021/11/30/omicron-future

Will there be a winter lockdown? Experts set out three scenarios - the good, the bad and the ugly

Déjà vu.

That’s what we felt when news broke about a new coronavirus variant, named omicron, being designated as a “variant of concern.” It’s been nearly two years since Covid-19 was declared a global pandemic, and we’re yet again wondering what the future holds.

Once again, there are no clear answers. But we do know enough to begin mapping out the space of possibilities.

We know enough to ask, as we have at past moments in the pandemic: What are the (relatively) “good,” “bad,” and “ugly” scenarios? 

Full disclosure: Even in the day it took us to draft this post, we’ve had to rethink our beliefs in light of emerging information. Still, even if these predictions are shaky, we believe there’s value in reflecting on the futures that could arise—and how health care stakeholders can prepare for each one.

The (relatively) ‘good’ scenario: Our existing vaccines and treatments still work, and omicron doesn’t cause worse disease.

It would be misguided to label any outcome as truly “good” in a pandemic that has already killed more than 775,000 Americans and more than 5 million people worldwide.

Still, some possible futures are clearly better than others—and the best-case scenarios are those in which the omicron variant doesn’t fundamentally change the course of the pandemic.

America has already given 74% of people aged 5+ at least one vaccine dose. If those vaccines are as effective against omicron as other variants, that will be a promising sign for the pandemic’s future.

It’s even possible that omicron’s emergence could drive increased vaccine and booster uptake, as happened in the initial weeks of the delta surge. It could even advance efforts to vaccinate the world, a task that President Biden deemed a “moral obligation” in his early remarks on the omicron variant.

So how likely are current vaccines to work against the omicron variant? One reason for optimism is that most early cases and hospitalizations in South Africa appear to have occurred in unvaccinated individuals. Another is that vaccines have worked well against all past variants, including delta. Still, experts caution that omicron carries more mutations than past variants, and many of those mutations exist in areas associated in lab experiments with immune escape. In the coming weeks, we’ll have more data on whether the vaccines protect against the variant.

Another “good” possibility would that omicron doesn’t make people as sick as other variants (or, put more formally, that it’s not especially virulent). Here, too, there’s reason for optimism. Early reports out of South Africa indicate that most infected individuals have suffered only minor or asymptomatic illnesses.

But there’s also reason for caution: Because the variant has emerged so recently, it’s possible that most cases simply haven’t had time to progress to hospitalization and death. According to WHO, there’s simply no evidence to suggest that omicron’s symptoms are any better or worse than those caused by past variants.

On the whole, we think a relatively good scenario remains plausible, especially in highly vaccinated regions. Additionally, our current preparedness measures—like increased testing and vaccinations, as well as even renewed calls from Dr. Francis Collins from the NIH for mask wearing indoors—may help us get ahead of omicron’s spread, at least in the U.S. But there’s also a risk that things will turn worse.

The ‘bad’ scenario: Omicron is highly transmissible and slightly more virulent than previous variants, but existing vaccines and treatments still work well.

In the “bad” scenario, the omicron variant’s course could look very similar to that taken by the delta variant in the summer. It could rapidly spread throughout the nation and world, with the most severe impacts on unvaccinated populations.

Transmissibility could be a key factor in this scenario, and data on the variant’s basic reproduction ratio (R0) a metric used to describe the contagiousness or transmissibility of infectious agents, will help us further understand potential impact. The original coronavirus had a R0 of 2.79, and the delta variant had a R0 of 5.08. If the omicron variant’s R0 exceeds this number (and is more virulent), we may find ourselves in a “bad” scenario. Experts have speculated that omicron is likely highly transmissible since it carries mutations found on the very contagious delta variant, as well as other mutations hypothesized to increase transmissibility. The variant’s apparently rapid rise in South Africa also suggests it spreads easily, although experts warn we don’t yet know for sure.

If omicron turns out to be the most transmissible variant yet, we should expect another wave of cases among the unvaccinated, likely accompanied by an increase in breakthrough infections. However, so long as our vaccines still are effective, most breakthrough infections will be mild, as was the case during the delta surge.

Even in this “bad” scenario, we’re still much better off than in past coronavirus waves. In just the last several weeks, we’ve seen the emergence of new, promising treatments—notably, oral antivirals that reduce the risk of hospitalization and severe illness. Pfizer’s antiviral, Paxlovid, was shown to provide an 89% risk reduction in outpatients. Merck’s antiviral, molnupiravir, was recently shown to reduce the risk of hospitalization and death from Covid-19 by 30%.

Because of the way these treatments work in the body, experts feel confident they’ll remain effective against the omicron variant. It’s possible that, at least at first, they could be reserved for unvaccinated people or high-risk groups or sent to areas with the greatest prevalence of the variant. It’s likely that FDA will discuss these possibilities as it reviews these drugs’ applications for emergency use authorization. It will also be essential that we can overcome some of the big obstacles for anti-viral treatments, such as access, rapid testing, and sufficient tracking.

Still, while post-exposure drugs will play an important role in a “bad” scenario, the key to preventing a truly “ugly” outcome will be vaccines. The World Health Organization and the Biden administration both echoed this message, recently urging people to get vaccinated and boosted to prevent further spread. Additionally, CDC just strengthened its booster recommendations, saying all eligible adults “should” get boosted (where previous guidance said they “may” get boosted) and Pfizer announced it is seeking approval of boosters for people ages 16 and 17.

The sooner vaccines are distributed throughout America and the world, the better the outcome will be—at least so long as the vaccines themselves remain effective.

The ‘ugly’ scenario: Vaccines falter, and omicron’s virulence is dangerously high.

The biggest question, then, is: What happens if our current vaccines falter?

Here’s where we want to be cautious. Most experts say omicron is extremely unlikely to fully evade existing vaccines. Scott Gottlieb, former FDA commissioner, recently said that “… if you talk to people in vaccine circles… they have a pretty good degree of confidence that a booster vaccine so three full doses of vaccine is going to be fairly protective against this new variant.” It would be irresponsible, and unhelpful, for us to speculate—in absence of any evidence, and against scientists’ best predictions—that vaccines could simply stop working.

But it’s possible that omicron will show a degree of immune escape.

If so, then many people who are vaccinated could fall ill. They in turn could pass the virus to others. And if omicron proves to be as virulent as or worse than past variants, many of those infected—especially those who are unvaccinated—will suffer and die.

This would render the next 100 days truly “ugly,” as manufacturers race to develop new vaccines and boosters against the new variant, and an already exhausted health care system copes with yet another devastating wave of cases.

In this scenario, health care leaders, policymakers, and public health officials will need to re-evaluate preventive strategies. We could once again see draconian measures such as lockdowns and sustained capacity mandates. However, President Biden recently announced that the U.S. will not resort to lockdowns or shutdowns as a result of omicron, making this possibility unlikely.

Even this scary scenario wouldn’t quite bring us back to March 2020. We know dramatically more than we did then about how to detect, contain, and treat Covid-19, and manufacturers stand ready to adapt their vaccines with all due haste.

But this scenario would be horrific, and the next few months would feel all too much like déjà vu.

Parting thoughts

When we’ve written these predictions about the pandemic in the past, we struggled to see how our individual actions could meaningfully inflect our trajectory toward a good, bad, or ugly outcome.

But whether one or none of these scenarios play out, it is important to step back and consider how we can rely on lessons we’ve learned over the past two years. Lessons such as encouraging vaccine uptake by going into the community, combatting structural inequities by acknowledging and acting, helping out vulnerable countries around the world, supporting the health care workforce, and much more.

If you are feeling overwhelmed after reading through these various scenarios, stuck in the treacherous mental waters of the unknown, you are not alone. It is okay to acknowledge the confusion of constantly emerging data as we learn how to proceed. But this is also true: these unknowns will not be the end of us. Somehow, amid the chaos of constant pandemic updates and new death tolls, we continue to move forward as a collective—doing our best to stay prepared, protected, and proactive.

And for us, that is a reason for hope.

Omicron: What we know (and still don’t) about the new variant

Posted on by • Posted in Clinical Research, Coronavirus, Coronavirus Delta Variant, Coronavirus Mutation, Coronavirus Omicron Variant, Vaccination, Vaccine, Vaccine Booster, Vaccine Efficacy, Vaccine Safety, Vaccine Supply • Leave a comment
https://www.advisory.com/daily-briefing/2021/12/02/omicron-update?utm_source=public_db&utm_medium=email&utm_campaign=2021dec02&utm_content=public_headline_public_x_x_x_x&elq_cid=4778863&x_id=
Michigan braces for omicron as COVID-19 hospitalizations climb

The new omicron variant is “more of a Frankenstein” than previous virus coronavirus variants, according to one virologist, and vaccine experts are at odds over how well current vaccines will provide protection against it.

A ‘Frankenstein’ variant

According to Alex Sigal, a virologist heading a team of researchers at the Africa Health Research Institute, the new variant is “probably the most mutated virus we’d ever seen.” However, Sigal added that he believes existing Covid-19 vaccines will continue to protect people against severe disease and hospitalization.

Similarly, Ugur Sahin, BioNTech co-founder, said that the Pfizer-BioNTech vaccine not only creates antibodies that prevent infection from occurring, but also creates T lymphocytes that attack cells after the body has been infected. Sahin argued that, even if omicron can evade antibodies, it would likely be vulnerable to T lymphocytes.

“Our message is: Don’t freak out, the plan remains the same: Speed up the administration of a third booster shot,” Sahin said.

Luke O’Neill, an immunologist and chair of biochemistry at Trinity College Dublin, said Sahin’s assumption makes sense from an immunological perspective. “There is optimism that the T-cells will hold the line—they are very good at stopping severe disease,” O’Neill said.

However, Stanley Plotkin, a scientist who has developed many vaccines, said Sahin’s assumptions were “gratuitous and without any proof.” Plotkin said so far there’s little evidence to suggest T-cells could fully protect against severe symptoms if a virus evades antibodies.

Further, Stéphane Bancel, CEO of Moderna, said, “There is no world, I think, where [the effectiveness] is the same level … we had with [the] Delta [variant] … I think it’s going to be a material drop. I just don’t know how much because we need to wait for the data. But all the scientists I’ve talked to … are like, ‘This is not going to be good.'”

However, former FDA commissioner Scott Gottlieb on Monday said, “There’s a reasonable degree of confidence in vaccine circles that [with] at least three doses … the patient is going to have fairly good protection against this variant.”

Angelique Coetzee, national chair of the South African Medical Association, said that so far, vaccinated patients who have tested positive for omicron “have no complication.” She noted that the nation’s hospitals were not overwhelmed by omicron patients, and most of those hospitalized were not fully vaccinated. Additionally, most patients she had seen did not lose their sense of taste and smell, and had only a slight cough, the New York Times reports.

“I have seen vaccinated people and not really very sick,” Coetzee said. “That might change going forward, as we say, this is early days. And this is maybe what makes us hopeful.”

Could omicron ‘outcompete’ delta?

Separately, Adrian Puren, acting executive director of South Africa’s National Institute for Communicable Diseases, said he believes omicron could become more pervasive than the delta variant. “We thought what will outcompete delta? That has always been the question, in terms of transmissibility at least … perhaps this particular variant is the variant,” Puren said.

William Schaffner, a professor of preventive medicine at Vanderbilt University School of Medicine, said that while nothing is certain yet, “it looks as though [omicron] will be as infectious as delta.”

As for how long it will take to answer questions about omicron, including its transmissibility and virulence, Tara Smith, an epidemiologist at Kent State University, said at minimum “it will take a month to get some preliminary data, and quite possibly longer to really know the fuller picture. We also won’t know about real-world experience in vaccine breakthroughs until that time.”