The state of the vaccines

What Pence did not get, BioNtech called its program, started in January, light speed.

Who ever gave the bioNtech head quarter in Mainz/Germany its street adresse had real sense of humor :

An der Goldgrube = at the Goldmine.
The US bought 100 million doses at $20 per dose.
Tomorrow the EU is set to sign the purchase contract for 200 million with a additional 100 million option.
Those are not pre sales agreement
The CEO of bioNtech expects to have the vaccine certified in the US and EU by mid December.

 

Luckily there is a second approval done by EMA/EU. So if the US and the EU come to the same conclusion that vaccine is safe and sound it will shut up most of the critics.

Besides competition there is this gigantic technology war going on, between mRNA and more traditional methods.

Least lets not forget its about billions, a license to print money.

 

Agreed.

 

Three pieces of news today:

The CoronaVac phase 3 trial resumed today in Brazil. The death that occurred was ruled a suicide.

American state officials are appalled at the deep cold chain needed to distribute and store the Pfizer vaccine. Many are saying it's impossible to prepare by November 15 as requested, because certain areas don't even have enough dry ice. This will be more complicated than initially anticipated.

Pfizer declined to use the distributor sponsored by the Warp Speed initiative. They said they will do their own distribution, and they have created a special box to keep the vaccine deep frozen during transport. Then upon delivery the same container can be used as storage for up to 15 days, as long as every 5 days the dry ice is replenished. Then before use, the vaccine vials can be switched to a refrigerator where they'll be good for 5 days. When the vial is diluted (each vial is for 5 doses) then those doses need to be given with 6 hours. 21 days latter, subjects need a second dose.

 

Moderna with 94.5% efficacy, with 95 infections, 90 in the placebo group and only 5 in the vaccinated group, and those 5, mild. Their mRNA vaccine doesn't only seem to prevent the disease for a large number of subjects, but even when it fails to prevent the disease, it prevents severe disease.

That is great and very encouraging, including because the Moderna vaccine, unlike the Pfizer one, can be transported in regular freezer temperatures, and stored in regular refrigerators for 30 days.

And then, it's a 100% American company whose priority, given the help it got from the NIH and from the Warp Speed Initiative, will be our domestic market.

Definitely, a light at the end of the tunnel.

They need two or three more weeks to put together the application for the Emergency Use Authorization; then it will likely take several weeks for the FDA to go through it, with an advisory committee looking at it first, then the agency itself. While waiting is excruciating, if we rush too much, we risk undermining public confidence, which is just as important as the vaccine's efficacy.

A very efficacious vaccine that nobody wants to accept, doesn't do its job. So, yes, I favor a thorough vetting of the company's data before it's approved.

 

More good news.

 

I will not go the barber and have my hair cut. I do not give a damn how I look. But a person I do not know, close to me, no way.

I would feel rather confident concerning the vaccines, bioNtech ore Moderna. Both of their studies and Phase 3 have gone without a hitch. If both get approved in the US and Europe, I would take them with no second thought.
I do not trust the current government, I believe in the integrity of the people who work and oversea the approval process.
That is about all we can do.

 

Moderna still has to be stored at -20.

Curevac is testing its prototype at storage temps of a normal freezer, 5C.

https://www.msn.com/en-us/money/com...-freeze-challenge-with-covid-shot/ar-BB1aXah3.

Three mRNA vaccine and 3 different approaches.
Curevac signed a sales agreement with the EU for over 400 million doses, naturally based on approval.

 

What of the Russian Sputnik vaccine?

Any good information? It is months ahead of others.


Moi

​

 

No, they are not month ahead. They announced a vaccine without having started Phase 3 testing, some month ago.
As of now, I have not heard about any of the results of Phase 3.
Currently, I would put a HUGE question mark behind Sputnik.
Accordingly to press releases Russia has not jet secured production capacity for Sputnik.

 

https://www.firstpost.com/health/sp...t-effectiveness-against-covid-19-9014551.html


I looked it up.
Phase 3 results just released. 90+% effective
and no ultra cold storage required.

It stimulates both antibodies and cellular immunity.


Moi

​

 

That's not off-topic. This thread is to talk about the vaccines and your wife's question is very appropriate.

I can't 100% reassure your wife, but I can say that the size of the phase 3 trials is appropriate. The Moderna one, a bit on the minimum size, 30.000 subjects. The Pfizer one, a bit better, almost 44,000 subjects. So, even thought the scientific community acted fast, the politicians secured the funding fast and cut down on the red tape, and the biotech firms launched into a huge effort to expedite things, the SAFETY aspects themselves weren't badly curtailed. Generally, the minimum numbers go like this: Phase 1 40 people, phase 2 600 people, phase 3 30,000 people. Moderna being small and not having managed all three phases before, they went for the minimum numbers. Pfizer, a vastly more resourceful company, had the luxury of pushing the numbers a bit. But even though Moderna got the minimum acceptable sizes, they ARE acceptable sizes.

So, the FDA is requiring 60 days post 2nd dose of the vaccine for observation of adverse events, before considering the Emergency Use Authorization. We're about to reach that landmark for both vaccines, and so far, there hasn't been any serious reaction with these two. Unlike the Oxford/AstraZeneca, and the Johnson and Johnson, which both had to halt trials temporarily due to adverse events, it didn't happen to Pfizer and Moderna.

So, as far as we know, these vaccines are safe. I'd say, much, much safer than catching the virus. We are seeing complications in 1 in 10 people who catch Covid-19... and we just had 15,000 people taking the Moderna shot with ZERO serious reactions, and 23,000 people taking the Pfizer shot with ZERO serious reactions. These are MUCH better odds than 1 in 10, no?

Now, can we be ABSOLUTELY sure that there will be no unforeseen post-market reactions? No. But that's valid for ALL medications and vaccines known to man. We do the phase 1, 2, and 3 trials, apply for authorization, and then launch the drug or vaccine into the market. There is no other way to do it.

Otherwise it would be a catch 22... if we couldn't put a product in the market because there isn't post-market experience, since there will never be post-market experience without launching the product.

Therefore, a tiny possibility of risk always exists...

But again, the risk of the natural disease is much bigger, so, in your wife's shoes, I'd take the vaccine (and in my own shoes too, since I intend to take it at the first opportunity).

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Fever: yes, scary. The virus is totally out of control, right now. Be safe! By the way, I'm giving my wife haircuts, and vice-versa. If we were to fail at being medical doctors, we would be able to open a hair salon, LOL.

When I gave her a hair cut, I was really surprised with the good results! She looks super cute with the job I did!!!

But yes, we do not want to go to gyms, salons, bars, restaurants, any of these places. We will, once we get vaccinated. Not before. The way this virus is out of control right now, it takes only a little lapse of attention to catch it. And so close to the vaccines, it would be really stupid to allow oneself to contract this dangerous virus.

 

Yes, the Sputinik is in trouble. They are having trouble keeping it stable, and they are not able to ramp up production. Despite their bold claims and plans for mass vaccination, they have been completely unable to take off. They did approve it before Phase 3, and I have read their phase 1 trial paper that they sent to the Lancet, and frankly, the data were suspect and looked made-up. I wouldn't trust the Sputinik-V at all. It's the vaccine I trust the least, or actually just plain don't trust.

 

Household freezers are usually calibrated for -18C or lower.
Normal freezers are not 5C. This is the temperature for a refrigerator, not a freezer. Curevac is aiming for refrigerator temps, not freezer temps.
Medical freezers reach down to -50C.
Pfizer needs SPECIAL freezers that reach down to -70C which is -94F . Regular medical freezers won't do. The special ones cost $20,000 and are in short supply, with a wait of 6 weeks for delivery.

Pfizer did design some special boxes for transport with dry ice and the same boxes can be used to keep the vaccine unspoiled for up to 15 days, replenishing the dry ice every 5 days. It's gotta be dry ice in pellets, and the containers are for 5,000 doses. This is complicated for small rural hospitals and clinics. The Pfizer vaccine does hold for 5 days in a regular refrigerator once taken out of the container but once a multi-dose vial is opened it must be used within 6 hours.

Here, a bit on medical refrigeration:

https://k2sci.com/news/a-quick-guide-to-medical-refrigerator-temperature-monitoring/

Pfizer's requirements:

https://www.cbsnews.com/news/vaccine-covid-19-pfizer-cold-storage-logistics-nightmare/

So, good that Curevac is trying that, but Moderna's requirements are already pretty good. Not to forget, the Moderna vaccine can be kept in a regular refrigerator for up to 30 days.

 

If I am given a choice between the Pfizer and the Moderna products, I'll pick the latter. It was tested in fewer people but I trust more that the simpler cold chain was not breached and the shot I'm getting is not spoiled by higher temperature than what it can withstand.

I think the deep cold chain for the Pfizer product will indeed become a problem. How does one know if your local Walgreens did a good job keeping it cold enough?

When you open the special cases Pfizer is manufacturing, you can open it for a maximum of 3 minutes, and only twice a day.

 

I would not get on a airplane, they are spreaders.
I consider 2020 and most of 2021 as lost years. Forget about Thanks Giving and Christmas, stay home, so we have many more in the future.

My county went red, as expected, 332 cases on Friday, 449 today.
Will be interesting how our commissioners will react, they meet today.

 

I wouldn't travel, and especially not by plane. It's not even just the airplane itself, but the crowded airports. Remember, an airport is an indoor environment. Clouds of aerosol may be floating around. The virus is out of control and spreading fast and it is really contagious. You'll have to use an airport or airplane restroom (or both). What if the person using it right before you, leaves behind an aerosol cloud and you breathe it in?

 

Breaking news: The CoronaVac had phases 1 and 2 published, peer-reviewed; Lancet (freshly published 3 hours ago). 143+600 subjects. Spectacular results. Seroconversion to neutralizing antibodies reached a whooping 100% in one of the doses (6mcg) after the second dose when done 28 days apart (slightly less for other doses and intervals - 92%, 97%, and 98%). The company picked the 3mcg dose which was more favorable in terms of side effect profile and only dropped seroconversion to 97% from the 100% of the 6mcg dose.

Here is the Lancet paper:

https://www.thelancet.com/journals/laninf/article/PIIS1473-3099(20)30843-4/fulltext

The CoronaVac stays stable for 3 years in refrigerators. No need for freezer. This is an advantage.

By now, it seems like the SARS-CoV-2 is a virus that is EASILY prevented with vaccines. We have several platforms with outstanding results, way beyond expectations (mRNA, inactivated virus, and the Novavax's protein subunit has had good results too).

Of course, we still need to see the phase 3 results for the CoronaVac, which are almost ready, although in a relatively small population. The Chinese were planning to have a large phase 3 in Bangladesh but that trial ended up not happening due to local issues, so they were left with the 13,000 Brazilian healthcare workers, and the smaller trials in Turkey and Indonesia which are far from being over. On the other hand, the 13,000 Brazilians are all highly exposed; they are healthcare workers taking care of Covid-19 patients so they might be enough for separation from placebo. This would still leave us with not enough testing for safety... but the company did give the vaccine to 52,000 of their own employees in China, and while it wasn't an RCT, they did follow them up for adverse reactions and had no serious ones. I think that if the 13,000 Brazilians provide the efficacy part and the 52,000 Chinese provide the safety part, we'll have sufficient evidence of the safety and efficacy of the CoronaVac.

 

So, what is going on with the Sputinik V, the Russian adenovirus vector vaccine?

The Russians have released preliminary results of their Phase 3 trial. The total number of participants is 40,000 volunteers. Of which, 20,000 have received just the first dose, and among these 20,000, 16,000 have received the second dose.

So 4,000 of these 20,000 are still scheduled for the 2nd dose, and they need to vaccinate the other 20,000 to complete their phase 3 trial.

They did release preliminary results for the 16,000 volunteers who already took the two doses: 92% efficacy.

So, this is good. We now have 3 vaccines that have phase 3 efficacy data (two of them, complete; one, preliminary).

What do we have, so far?

Pfizer, 95% efficacy, all 43,000 and change subjects have been given the two doses. Phase 3 is 100% complete, and they are now preparing the paper for publication and for EUA (emergency use authorization) application. From the subset of data, the Pfizer/BioNTech product yielded 94% efficacy in the subgroup of volunteers older than 65. Remember, Pfizer initially only had 30,000 subjects like Moderna, but they spontaneously extended their trial to include more minorities and more seniors.

Moderna, 94.5% efficacy, all 30,000 volunteers got the two doses. They have also concluded their phase 3 and are preparing for publication and application, just like Pfizer. Their CEO said in an interview "the vaccine doesn't seem to lose efficacy in the elderly" but they did not quantify this statement with a percentage.

Gamaleya (Sputinik V), 92% efficacy in partial results of phase 3 which hasn't concluded. It is conceivable that once all 40,000 volunteers get the two doses, these numbers will change. Also, they based their efficacy percentages on 20 confirmed cases of Covid-19, while the statistical power of the Moderna and Pfizer numbers is greater, given that they based their numbers on more than 90 confirmed infections.

So, why did Gamaleya release this partial result about 16,000 volunteers with only 20 confirmed cases which doesn't meet the usual threshold for preliminary analysis? I guess, not to fall behind the news cycle, given the Pfizer and Moderna announcements.

Do I trust the Russian announcement? No. But we can always hope that they are a bit behind in their phase 3 but not malicious and the 92% will hold. We'll see.

Production and distribution:

Pfizer is doing all they can to ensure that their deep cold chain will hold. They purchased a large number of -70C freezers, maybe even above their needs. They said, "if we over-purchased, we over-purchased." In other words, this multi-billion dollar Big Pharma company can afford it. They also developed their dry ice boxes to keep the vaccine below the minimum temperature for 5 days in transport, renewable two more times by replenishing the dry ice for up to 15 days. This should be enough. Everybody is nervous, though, with the possibility of unreported breakdowns of the cold chain. So they decided to avoid the Warp Speed distribution contractor and the company will directly deliver the vaccine to the vaccination points. That is good. So I think ultimately we can trust them.

Pfizer's production numbers: 50 million doses by the end of 2020, and 1.3 billion doses by the end of 2021.

Moderna: much easier distribution. They will use the Warp Speed contractor. They only need regular -20C freezers; the vaccine stays good for 6 months in a regular household or medical freezer, and then, 30 days in a refrigerator.

Moderna's production numbers: they are partnering with a Swiss pharma company for production and expect to be able to make 1 billion doses by the end of 2021,

Sputinik V - Who knows? Last I heard, they were having trouble with stability, and with bumping up production capacity.

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OK, so these are the ONLY 3 that have had PHASE 3 EFFICACY data.

Don't mix up these numbers with the immunogenicity shown by Sinovac/Butantan's CoronaVac (97% to 100% of neutralizing antibodies) and Novavax (100% of neutralizing antibodies). These numbers bode well for efficacy but are NOT YET efficacy numbers. This POTENTIAL for efficacy still needs to be put to the test of phase 3 trials (that is, to see how many confirmed Covid-19 cases occur in vaccinated volunteers versus volunteers who are given a placebo shot).

What about the Oxford/AstraZeneca, once the frontrunners? Well, as you all abundantly know by now, they had trouble with their phase 3 trial, with a case of MS, and a case of transverse myelitis. It derailed and delayed their phase 3. Therefore, so far we have NO INFORMATION about Oxford/AstraZeneca's efficacy. The trials have resumed as ultimately the cases were considered to be unrelated to the vaccine but they got several weeks behind Pfizer and Moderna.

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Personally, how would I pick one of these, if they were all available to me right now and I could pick just one?

By order:

1. Moderna/NIH. Better odds that their cold chain won't break down. Excellent efficacy. No serious reactions.

2. Pfizer/BioNTech. Excellent efficacy, no serious reactions in a larger phase 3 trial than Moderna's but bigger risk of deep cold chain breakdown which is why I place it behind the Moderna one. If I could be 100% reassured that the dose being injected into me never got above the required temperature, then I would prefer the Pfizer product due to the larger trial and the efficacy for older people unless the final results of the Moderna are also good among older volunteers. Which is weird because as far as I know, their phase 3 only had volunteers aged 18-60 so I don't know how they say that it didn't lose efficacy in older people.

3. Sinofarm/Butantan CoronaVac. Efficacy data not in yet, but immunogenicity looks great and safety data benefits from the 52,000 company employees who were given it, with no serious reactions. True and tried method (inactivated virus).

4. Novavax. Still far behind but looking great in all phases already completed. Good platform (protein subunit).

5. Oxford/AstraZeneca. Unknown efficacy. Did result in two serious reactions although later, they were cleared, but while I have no problem with clearing the MS case, I'm more suspicious of the TM case. But I don't have access to the TM case information, and the Brits and the FDA ultimately cleared them to resume phase 3, so I guess it's all good.

6. Gamaleya Sputinik-V. If you believe in their information, it looks good but phase 3 is still half-way and I simply don't trust the Russians with their information. I'd have said the same of the Chinese but they do have the Brazilians vouching for them and I do trust the Brazilians (Butantan is a high quality and ethical institute; I personally know many of their scientists) so I don't even question the Chinese data, but I still do question the Russian data.

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The CoronaVac and the Sputinik-V are obviously not coming to America. So over here, we'll have the Pfizer, the Moderna, the Novavax, and the Johnson and Johnson. The latter ran into phase 3 issues too... And Novavax is farther behind.

So I think that in a first phase, most Americans will have to pick between Moderna and Pfizer. I mean, that, once we get to the general distribution phase with these being available in your neighborhood walk-in urgent care clinic or your local pharmacies. Those who will get them through employment or some governmental initiative (health departments) probably won't have a choice; it will depend on which one got delivered to that organization.

Since I work in a hospital, that's how I'll get mine; we healthcare workers will be in one of the priority waves. I'm hoping that my hospital gets the Moderna one, but I'll take the Pfizer one too if that's what we get, crossing my fingers for the integrity of the deep cold chain.

 

What will happen to the other vaccines being developed, but much farther behind? There is still space in the market for the first several. At one point the other efforts will be dropped, beyond the first several. Read this - this article calls it safe up to the sixth one approved, as a way of speaking:

https://qz.com/1934632/what-happens-to-the-other-covid-19-vaccine-candidates/?utm_source=YPL

 

I read that article today. A rather well funded company like curevac will continue. Especially since its storage temps goes from 41F to -70.
Even that they will start phase 3 by the end of the year, they still will have a huge market, if their vaccine has bioNtech or Moderna data.
The 4 billion number needs some explanation, does it mean complete immunization of people, which would mean with double shot vaccines only, 8 billion shots.
That is a huge number.
BioNtech says they can produce 750 million doses in Europe in 2021, which would cover 375 million Europeans out of 500 million.
So basically, current figures would just cover the US and Europe.

There is still a huge market left.
If you have a mRNA, 95%, with a huge temp spread, 41F to -70F you can not do wrong.
Till the whole world has reached some immunization level will take years. We have jet to find out how long those shots last, 1, 2, 3 Years or even longer.
So the market is still wide open.

BioNtech still has some home work to do, if the temps figures from curevac are right. They are number one on the vaccine, but I like the approach of curevac, if they have the temp problem solved and a very good vaccine, they might have something for the long term, maybe June or July and for future vaccines.

 

Yes, the vaccines sponsored by Warp Speed and/or CEPI should be able to continue R&D and production given that they have little to lose, from counting on funding for cost sharing and grants.

CEPI initiative has 9 vaccines:

• Inovio, United States of America (Phase I/II)
• Moderna, United States of America (Phase III)
• CureVac, Germany (Phase I)
• Institut Pasteur/Merck/Themis, France/ United States of America /Austria (Preclinical)
• AstraZeneca/University of Oxford, United Kingdom of Great Britain and Northern Ireland (Phase III)
• University of Hong Kong, China (Preclinical)
• Novavax, United States of America (Phase I/II)
• Clover Biopharmaceuticals, China (Phase I)
• University of Queensland/CSL, Australia (Phase I)

The Warp Speed Initiative has these 8:

Directly funded:

Johnson and Johnson
Moderna/NIH
Oxford/AstraZeneca
Sanofi/GlaxoSmithKline

Indirectly funded

Inovio
Vaxart/Emergent Biosolutions

No R&D funding but advance purchase orders have been established for two additional companies:

Novavax
Pfizer/BioNTech

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Now, there are five other vaccines in advanced stage that don't have CEPI funding or WSI funding, but are funded by the governments of Russia and China, and the government of the states of São Paulo and Paraná, Brazil:

Sinovac/Butantan - CoronaVac (China, State of São Paulo, Brazil)
Gamaleya - Sputinik V (Russia, State of Paraná, Brazil)
Cansino Biologics (China)
Sinopharm-Beijing/Chinese CDC (China)
Sinopharm-Wuhan Institute of Virology (China)

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So these are the well-funded vaccines. 9 from CEPI, 8 from the WSI for a total of 13 since 4 of these overlap with double-funding, plus 5 from other governments.

Therefore, 18 vaccines are well-funded and likely to succeed (at least, as far as funding and infrastructure go - most, with efficacy and safety still to be determined).

Assuming that all the above vaccines are proven to be safe and efficacious, I'd think that if you look at countries/regions in the world, we'd have these main markets, and I'll add which ones I think are likely to prevail there:

North America:

United States - Moderna/NIH, Pfizer/BioNTech, Novavax, Oxford/AstraZeneca, Johnson and Johnson, and running behind, Inovio, and Sanofi/GSK
Mexico - they have agreements to buy vaccines from Oxford/AstraZeneca, Pfizer/BioNTech, Cansino Biologics, and another Chinese corporation called Walvax. They are also making their own which might be ready by the spring, from Laboratorio Avimex in partnership with UNAM (their best university) and the Mexican Social Security Institute.
Canada - Peculiar case. They have secured 300 million doses... but their population is much smaller than half of that (most vaccines need two doses). They have purchase agreements with Pfizer/BioNTech, Moderna, Johnson and Johnson, Novavax, and 72 million doses from Sanofio/GSK

European Union - Pfizer/BioNTech, Oxford/AstraZeneca, Curevac, Moderna made locally in Switzerland by Lonza, and running behind, Pasteur/Merck/Thamis, and Sanofi/GSK

China - Cansino, Sinopharm-Wuhan-CDC, Sinopharm-Beijing, Sinovac CoronaVac, and running behind, University of Hong Kong, and Clove Biopharmaceuticals

India - Oxford/AstraZeneca, and Novavax, both made locally by the Serum Institute of India (largest vaccine maker in the world - they are also considering local production of the Sputinik V)

Central and South America

CoronaVac made locally in Brazil by Instituto Butantan and to be exported to other South American countries, Oxford/AstraZeneca made locally in Brazil by Fiocruz for domestic use only, and Sputinik-V, made locally in Brazil by União Química and the State of Paraná for domestic use only. Most other South American countries are planning to get their vaccines from either Brazil (CoronaVac) or Argentina (Oxford/AstraZeneca). In addition to purchasing 25 million doses of the Sputinik V directly from Russia for domestic use, Argentina will also make locally the Oxford/AstraZeneca vaccine for domestic use and exports to other South and Central American countries.

Russia - Sputinik V

Australia - Novavax, University of Queensland/CSL

Japan - Moderna and Novavax, in partnership with Takeda Pharmaceuticals, in addition to a Pfizer/BioNTech's contract with the Japanese government

South Korea - Sputinik V, produced locally by GL Rapha. They have a domestic effort to make their own, by Genexine, a DNA vaccine called GX-19, in phase II. They plan to supplement their stock by purchasing an additional 20 million doses from some other maker, but they haven't picked one yet and don't seem very eager to get Moderna or Pfizer.

Africa

Only South Africa is strongly positioned, having secured agreements with Oxford/AstraZeneca, Johnson and Johnson, and Novavax (the latter, through the Serum Institute of India).

SubSaharian Africa - very uncertain. The WHO COVAX initiative is supposed to subsidize Covid-19 vaccines for poor African countries but nobody knows which ones and when they will be available to these populations - some are already saying it will be AFTER the end of the pandemic, since the rich countries are gobbling up the available production capacity, as detailed above.

Middle East

Qatar: Pfizer/BioNTech
Kuwait: Pfizer/BioNTech
Lebanon: Uncertain, hoping for help from WHO's COVAX
Israel: Pfizer/BioNTech
Egypt: 20% of the population will get Pfizer/BioNTech and 30% Oxford/AstraZeneca. No plans to cover the other 50% yet.
Jordan: Pfizer/BioNTech
Iraq: Counting on WHO's COVAX