19 ms·

Some had faith in the new mRNA technology, while others preferred to rely on more time-tested methods. Sometimes articles hide a great deal in one seemingly in

Some had faith in the new mRNA technology, while others preferred to rely on more time-tested methods. Sometimes articles hide a great deal in one seemingly innocuous sentence. From what I've learned from Europeans, there's only one vaccine candidate of that nature the EU considered, a Sanofi Pasteur/GlaxoSmithKline combo, the former providing the infamous spike protein, the latter an adjuvant. Everyone expected this to work like the Novavax version of roughly the same thing that's just reported good U.K. trial results, but Sanofi/GSK's didn't provide a good enough response in the elderly. They were expected to fulfill up to half of the EU's requirements, but they're restarting with a new Phase I trial next month or so, and they might have something ready by the end of 2021. So if all that is correct, the EU ended up with a very big hole in their plans and not enough redundancy. By comparison only because I'm in the USA and familiar with our efforts, 5 big bets were made with more than a billion dollars each in up front R&D money. Moderna and now Novavax are looking very good, AZ/Oxford and one dose of Johnson and Johnson's is looking OK, with a two dose study in progress for the latter that might show increased efficacy, and only Sanofi/GSK failed in a really major way.

maxerickson 6y ago
EU pre-ordered more Pfizer than the US. Enough for 150 million people in EU, vs enough for 50 million in the US. The US has ordered more after it was approved.
- outside1234 6y ago
  The EU did not pay as much as the US — and signed the contracts much later. Pfizer is doing the rational actor thing and, given a shortage, prioritizing their highest paying clients. There might also be verbiage in the US contract to this effect. Also, Pfizer is an American company.
  - Throwawayaerlei 6y ago
    There might also be verbiage in the US contract to this effect. Also, Pfizer is an American company. But also a multinational, manufacturing their vaccine in the US and Belgium. Initially without any help from Operation Warp Speed, which appears to be a mistake if their December claims about supply chain problems was true, along with eventually signing up to the program and moving up their promise for our second 100 million doses from the 3rd to 2nd quarter. But that Belgium plant? Something is so wrong with it they're shutting it down for a while to improve capacity ir so they claim. My only good guess is that they have a sterility problem and are finding they have to dump way too many lots they produce after testing for that.
    - jack_arleth 6y ago
      As a Belgian, this is what we've heard and read: - Pfizer stated on 15 Jan 2021 that they would produce 40% less (60.000 instead of 100.000 doses) - This delay in production would we compensated in the weeks that follow. In February the production should be compensated. - This was a temporary measure to scale up production after an extra order was made by the EU The working group concerning the vaccine and it's distribution was to quote "not amused" by this news and wrote a sternly worded letter. Source:https://www.vrt.be/vrtnws/nl/2021/01/16/versnelde-inenting-ziekenhuispersoneel-loopt-mogelijk-vertraging/ https://www.vrt.be/vrtnws/nl/2021/01/16/versnelde-inenting-z... Text in Dutch.
      - hef19898 6y ago
        Your last point, the additional order, is crucial. And media, Spiegel being one of the most outspoken, created enough pressure tp force that order. Not that overall quantity was an issue, so. But all people saw was shortages. There were no delivery schedules published, so that played a role. But I would have expected some more investigation and research. Then thr EU ordered more, being under fire, and that let to a temporary shutdown of the plant and even more severe shortages. Nobody is thinking about that. Instead, the Spiegel is using this to push an agenda against von der Leyen. I'll not defend her, she should never have gotten the presidency (EDIT: become head of the Commission) but what is going on now is just cheap propaganda. And definitely not helping in any way.
  - foepys 6y ago
    The US does currently not allow COVID-19 vaccine exports. Pfizer's plants are only manufacturing for the US while the EU plants are producing for the EU, Isreal, Canada, UK, etc.
    - slim 6y ago
      coul EU ban vaccine export?
      - Macha 6y ago
        They tried a retaliatory ban against the UK yesterday over the AstraZeneca situation (vaccines in EU plants were exported to the UK last month because the UK were readier to rollout sooner, the UK is not allowing exports from UK plants in return, leaving the EU with a shortfall on vaccines), but because of the way it involved the Northern Ireland border rules agreed in brexit they faced strong opposition from Ireland, also an EU member and I think they've backed down for now
  - jorvi 6y ago
    > Also, Pfizer is an American company. BioNtech is a German company. If it would come down to national egotism, BioNtech would just kill the licensing deal and Pfizer wouldn't be allowed to produce anything.
    - petre 6y ago
      I think there are consequences steming out from killing a contractual agreement. They can however license Sanofi and others to produce the vaccine, which is what will be eventually done.
    - thepasswordis 6y ago
      >Pfizer wouldn’t be allowed to produce anything. Pfizer wouldn’t be allowed to stop producing anything.
  - saiya-jin 6y ago
    Ah yes the good old covid story - sovereign states order some medicine/medical equipment from the companies, and on the airport upon sending it to the country comes US government officials with few extra (freshly printed) suitcases of money to change delivery of that order. Remember quite a few articles from spring about that. 3rd world countries having no chance of receiving what was agreed upon. I mean I understand, when SHTF its everybody for themselves and fuck the rest. I guess in some twisted view a human nature. But I really have to severely twist it and leave any morals behind the door. Next time somebody will be praising US as some force of good in this world, well they can go fuck themselves too. /rant
    - deathgrips 6y ago
      Covid is not nearly as high on the priority list for many third world countries as it is for the US. Here covid shuts down everything. In many African countries it is an order of magnitude less impactful than malaria.
      - estaseuropano 6y ago
        There's less testing, less reporting and much less transparency and awareness. Doesn't mean there's less infection or less dying.
        gridder 6y ago
        There probably is (less infection) due to the more broad vaccines they receive compared to developed countries, which as a second effect create a little more broad immunity.
        ChrisIsTaken 6y ago
        Due to the much younger population, most of Africa, India, and Pakistan has had MMR, and it's been found that the mumps vaccine provides significant immunity. In the west most over 35 had measles only, or MR combination without mumps. DOI: 10.1128/mBio.02628-20 For some reason this hasn't been well covered in the media. I got an MMR booster in June based on preliminary findings, my GP thought I was insane.
mrtksn 6y ago
Chinese and the Russian vaccines were not even considered. Now those are used in mass vaccinations, soon EU would be behind all countries but those who barely have any government at all. People don't even want to talk about that, as if those alternatives don't exists. Non-EU countries in Europe are getting them. Serbia(6.1) and Turkey(2.3) are already close to EU average(2.6) or better on the vaccination process.
- smnrchrds 6y ago
  > EU would be behind all countries but those who barely have any government at all. Ouch. Reading this from Canada hurts. (We are way behind EU and I would be very surprised if we get ahead of them at any point).
  - macromagnon 6y ago
    Canada has no large scale vaccine production capacity so even if they could license the production they couldn't produce any decent amount any time soon.
    - katbyte 6y ago
      I hope this is something that changes post pandemic.
      - macintux 6y ago
        I just hope there is a post-pandemic era. Too many unknowns still about the mutations and whether they’ll out-maneuver the vaccines.
        maxerickson 6y ago
        Lots of reason for optimism. The vaccines can be retargeted, and like the flu vaccine, approved with a faster trial. And the mRNA vaccine production can continue to scale up. So if there is a need for a new vaccine, we can likely deploy it with a shorter interval to availability and much larger initial volume. We can also become more disciplined. We don't need to go all the way to a strictly enforced lock down to improve on the social distancing that we've done the last year (at least, not in the US). And we can try to get people to more widely accept contact tracing/tracking.
digikata 6y ago
I wonder why not cover younger people with the GSK version and older people with some other vaccine?
- Throwawayaerlei 6y ago
  Excellent question. Probably the biggest factor is that Phase III trials are insanely expensive, like a billion dollars plus or minus. High touch, 30,000 people minimum for the US, lasts two years, etc. Sanofi/GSK is hazarding some of their own money in this, and has to look at the market for COVID-19 vaccines, which is obviously weighted towards the elderly. Might also be risk management in wondering if the final results for the younger would be disappointing or worse, this problem with the elderly was learned through surrogate endpoints from serological as in blood testing of immune system responses. See Oxford for how they were led astray from their first big 500 Phase I/II people test of their vaccine platform, and achieved much worse results than they anticipated when put in the crucible of multiple Phase III trials and the real endpoints of getting COVID-19, or serious cases of it.
  - sampo 6y ago
    > Phase III trials are insanely expensive, like a billion dollars plus or minus Do you have a source for that? JAMA Internal Medicine says a median of 19 million, but that's for all drugs, not specifically vaccines. https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2702287 https://jamanetwork.com/journals/jamainternalmedicine/articl...
    - Throwawayaerlei 6y ago
      Not a good or recent one, but reading the linked article indicates the sort of trials being done for vaccines will have a median much greater than the $19 million you cite. These trials enroll 30,000 subjects at minimum, and take 2 years, both of which substantially exceed the maximums cited in the paper that they or anyone else they knew of had tried. In the case of length, by 4 times. Thinking further, a billion is too high an estimate today, because these trials or one I looked closely at use smartphone "ediaries" to reduce the number of direct person to person contacts. But they're still high touch affairs, nothing substitutes for phone calls and direct examinations, although the latter are limited in number, but start with a general medical exam. Thanks for bringing that paper to my attention, I'll look more closely at it later.
neximo64 6y ago
You're saying this despite the weekly pcr and different efficacy testing methods?
- Throwawayaerlei 6y ago
  Can you be more specific? I'm happy to drill down to the individual Phase III trial protocols, but want to know which ones you're referring to. Plus I'm pretty sure I left myself a lot of wiggle room with efficacy claims like "very good" and "OK."
  - neximo64 6y ago
    Some of the efficacy methods involved you saying you're sick and then getting tested (Pf/Mod). Others were you were swabbed weekly (thereby catching asymptomatic infections (AZ)). So the efficacy rates between the bunch aren't apples to apples comparisons. AZ has an understated efficacy rate, so it's better than 'OK'. It explains Jansens efficacy being broken down up to the number of hospitalisations (where it reduces nearly all of them)
    - Throwawayaerlei 6y ago
      AZ has an understated efficacy rate, so it's better than 'OK'. Maybe, but their and Oxford's testing has been such a mess, with more than one lie promulgated by AZ in public claims (the blended efficacy based on an appalling Oxford mistake that suggested a better dosing that later didn't pan out), that I don't have much confidence in their current Phase III claims. Which date back to early December and haven't been publicly updated. Those are based on 4 trials in different countries, less than 6,000 each for the official 21 day apart dosing and a 70% efficacy claim.
TheMechanist 6y ago
Gentlemen, the hole is due to the fact that no company has the large scale productive capacity for the newly discovered COVID-19 vaccine. Ordering earlier and paying more would just have shifted distribution around, and would not have made more doses available. Every vaccination done in the US or the UK means one less vaccine dose for Europe. And that is not "ducking responsibility", it is basic logic - as one cannot fit 10 pegs in 9 holes, one cannot vaccinate 10 people with 9 doses.
- mauritzio 6y ago
  Well the fact that the companies own the stuff that was researched with tax payer money, which then tax payer money must buy again also doesn't help to scale. As there is no real market but just an oligopol of producers. If the formulas would be public domain, the producers can compete who is fastest and there would be much more and they still earn good money...
- anonuser123456 6y ago
  Your model seems to assume a fixed production capacity? It would seem plausible that if you paid an extra billion or two, companies could find a way to scale up production faster.
thetis 6y ago
I just have been sollicitated to test the Janssen/Johnson and Johnson. Seems that it is still in Phase III in Western Europe. I'm not 100% sure to want to participate, split between: ok there is enough vaccine i'll be vaccinated in 3m OR OK i need to do this because we need more vaccines.
- Throwawayaerlei 6y ago
  Janssen has finished recruiting for their 1 dose Phase III trial, but is still doing that for their 2 doses 8 weeks apart trials, this huge one https://clinicaltrials.gov/ct2/show/NCT04614948 https://clinicaltrials.gov/ct2/show/NCT04614948 and this small one in the US and Belgium https://clinicaltrials.gov/ct2/show/NCT04436276 https://clinicaltrials.gov/ct2/show/NCT04436276 There reporting on their one dose trial's efficacy results is pretty good, about what I expected, so if this gets you that one first dose ASAP its seriously worth considering. It's also a relatively mature platform, used previously for their Ebola vaccine which passed an European Phase III trial, but wasn't the earlier one that made such a difference in the last outbreak. The other vaccines you might get are less mature platforms, AZ/Oxford 2 doses 21 days apart has less efficacy than Janssen's 1 dose (Oxford had not before 2020 ever tried testing their platform on more than 40 people at a time), the mRNA vaccines I'm sure you've heard all about, but I wouldn't make any bets on when Pfizer will be able to provide you a dose from their currently? closed Belgium plant.

maxerickson 6y ago

EU pre-ordered more Pfizer than the US. Enough for 150 million people in EU, vs enough for 50 million in the US. The US has ordered more after it was approved.

outside1234 6y ago
The EU did not pay as much as the US — and signed the contracts much later. Pfizer is doing the rational actor thing and, given a shortage, prioritizing their highest paying clients. There might also be verbiage in the US contract to this effect. Also, Pfizer is an American company.
- Throwawayaerlei 6y ago
  There might also be verbiage in the US contract to this effect. Also, Pfizer is an American company. But also a multinational, manufacturing their vaccine in the US and Belgium. Initially without any help from Operation Warp Speed, which appears to be a mistake if their December claims about supply chain problems was true, along with eventually signing up to the program and moving up their promise for our second 100 million doses from the 3rd to 2nd quarter. But that Belgium plant? Something is so wrong with it they're shutting it down for a while to improve capacity ir so they claim. My only good guess is that they have a sterility problem and are finding they have to dump way too many lots they produce after testing for that.
  - jack_arleth 6y ago
    As a Belgian, this is what we've heard and read: - Pfizer stated on 15 Jan 2021 that they would produce 40% less (60.000 instead of 100.000 doses) - This delay in production would we compensated in the weeks that follow. In February the production should be compensated. - This was a temporary measure to scale up production after an extra order was made by the EU The working group concerning the vaccine and it's distribution was to quote "not amused" by this news and wrote a sternly worded letter. Source:https://www.vrt.be/vrtnws/nl/2021/01/16/versnelde-inenting-ziekenhuispersoneel-loopt-mogelijk-vertraging/ https://www.vrt.be/vrtnws/nl/2021/01/16/versnelde-inenting-z... Text in Dutch.
    - hef19898 6y ago
      Your last point, the additional order, is crucial. And media, Spiegel being one of the most outspoken, created enough pressure tp force that order. Not that overall quantity was an issue, so. But all people saw was shortages. There were no delivery schedules published, so that played a role. But I would have expected some more investigation and research. Then thr EU ordered more, being under fire, and that let to a temporary shutdown of the plant and even more severe shortages. Nobody is thinking about that. Instead, the Spiegel is using this to push an agenda against von der Leyen. I'll not defend her, she should never have gotten the presidency (EDIT: become head of the Commission) but what is going on now is just cheap propaganda. And definitely not helping in any way.
- foepys 6y ago
  The US does currently not allow COVID-19 vaccine exports. Pfizer's plants are only manufacturing for the US while the EU plants are producing for the EU, Isreal, Canada, UK, etc.
  - slim 6y ago
    coul EU ban vaccine export?
    - Macha 6y ago
      They tried a retaliatory ban against the UK yesterday over the AstraZeneca situation (vaccines in EU plants were exported to the UK last month because the UK were readier to rollout sooner, the UK is not allowing exports from UK plants in return, leaving the EU with a shortfall on vaccines), but because of the way it involved the Northern Ireland border rules agreed in brexit they faced strong opposition from Ireland, also an EU member and I think they've backed down for now
- jorvi 6y ago
  > Also, Pfizer is an American company. BioNtech is a German company. If it would come down to national egotism, BioNtech would just kill the licensing deal and Pfizer wouldn't be allowed to produce anything.
  - petre 6y ago
    I think there are consequences steming out from killing a contractual agreement. They can however license Sanofi and others to produce the vaccine, which is what will be eventually done.
  - thepasswordis 6y ago
    >Pfizer wouldn’t be allowed to produce anything. Pfizer wouldn’t be allowed to stop producing anything.
- saiya-jin 6y ago
  Ah yes the good old covid story - sovereign states order some medicine/medical equipment from the companies, and on the airport upon sending it to the country comes US government officials with few extra (freshly printed) suitcases of money to change delivery of that order. Remember quite a few articles from spring about that. 3rd world countries having no chance of receiving what was agreed upon. I mean I understand, when SHTF its everybody for themselves and fuck the rest. I guess in some twisted view a human nature. But I really have to severely twist it and leave any morals behind the door. Next time somebody will be praising US as some force of good in this world, well they can go fuck themselves too. /rant
  - deathgrips 6y ago
    Covid is not nearly as high on the priority list for many third world countries as it is for the US. Here covid shuts down everything. In many African countries it is an order of magnitude less impactful than malaria.
    - estaseuropano 6y ago
      There's less testing, less reporting and much less transparency and awareness. Doesn't mean there's less infection or less dying.
      - gridder 6y ago
        There probably is (less infection) due to the more broad vaccines they receive compared to developed countries, which as a second effect create a little more broad immunity.
        ChrisIsTaken 6y ago
        Due to the much younger population, most of Africa, India, and Pakistan has had MMR, and it's been found that the mumps vaccine provides significant immunity. In the west most over 35 had measles only, or MR combination without mumps. DOI: 10.1128/mBio.02628-20 For some reason this hasn't been well covered in the media. I got an MMR booster in June based on preliminary findings, my GP thought I was insane.

mrtksn 6y ago

Chinese and the Russian vaccines were not even considered. Now those are used in mass vaccinations, soon EU would be behind all countries but those who barely have any government at all. People don't even want to talk about that, as if those alternatives don't exists. Non-EU countries in Europe are getting them. Serbia(6.1) and Turkey(2.3) are already close to EU average(2.6) or better on the vaccination process.

smnrchrds 6y ago
> EU would be behind all countries but those who barely have any government at all. Ouch. Reading this from Canada hurts. (We are way behind EU and I would be very surprised if we get ahead of them at any point).
- macromagnon 6y ago
  Canada has no large scale vaccine production capacity so even if they could license the production they couldn't produce any decent amount any time soon.
  - katbyte 6y ago
    I hope this is something that changes post pandemic.
    - macintux 6y ago
      I just hope there is a post-pandemic era. Too many unknowns still about the mutations and whether they’ll out-maneuver the vaccines.
      - maxerickson 6y ago
        Lots of reason for optimism. The vaccines can be retargeted, and like the flu vaccine, approved with a faster trial. And the mRNA vaccine production can continue to scale up. So if there is a need for a new vaccine, we can likely deploy it with a shorter interval to availability and much larger initial volume. We can also become more disciplined. We don't need to go all the way to a strictly enforced lock down to improve on the social distancing that we've done the last year (at least, not in the US). And we can try to get people to more widely accept contact tracing/tracking.

digikata 6y ago

I wonder why not cover younger people with the GSK version and older people with some other vaccine?

Throwawayaerlei 6y ago
Excellent question. Probably the biggest factor is that Phase III trials are insanely expensive, like a billion dollars plus or minus. High touch, 30,000 people minimum for the US, lasts two years, etc. Sanofi/GSK is hazarding some of their own money in this, and has to look at the market for COVID-19 vaccines, which is obviously weighted towards the elderly. Might also be risk management in wondering if the final results for the younger would be disappointing or worse, this problem with the elderly was learned through surrogate endpoints from serological as in blood testing of immune system responses. See Oxford for how they were led astray from their first big 500 Phase I/II people test of their vaccine platform, and achieved much worse results than they anticipated when put in the crucible of multiple Phase III trials and the real endpoints of getting COVID-19, or serious cases of it.
- sampo 6y ago
  > Phase III trials are insanely expensive, like a billion dollars plus or minus Do you have a source for that? JAMA Internal Medicine says a median of 19 million, but that's for all drugs, not specifically vaccines. https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2702287 https://jamanetwork.com/journals/jamainternalmedicine/articl...
  - Throwawayaerlei 6y ago
    Not a good or recent one, but reading the linked article indicates the sort of trials being done for vaccines will have a median much greater than the $19 million you cite. These trials enroll 30,000 subjects at minimum, and take 2 years, both of which substantially exceed the maximums cited in the paper that they or anyone else they knew of had tried. In the case of length, by 4 times. Thinking further, a billion is too high an estimate today, because these trials or one I looked closely at use smartphone "ediaries" to reduce the number of direct person to person contacts. But they're still high touch affairs, nothing substitutes for phone calls and direct examinations, although the latter are limited in number, but start with a general medical exam. Thanks for bringing that paper to my attention, I'll look more closely at it later.

neximo64 6y ago

You're saying this despite the weekly pcr and different efficacy testing methods?

Throwawayaerlei 6y ago
Can you be more specific? I'm happy to drill down to the individual Phase III trial protocols, but want to know which ones you're referring to. Plus I'm pretty sure I left myself a lot of wiggle room with efficacy claims like "very good" and "OK."
- neximo64 6y ago
  Some of the efficacy methods involved you saying you're sick and then getting tested (Pf/Mod). Others were you were swabbed weekly (thereby catching asymptomatic infections (AZ)). So the efficacy rates between the bunch aren't apples to apples comparisons. AZ has an understated efficacy rate, so it's better than 'OK'. It explains Jansens efficacy being broken down up to the number of hospitalisations (where it reduces nearly all of them)
  - Throwawayaerlei 6y ago
    AZ has an understated efficacy rate, so it's better than 'OK'. Maybe, but their and Oxford's testing has been such a mess, with more than one lie promulgated by AZ in public claims (the blended efficacy based on an appalling Oxford mistake that suggested a better dosing that later didn't pan out), that I don't have much confidence in their current Phase III claims. Which date back to early December and haven't been publicly updated. Those are based on 4 trials in different countries, less than 6,000 each for the official 21 day apart dosing and a 70% efficacy claim.

TheMechanist 6y ago

Gentlemen, the hole is due to the fact that no company has the large scale productive capacity for the newly discovered COVID-19 vaccine. Ordering earlier and paying more would just have shifted distribution around, and would not have made more doses available. Every vaccination done in the US or the UK means one less vaccine dose for Europe. And that is not "ducking responsibility", it is basic logic - as one cannot fit 10 pegs in 9 holes, one cannot vaccinate 10 people with 9 doses.

mauritzio 6y ago
Well the fact that the companies own the stuff that was researched with tax payer money, which then tax payer money must buy again also doesn't help to scale. As there is no real market but just an oligopol of producers. If the formulas would be public domain, the producers can compete who is fastest and there would be much more and they still earn good money...
anonuser123456 6y ago
Your model seems to assume a fixed production capacity? It would seem plausible that if you paid an extra billion or two, companies could find a way to scale up production faster.

thetis 6y ago

I just have been sollicitated to test the Janssen/Johnson and Johnson. Seems that it is still in Phase III in Western Europe. I'm not 100% sure to want to participate, split between: ok there is enough vaccine i'll be vaccinated in 3m OR OK i need to do this because we need more vaccines.

Throwawayaerlei 6y ago
Janssen has finished recruiting for their 1 dose Phase III trial, but is still doing that for their 2 doses 8 weeks apart trials, this huge one https://clinicaltrials.gov/ct2/show/NCT04614948 https://clinicaltrials.gov/ct2/show/NCT04614948 and this small one in the US and Belgium https://clinicaltrials.gov/ct2/show/NCT04436276 https://clinicaltrials.gov/ct2/show/NCT04436276 There reporting on their one dose trial's efficacy results is pretty good, about what I expected, so if this gets you that one first dose ASAP its seriously worth considering. It's also a relatively mature platform, used previously for their Ebola vaccine which passed an European Phase III trial, but wasn't the earlier one that made such a difference in the last outbreak. The other vaccines you might get are less mature platforms, AZ/Oxford 2 doses 21 days apart has less efficacy than Janssen's 1 dose (Oxford had not before 2020 ever tried testing their platform on more than 40 people at a time), the mRNA vaccines I'm sure you've heard all about, but I wouldn't make any bets on when Pfizer will be able to provide you a dose from their currently? closed Belgium plant.