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Tuesday, January 12, 2021

'Sending National Guard to Washington could slow U.S. vaccine handout'

  The need to divert National Guard troops to Washington to provide security for next week’s inauguration of President-elect Joe Biden could hinder the distribution of coronavirus vaccines in various U.S. states, a Democratic lawmaker said.

Washington is reeling from the Jan. 6 attack on the U.S. Capitol by supporters of President Donald Trump and authorities are working to head off possible civil unrest during Biden’s Jan. 20 swearing-in at the Capitol.

As many as 15,000 National Guard troops have been authorized to be sent to Washington.

Democratic Representative Tim Ryan, who chairs a House committee that oversees the U.S. Capitol Police and security around the Capitol, said that National Guard troops could also be dispatched to several state capitals amid reports that Trump supporters will be staging protests around the nation next week.

Ryan said he spoke with National Guard officials on Monday and was told that the huge new demands on the troops could strain some operations.

“The vaccine issue (distribution) would be affected by this. That’s just food for thought about the ripple effect happening because of what we’re dealing with in Washington,” Ryan told reporters.

“It will probably take away from some of the vaccine distribution in some of the states if we call on them” to come to Washington,” Ryan said.

Some states have been using the National Guard to help distribute coronavirus vaccines to cities and towns as they ramp up an effort to vaccinate up to 300 million people in the United States.

The country has registered more than 22.6 million cases of COVID-19, the deadly illness caused by the coronavirus. Nearly 376,000 people in the United States have died, with no sign yet of the pandemic subsiding.

https://www.reuters.com/article/us-health-coronavirus-usa-nationalguard/sending-national-guard-to-washington-could-slow-u-s-vaccine-hand-out-idUSKBN29H0BU

Codagenix, Serum Institute Start Phase 1 Trial of COVI-VAC Single Dose Intranasal Covid Vax

 - Randomized, double-blind, placebo-controlled, dose-escalation trial

- 48 volunteers to be evaluated at three dose levels

- Endpoints include safety, tolerability and immunogenicity

- Initial data expected by mid-2021

https://www.prnewswire.com/news-releases/codagenix-and-serum-institute-of-india-initiate-dosing-in-phase-1-trial-of-covi-vac-a-single-dose-intranasal-live-attenuated-vaccine-for-covid-19-301203130.html

CDC recommends states give to anyone 65 and up

 States should expand access to Covid-19 vaccines to everyone 65 and older, as well as any adult with an underlying health condition that might raise the risk for complications of Covid-19, members of Operation Warp Speed recommended Tuesday.

The guidelines are intended to prompt faster distribution of the vaccines by making more people immediately eligible for vaccination, as well as expanding the potential locations where people can receive it. Of the more than 25 million doses of Covid-19 vaccine that have been delivered nationwide, just under 9 million shots had been put into Americans' arms as of Tuesday, according to the Centers for Disease Control and Prevention.


"Every vaccine dose that is sitting in a warehouse rather than going into an arm could mean one more life lost," Health and Human Services secretary Alex Azar said during a media briefing Tuesday, where he and other administration officials announced the recommendations.

Most states are still trying to get the vaccine to those in the first recommended phases of the rollout: health care workers, those over age 75 and front-line essential workers, such as firefighters and police officers, as well as teachers, corrections officers, U.S. postal workers, public transit workers and those whose jobs are essential for the food supply.

States will not be required to follow the guidelines. In a letter Monday to Kentucky Gov. Andy Beshear, CDC director Dr. Robert Redfield wrote that the recommendations "should not be interpreted as regulation," and that the guidance "is meant to be flexible and adaptable."

https://www.nbcnews.com/health/health-news/cdc-recommend-states-give-covid-vaccine-anyone-65-older-n1253887


Structure-guided multivalent nanobodies block SARS-CoV-2 infection, suppress mutational escape

 Paul-Albert Koenig1,2,*, 

  1. Hrishikesh Das3,
  2. Hejun Liu4,
  3. Beate M. Kümmerer5,6
  4. Florian N. Gohr2,
  5. Lea-Marie Jen
    1. DOI: 10.1126/science.abe6230
      1. PDF: 
    2. https://science.sciencemag.org/content/early/2021/01/11/science.abe6230/tab-pdf

        Abstract

        The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic continues to spread with devastating consequences. For passive immunization efforts, nanobodies have size and cost advantages over conventional antibodies. Here, we generated four neutralizing nanobodies that target the receptor-binding domain of the SARS-CoV-2 spike protein. We defined two distinct binding epitopes using x-ray crystallography and cryo-electron microscopy. Based on the structures, we engineered multivalent nanobodies with more than 100-fold improved neutralizing activity than monovalent nanobodies. Biparatopic nanobody fusions suppressed the emergence of escape mutants. Several nanobody constructs neutralized through receptor-binding competition, while other monovalent and biparatopic nanobodies triggered aberrant activation of the spike fusion machinery. These premature conformational changes in the spike protein forestalled productive fusion, and rendered the virions non-infectious.

        https://science.sciencemag.org/content/early/2021/01/11/science.abe6230.full

Assessing mandatory stay at home, business closure effects on Covid spread

 Eran Bendavid


DOI: https://doi.org/10.1111/ECI.13484


Abstract


Background and Aims: The most restrictive non-pharmaceutical interventions (NPIs)

for controlling the spread of COVID-19 are mandatory stay-at-home and business closures.

Given the consequences of these policies, it is important to assess their effects. We evaluate

the effects on epidemic case growth of more restrictive NPIs (mrNPIs), above and beyond

those of less restrictive NPIs (lrNPIs).


Methods: We first estimate COVID-19 case growth in relation to any NPI implementation

in subnational regions of 10 countries: England, France, Germany, Iran, Italy, Netherlands,

Spain, South Korea, Sweden, and the US. Using first-difference models with fixed effects,

we isolate the effects of mrNPIs by subtracting the combined effects of lrNPIs and epidemic

dynamics from all NPIs. We use case growth in Sweden and South Korea, two countries

that did not implement mandatory stay-at-home and business closures, as comparison countries

for the other 8 countries (16 total comparisons).


Results: Implementing any NPIs was associated with significant reductions in case growth in

9 out of 10 study countries, including South Korea and Sweden that implemented only lrNPIs

(Spain had a non-significant effect). After subtracting the epidemic and lrNPI effects, we find

no clear, significant beneficial effect of mrNPIs on case growth in any country. In France, e.g.,

the effect of mrNPIs was +7% (95CI -5%-19%) when compared with Sweden, and +13%

(-12%-38%) when compared with South Korea (positive means pro-contagion). The 95%

confidence intervals excluded 30% declines in all 16 comparisons and 15% declines in 11/16

comparisons. 


Conclusions: While small benefits cannot be excluded, we do not find significant benefits on

case growth of more restrictive NPIs. Similar reductions in case growth may be achievable with

less restrictive interventions


https://onlinelibrary.wiley.com/doi/epdf/10.1111/eci.13484








1,2
, Christopher Oh
1
, Jay Bhattacharya
2
, John P.A. Ioannidis
1,3,4,5,6

2020 sales of Covid-19 therapies firm up

 Gilead surprised investors yesterday with higher-than-expected 2020 guidance for Veklury, sales of which should come in at around $2.8bn, the company said. The recent Covid-19 surge was cited as a reason for the big consensus beat, presumably driven by demand in the US, where Gilead said that almost half of hospitalised patients are receiving Veklury. Usage is Europe is thought to be lower, although some countries seem to be using it more than others. The failure of several trials to establish a clear mortality benefit for Veklury caused sales expectations to be significantly reined in; perhaps the lack of other options and steroid shortages are persuading physicians to reach for what they have. 2020 sales of the antibodies approved so far, from Lilly and Regeneron, look more likely to come in where the sellside expects, recent statements from the companies indicate. The logistical problems of administering these infused therapies to pre-hospitalised patients has limited their usefulness; despite this both are seen bringing in respectable sales next year. Demand over the long term remains the big unknown with all of these products, and projections for now predict waning demand as vaccines bring the pandemic under control and, hopefully, better treatments emerge.

https://www.evaluate.com/vantage/articles/news/snippets/2020-sales-covid-19-therapies-firm

$mSales of Covid-19 products: a consensus viewSellside numbers as of early January 2021REGN-COV2 (Regeneron)Bamlanivimab (Lilly)Veklury (Gilead)20202021202220232024202520260500100015002000Evaluate




JPM: Novartis CMO Tsai on how pandemic is changing face of biopharma R&D, how pharma works

 This time last year, the life science world descended into San Francisco for the 2020 J. P. Morgan healthcare conference, doing the normal things like blowing a whole year’s budget in one day for a hotel room, shaking hands, doing deals and, if you’re like us, asking questions.

In the background, and it seemed at the time quite far in the background, was a strange new respiratory disease coming out of an area in China that looked alarming but appeared to be under control.

We fast-forward a year, and the budgets are safe, because for JPM 2021, we’re all on Eastern time, at our desks—some even in pajamas—listening virtually to what biopharma plans for the year as we continue to stay away from crowds, because that viral outbreak went from a market stall to a global pandemic in mere weeks.

That changed almost everything for almost everyone, and while some nations across Asia and Australasia have managed to tamper down the outbreak, in the West, we’re still in the thick of it, being hit by second and third waves as we desperately now start to try the mammoth task of inoculating billions of people.

Biopharma has been at the forefront of dealing with this pandemic: The drugs and vaccines created in record time will likely be the main components to bring societies out of lockdown and reset faltering economies.

It has, however, hit pharma companies hard as well: Clinical trials outside of COVID-19 have been hit by delays and stoppages because of lockdowns and concerns over viral spread.

But speaking to Novartis’ Chief Medical Officer John Tsai, M.D., at JPM this week, the challenges brought by the pandemic have been superseded by how the industry has learned to not only adapt but also excel and accelerate its research.


Tsai, formerly CMO at Amgen before being poached by Novartis in 2018, said, on an internal basis at Novartis, “When that switch flipped in March [during the first wave of the pandemic] we found that it actually unlocked a lot of innovation and it was in fact driving a lot of motivation because people had the flexibility and the freedom to work form anywhere they wanted.”

In terms of collaborations, which you would assume would be harder over the phone and via Zoom meetings, Tsai said those increased massively after March. “Even when look at our COVID trials, we started three. Typically from concept to getting a trial up and running, that usually takes us nine to 12 months. But we looked at three studies: one for hydroxychloroquine, one for [Jakavi] ruxolitinib and one for [Ilaris] canakinumab.

“We got those up in four to six weeks. So collaboration on trials like these is sky-high, and we have learned to use digital methodologies for recruitment purposes and conducted 35,000 remote monitoring visits.” These are elements to its business that Novartis will now “carry forward,” Tsai says.


What Novartis has learned during 2020 will also “accelerate how we do R&D” in the future, he adds. These days, Tsai said, he can call up pretty much all of the heads of R&D across the industry and talk about the agenda of what needs to be done as well as tap them for collabs.

If, and maybe when, there is a SARS-CoV-03, the industry will be ready because of this. Tsai also hopes that the efforts of pharma in 2020 and 2021 will be remembered. “We’re often thought about in terms of reputation for drug pricing and access,” he says, “but when pandemics hit, you turn to the life science industry for solutions because it is the science that will win through.”

https://www.fiercebiotech.com/biotech/jpm-novartis-cmo-john-tsai-pandemic-changing-face-biopharma-r-d-and-how-pharma-works