Are vaccines the light at the end of the tunnel?

[deadzone1003]

20 minutes ago, nocl said:

Except AZ is not approved in the US, and depending upon the large US clinical trial may or may not be.  As such the AZ doses don't count at this time. 

 

No one (except for the Monitoring and Safety Board and they would only know what their last check would have indicated, not final numbers) knows what the J&J efficacy is, the trials has not yet been unblinded.

True to a certain degree except that we have paid for them already, J&J is expected to be approved next month or given a EUA at least if the early reports about the vaccine matches its final data.  AZ is expected to be approved in April.  This would give us a timeline of expected vaccines to be received.  Since the J&J vaccine is a viral vector vaccine like the AZ vaccine, it should be in the same ballpark.  To not recognize that these vaccines will probably be available would be silly.

[Ken the cruiser]

17 minutes ago, deadzone1003 said:

True to a certain degree except that we have paid for them already, J&J is expected to be approved next month or given a EUA at least if the early reports about the vaccine matches its final data.  AZ is expected to be approved in April.  This would give us a timeline of expected vaccines to be received.  Since the J&J vaccine is a viral vector vaccine like the AZ vaccine, it should be in the same ballpark.  To not recognize that these vaccines will probably be available would be silly.

That brings up an interesting question. With Pfizer and Moderna vaccines already flowing with an efficacy of around 95% and hopefully J&J has a high 80+% efficacy, will the AZ vaccine even be awarded an EUA if it's efficacy rate is shown to be in the 60-70% range?

Edited January 27, 2021 by Ken the cruiser

[markeb]

3 minutes ago, Ken the cruiser said:

That brings up an interesting question. With Pfizer and Moderna vaccines already flowing with an efficacy of around 95% and hopefully J&J has a high 80+% efficacy, will the AZ vaccine even be awarded an EUA if it's efficacy rate is shown to be in the 60-70% range?

 

A very good question. And there were early safety concerns. I don't think anyone knows, but that gets to the  heart of my "noninferiority" comment earlier.

 

We'll see. I really don't know, and I really wouldn't hazard a guess.

[nocl]

Just now, Ken the cruiser said:

That brings up an interesting question. With Pfizer and Moderna vaccines already flowing with an efficacy of around 95% and hopefully J&J has a high 80+% efficacy, will the AZ vaccinine even be awarded an EUA if it's efficacy rate is shown to be in the 60-70% range?

depends upon perceived benefit. if there is an adequate supply of more efficacious product, then probably not.

 

Assuming that the efficacy from the large US trial also comes in at 70%.

 

If the agency feels that there is an unmet medical need then it most likely would grant one. Atleast that was the criteria when I last worked there.

 

The key for an EUA is an unmet medical need that can be addressed with an acceptable level of risk.

 

Considering that the EU is beating AZ up over missed delivery dates and the need in other countries I could easily see the US letting go of its AZ orders if it is getting an adequate supply from other, more efficacious product.

[markeb]

3 minutes ago, nocl said:

depends upon perceived benefit. if there is an adequate supply of more efficacious product, then probably not.

 

Assuming that the efficacy from the large US trial also comes in at 70%.

 

If the agency feels that there is an unmet medical need then it most likely would grant one. Atleast that was the criteria when I last worked there.

 

The key for an EUA is an unmet medical need that can be addressed with an acceptable level of risk.

 

Considering that the EU is beating AZ up over missed delivery dates and the need in other countries I could easily see the US letting go of its AZ orders if it is getting an adequate supply from other, more efficacious product.

At the edges of my experience here. If the unmet need can be met by increased production of a product already under an EUA, and the applicant may have inferior performance? That may be where we’re heading with AZ unless its performance gets a lot better. 

 

[nocl]

1 hour ago, markeb said:

At the edges of my experience here. If the unmet need can be met by increased production of a product already under an EUA, and the applicant may have inferior performance? That may be where we’re heading with AZ unless its performance gets a lot better. 

 

I expect that AZ will only get an EUA if the Pfizer and Moderna can not deliver enough of their product soon enough.

[Crazy planning mom]

4 hours ago, nocl said:

I expect that AZ will only get an EUA if the Pfizer and Moderna can not deliver enough of their product soon enough.

Thank you for expert opinion.

[wrk2cruise]

I find it comforting that it may be possible to get enough vaccine for the entire population this year.  Has anyone taken into account that any surplus which I suspect wouldn't be available until very late this year may be required to start another round of booster doses?

[TeeRick]

12 hours ago, deadzone1003 said:

The freezers for the Pfizer vaccine is ultra-low, basically dry ice cold.  Who would even have a freezer that has to be at least -60 C cold?  Maybe a research hospital might have one or a very large medical center.  Rural areas are getting the Moderna right now.  I would be surprised if any got the Pfizer.  When I say the rural areas will get the J&J vaccine, it is more about Pfizer having to be used exclusively in Metropolitan areas.  This is just a common sense approach as you want to minimize the chance of spoilage.   

 

I understand about the ultralow requirements for the Pfizer vaccine.  But how much of a problem is this really for a country like the US pouring $billions into production and distribution of vaccines?  Sorry for being a bit facetious in my first response to you but I do not believe that access to ultralow freezers is that much of an issue except perhaps for local pharmacies.   Yes the Moderna vaccine and J&J vaccine if approved might be easier logistically for some very remote areas that have regular freezers.  Yes common sense I agree.  But Remote is different than Rural and Small Town which can be handled by regional medical centers.  Access to an available vaccine does not require any one-day emergency timing and can (and will) be scheduled days to weeks in advance.  So almost everybody can travel to the vaccine if they want it and if it not available in a short distance from their home.  

 

 

 

 

Edited January 27, 2021 by TeeRick

[nocl]

1 hour ago, TeeRick said:

 

I understand about the ultralow requirements for the Pfizer vaccine.  But how much of a problem is this really for a country like the US pouring $billions into production and distribution of vaccines?  Sorry for being a bit facetious in my first response to you but I do not believe that access to ultralow freezers is that much of an issue except perhaps for local pharmacies.   Yes the Moderna vaccine and J&J vaccine if approved might be easier logistically for some very remote areas that have regular freezers.  Yes common sense I agree.  But Remote is different than Rural and Small Town which can be handled by regional medical centers.  Access to an available vaccine does not require any one-day emergency timing and can (and will) be scheduled days to weeks in advance.  So almost everybody can travel to the vaccine if they want it and if it not available in a short distance from their home.  

 

 

 

 

Considering that we have entire industries running using just in time methods and that Pfizer has shippers that can keep the product for multiple days, it should not be that much of an issue in the US. It comes down to a scheduling problem. Making sure that sufficient appointments are scheduled to use the product within a day or two of receipt of the shipper. Should not be an issue in the early days when lots of people want the shots.

[TeeRick]

6 hours ago, nocl said:

I expect that AZ will only get an EUA if the Pfizer and Moderna can not deliver enough of their product soon enough.

This will depend entirely on the outcome of the US based phase 3 trial.  If dosing has been worked out to get similar efficacy to the other vaccines then I suspect an EUA will happen.  

[TeeRick]

2 hours ago, wrk2cruise said:

I find it comforting that it may be possible to get enough vaccine for the entire population this year.  Has anyone taken into account that any surplus which I suspect wouldn't be available until very late this year may be required to start another round of booster doses?

Yes if a booster is needed if immunity wanes to a point of needing it.  Time will tell.  But a  new vaccine  would be needed against a variant virus like the S.Africa strain.  

[TeeRick]

9 hours ago, deadzone1003 said:

True to a certain degree except that we have paid for them already, J&J is expected to be approved next month or given a EUA at least if the early reports about the vaccine matches its final data.  AZ is expected to be approved in April.  This would give us a timeline of expected vaccines to be received.  Since the J&J vaccine is a viral vector vaccine like the AZ vaccine, it should be in the same ballpark.  To not recognize that these vaccines will probably be available would be silly.

One key difference is that the AZ/Oxford vaccine uses a chimpanzee adeno vector and the J&J vaccine uses a human adeno vector.  There was one vaccine approved years ago for Rotavirus (called RotaShield) that used a Rhesus monkey version that ultimately needed to be recalled for a safety issue.  The human-bovine reassorted Rotavirus version (RotaTeq) and the human version (Rotarix) replaced it and these vaccines have been in use ever since that time.  The vaccine experts at the FDA definitely know this story.  There is no current evidence that the AZ chimp version suffers from safety issues but it will be a point of focus and discussion if there is an EUA meeting.

 

https://www.cdc.gov/mmwr/preview/mmwrhtml/mm4843a5.htm

 

https://www.cdc.gov/vaccines/vpd/rotavirus/hcp/index.html

[nocl]

2 hours ago, TeeRick said:

This will depend entirely on the outcome of the US based phase 3 trial.  If dosing has been worked out to get similar efficacy to the other vaccines then I suspect an EUA will happen.  

Considering that it only came to 70% by blending trials and the small trial with the half dose included no one over 55 the odds of that is slim. 

 

The US trial that the FDA is waiting for was the original dose and there does not seem to be any change in the trial docs on line. 

 

So not sure where any trials would be showing results for a different dosing scheme.

 

Of course with approval in the EU and the company under fire for delayed shipments a new trial is probably not a priority for them.

 

So yes if they can show similar efficacy they will probably get an EUA, but if they don't and Pfizer and Moderna deliver adequate supply than probably not. The odds of them showing equivalent efficacy is slim.

[deadzone1003]

I would think that the USA has sufficient vaccines to vaccinate virtually our entire population that is willing if the J&J comes through by middle of summer.  We will know in the next few weeks as J&J releases its data from its Phase III trials to get an EUA.  The question will be though it may not match the efficacy rate of the mRNA vaccines, will it be too low to offset it advantages of it being 1-dose and milder side effects?  Remember, so far all of the vaccines (excluding the Chinese vaccines which I have very little knowledge of) will result in less severity if you get sick with the virus.  One thing I am uncertain about, they are still testing the vaccines for children who has not reach puberty.  I would think the vaccine could be folded into the numbers in the 2nd Quarter orders.  If not, we have way more vaccines than we need even with just 3 vaccines (not including AZ).  When you think about it, if you are afraid of getting sick from the virus, get the mRNA vaccine.  If you are just afraid of dying or becoming a long hauler from the virus, get one of the approved vaccines. 

[D C]

12 hours ago, cangelmd said:

Maybe, maybe not entirely. Yes, there should be special outreach to disadvantaged populations and to people, African-Americans particularly who have history that makes then leery of some medical care, and to older folks of all races who may have difficulty getting out to a site. BUT, people who are resistant to vaccination or who have reduced access for whatever reason, are also protected by herd immunity generated by everyone else who gets a vaccine. Getting more people vaccinated buys time to reach out to those people who may have more issues with access or are simply afraid. It’s a balancing act.

What is happening in Israel is what should happen. There’s been a lot of conjecture in this thread about transmissibility and preventing infection and transmission vs just preventing disease. But while we don’t know for certain and won’t know until data from trials emerges, the most likely scenario has always been that you get people vaccinated with a vaccine with 95% efficacy for disease, hospitalization should go way, way down - the rate should fall off a cliff.  And not a minute too soon, because with the rate of transmission in the US, we are just a breeding ground for more mutation.

True, but the rate only declines if you vaccinate people who would have ended up in the hospital. 

The US approach is to define special groups of people and vaccinate them because those groups are special, even if only a tiny minority of the group is actually vulnerable. When 80 year olds are waiting to get on a list while 20-something pre-school teachers are going to the front of the line, it's going to take a while for the numbers to reflect the vaccine's helpfulness.
EVENTUALLY we'll get there. 

[D C]

3 hours ago, TeeRick said:

Yes if a booster is needed if immunity wanes to a point of needing it.  Time will tell.  But a  new vaccine  would be needed against a variant virus like the S.Africa strain.  

Which should be straightforward for the mRNA vaccines, right?  Is it more than programming the vaccine with instructions to "make this protein instead of that one"?

[deadzone1003]

15 minutes ago, D C said:

Which should be straightforward for the mRNA vaccines, right?  Is it more than programming the vaccine with instructions to "make this protein instead of that one"?

If they have the gene sequencing of the new variant, supposedly they could create a new vaccine over a weekend.  But, it is all the testing that they have to do in order to comply with US government regulations as well as world-wide regulations that takes much more time.  Total time it took the original mRNA vaccine was around 8 months, April-Dec?.  In that time will there be another mutation?  probably yes.  I guess that's the problem we will face until we, hopefully, reach herd immunity.  

[UnorigionalName]

27 minutes ago, D C said:

Which should be straightforward for the mRNA vaccines, right?  Is it more than programming the vaccine with instructions to "make this protein instead of that one"?

 

manufacturing it is trivial. The big question is what kind of study FDA will require for approval.   I think with talk of boosters and alternate strains we are kind of in uncharted territory. 

[TeeRick]

55 minutes ago, deadzone1003 said:

If they have the gene sequencing of the new variant, supposedly they could create a new vaccine over a weekend.  But, it is all the testing that they have to do in order to comply with US government regulations as well as world-wide regulations that takes much more time.  Total time it took the original mRNA vaccine was around 8 months, April-Dec?.  In that time will there be another mutation?  probably yes.  I guess that's the problem we will face until we, hopefully, reach herd immunity.  

The recent report is that Moderna is already creating the S.Africa variant vaccine which has a number of changes in SPIKE from the common infectious original strains.  It appears that the UK strain is more infectious but both Pfizer and Moderna have stated that their current vaccines will (should) be effective.    I would suspect Pfizer BioNTech to be working on S.Africa variant as well.  Creating the vaccine in the lab is very straightforward.  Probably already done I would guess.   It is the manufacturing and clinical testing that will take some time as stated by UnoriginalName.  And maybe in the future a combination mRNA mixed vaccine (original + S.Africa) in the same vial.   Other variants might emerge too but it takes a good number of mutations around SPIKE to evade the polyclonal AB response from the vaccine.  And even then you still have the protective T-cell response.

https://www.cnbc.com/2021/01/25/covid-vaccine-moderna-working-on-covid-booster-shots-for-south-african-strain.html

[Ken the cruiser]

Here is an interesting option the new administration is looking at with regards to the Defense Production Act.

 

White House exploring tapping drugmakers to produce rivals' vaccines (msn.com)

[deadzone1003]

27 minutes ago, Ken the cruiser said:

Here is an interesting option the new administration is looking at with regards to the Defense Production Act.

 

White House exploring tapping drugmakers to produce rivals' vaccines (msn.com)

I wonder what are the rules for other drugmakers to produce rivals' vaccines.  Do they have to go through another trial process?  If I was Moderna, I would demand complete control of the process else a goof-up by other drugmakers would damage its reputation.  At a minimum they would have to call it a Moderna generic.  How long does it take for another drugmaker to get up to speed?  3. 4 months?  I doubt anyone has the all of the required materials on hand to make the vaccine.  I just hope they are transparent about it when they do make their decision.  

[Arizona Wildcat]

3 hours ago, deadzone1003 said:

I wonder what are the rules for other drugmakers to produce rivals' vaccines.  Do they have to go through another trial process?  If I was Moderna, I would demand complete control of the process else a goof-up by other drugmakers would damage its reputation.  At a minimum they would have to call it a Moderna generic.  How long does it take for another drugmaker to get up to speed?  3. 4 months?  I doubt anyone has the all of the required materials on hand to make the vaccine.  I just hope they are transparent about it when they do make their decision.  

Within 3 or 4 months there should be plenty of vaccine.  Pfizer will be online with doubled+ capacity in Belgium.  And J&J or another will have vaccine approved.  The issue shortly will be syringes.  Already in short supply locally.  Merck making the Moderna vaccine - that is a stretch.

[nocl]

7 hours ago, deadzone1003 said:

If they have the gene sequencing of the new variant, supposedly they could create a new vaccine over a weekend.  But, it is all the testing that they have to do in order to comply with US government regulations as well as world-wide regulations that takes much more time.  Total time it took the original mRNA vaccine was around 8 months, April-Dec?.  In that time will there be another mutation?  probably yes.  I guess that's the problem we will face until we, hopefully, reach herd immunity.  

However, once they prove the technology (which to a large degree they have) and have gone through the full submission process it is likely that the agency will accept future booster versions based upon much quicker safety clinical trials, and antibody response, not requiring the large phase 3 trials that took a lot of the time.

[nocl]

4 hours ago, deadzone1003 said:

I wonder what are the rules for other drugmakers to produce rivals' vaccines.  Do they have to go through another trial process?  If I was Moderna, I would demand complete control of the process else a goof-up by other drugmakers would damage its reputation.  At a minimum they would have to call it a Moderna generic.  How long does it take for another drugmaker to get up to speed?  3. 4 months?  I doubt anyone has the all of the required materials on hand to make the vaccine.  I just hope they are transparent about it when they do make their decision.  

They would only have to demonstrate equivalence from the new facility.  Pretty easily done. Same process as when a manufacturer start production in another plant.

 

It would be a manufacturing contract between the original company and the company that will manufacture.  Same as if they decided to do it outside of the DPA.