Are vaccines the light at the end of the tunnel?

[npcl]

18 minutes ago, Homosassa said:

I was curious, so I looked up the package insert for one of the common childhood vaccines.

 

Transerse myelitis is a recognized adverse event (incident rate is less than 1 %) for the vaccine, but it is also a known problem with the viral disease itself.

 

 The stopping of the Covid 19 trial due to this occurrence of tranverse myelitis is the second time the trial was stopped. It was also stopped due to another incident of transverse myelitis in July. However, the patient in that occurrence had an diagnosed case of MS.

My under standing is that as of yet, while there have been some cases show both in clinical trials and in vaccine monitoring the statistics do not indicate a causal effect with existing vaccines. Unlike the the 1976 flu and EBS where the number of cases developing within a 6 week period was twice the expected rate.

 

I assume  that in the  insert it was just lumped  in the less than 1% category and no actual statistic presented.  

 

2 cases in the study population of this size would certainly be unexpected.

Edited September 9, 2020 by npcl

[Homosassa]

1 hour ago, npcl said:

 

 

2 cases in the study population of this size would certainly be unexpected.

Yes, but the first case was probably associated with the MS, not the vaccine.  

 

I have no idea on the length of time between the vaccine and the appearance of thee transverse myelitis in the second case.

I had my flu shot last week so I looked at the information statement given out with the vaccine. It mentions Guillain-Barre Syndrome  as a risk. 

[npcl]

31 minutes ago, Homosassa said:

Yes, but the first case was probably associated with the MS, not the vaccine.  

 

I have no idea on the length of time between the vaccine and the appearance of thee transverse myelitis in the second case.

I had my flu shot last week so I looked at the information statement given out with the vaccine. It mentions Guillain-Barre Syndrome  as a risk. 

However even with MS the risk for Transverse myelitis only increases from 5 cases per million to  25 cases per million. So if both case do turn out to be Transverse myelitis the numbers are not good.

 

AstraZeneca is saying that the diagnosis has not been confirmed as of yet.

 

They do list GBS with flu at about 1 case per million, but the rate is less than GBS in those that have gotten the flu and far less than the normal incidence for GBS (12 -30 per million per year).  Because there were two studies that seemed to indicate a relationship they list it, but more studies have indicated that there is not one.

Edited September 9, 2020 by npcl

[markeb]

56 minutes ago, npcl said:

However even with MS the risk for Transverse myelitis only increases from 5 cases per million to  25 cases per million. So if both case do turn out to be Transverse myelitis the numbers are not good.

 

AstraZeneca is saying that the diagnosis has not been confirmed as of yet.

 

They do list GBS with flu at about 1 case per million, but the rate is less than GBS in those that have gotten the flu and far less than the normal incidence for GBS (12 -30 per million per year).  Because there were two studies that seemed to indicate a relationship they list it, but more studies have indicated that there is not one.

 

Vector related? It's an incompetent virus, but...

 

The numbers sound miniscule, but they're less than miniscule in the general population. I think you've posted over and over that one of the purposes of a large scale Phase III is to identify safety concerns. And there are no approved human vaccines using an adenovirus vector. Burden of proof is and should be very high.

 

If they don't get more cases, and show good protection, I'll be cautiously optimistic. But if this is the diagnosis, and they potentially have 2 cases in less than 30K where 5 cases in a million is expected, forget about speed; accuracy just became really important!

 

(One nice thing about living close to the Beltway is that the WP and the local affiliates have NIAID on speed dial; one of the local anchors sees Dr. F in her neighborhood regularly. I think his response was cautious concern, but we need data...)

[Homosassa]

Because I was around in 1976 and had to take the swine flu vaccine (essential personnel) when it became available, I remember when the GBS started showing up in the recipients of the vaccine.

 

The teenage daughter of one of my mother's coworkers also died from GBS after getting the swine flu shot.

 

I know the incidence rate is infinitesimally small, but it is just something that made an impression. 

[npcl]

12 minutes ago, markeb said:

 

Vector related? It's an incompetent virus, but...

 

The numbers sound miniscule, but they're less than miniscule in the general population. I think you've posted over and over that one of the purposes of a large scale Phase III is to identify safety concerns. And there are no approved human vaccines using an adenovirus vector. Burden of proof is and should be very high.

 

If they don't get more cases, and show good protection, I'll be cautiously optimistic. But if this is the diagnosis, and they potentially have 2 cases in less than 30K where 5 cases in a million is expected, forget about speed; accuracy just became really important!

 

(One nice thing about living close to the Beltway is that the WP and the local affiliates have NIAID on speed dial; one of the local anchors sees Dr. F in her neighborhood regularly. I think his response was cautious concern, but we need data...)

I agree, 2 cases in a trial with less than 30,000 enrolled is certainly a major red flag, even if one was MS related.

[npcl]

12 minutes ago, Homosassa said:

Because I was around in 1976 and had to take the swine flu vaccine (essential personnel) when it became available, I remember when the GBS started showing up in the recipients of the vaccine.

 

The teenage daughter of one of my mother's coworkers also died from GBS after getting the swine flu shot.

 

I know the incidence rate is infinitesimally small, but it is just something that made an impression. 

That is why you look at even the smallest of numbers looking for a causal effect.

[gerelmx]

AstraZeneca reported that a woman in the UK had symptoms consistent with a rare but serious inflammatory spinal disorder.
The disease with which the symptoms were linked is called myelitis, but the woman's diagnosis has not yet been confirmed.
The trials were also stopped in July, after one patient also developed neurological symptoms, however, she was diagnosed with multiple sclerosis, which was not linked to the vaccine.
Clinical trials will resume next week.

[TeeRick]

Here is a fact sheet.

https://www.ninds.nih.gov/disorders/patient-caregiver-education/fact-sheets/transverse-myelitis-fact-sheet

 

This condition in rare instances could be caused by infections - viral or bacterial.  Many other causes too.  Immunological condition.   It could be caused in rare cases from a live viral attenuated vaccine which would mimic parts of a live viral infection.  Or possibly from a vaccine (any) administration that results in a heightened immune response - which might rarely lead to this event in some unfortunate subjects.  The chimpanzee adenovector used in the AZ trial is not replicating and is not a live attenuated virus approach.  But it is an untried approach in humans that requires cautious safety monitoring.  There should be a lot of focus and expertise applied right now to get this resolved and get the trial off the "pause" so second doses are not affected.  If the trial does resume and then another case is documented that will IMO kill this approach.

[TeeRick]

In my past I was involved in the Rotavirus vaccine efforts.  Why bring that up here?  Rotavirus is another RNA virus particularly deadly in kids and particularly in less developed countries.  The first vaccine licensed (RotaShield) was a live attenuated virus which was the rhesus monkey version.  After it was approved and in a large population it was found to cause a condition in infants called intussusception.   Alternative vaccines were later developed and approved (Rotarix, Rotateq) that were based on a human rotavirus attenuated virus.  No adverse intussusception.  So there could be differences using a chimpanzee adenovector approach (AZ/Oxford) vs a human adenovector approach (J&J) in terms of safety profile.  We are primates but most of us are not monkeys!😀

 

https://www.who.int/vaccine_safety/initiative/tools/Rotavirus_vaccine__rates_information_sheet.pdf?ua=1

Edited September 10, 2020 by TeeRick

[mimbecky]

On 9/9/2020 at 5:50 AM, TeeRick said:

2a) If related to vaccine - was it caused by the SARS-CoV-2 antigen expressed (this would not be a good outcome for all vaccines being developed using that same antigen, ie, SPIKE).

2b) If related to vaccine - was it caused by the technology (adenovector approach)?

 

How would they ever figure out the probability of either of these?

M

[TeeRick]

8 minutes ago, mimbecky said:

 

How would they ever figure out the probability of either of these?

M

It would take a very long time no doubt.  If it is related to the antigen (SPIKE) then this would probably happen in multiple approaches based on this antigen.  If it is the adeno vector (related to chimpanzee adeno) then it might not happen in the human adeno vector approaches.   But a lot of time and subjects will be required if this event is rare.  So not likely to figure it out quickly if at all.  They will just stop the trial if more of these events occur and hope that they are not present in other trials and approaches.

[markeb]

3 minutes ago, TeeRick said:

It would take a very long time no doubt.  If it is related to the antigen (SPIKE) then this would probably happen in multiple approaches based on this antigen.  If it is the adeno vector (related to chimpanzee adeno) then it might not happen in the human adeno vector approaches.   But a lot of time and subjects will be required if this event is rare.  So not likely to figure it out quickly if at all.  They will just stop the trial if more of these events occur and hope that they are not present in other trials and approaches.

 

That's what I was thinking. If it's the SPIKE, you're going to see it in all the approaches. If it's the vector, you shouldn't see it in other approaches. And if the subject has titers to dozens of viruses (which they'll now probably check), it'll take a long time. (Or to use a bad analogy, they just spun out in pit row...)

 

Fingers crossed on subunit candidates, but I think they're still running behind on trials. Haven't looked lately.

[npcl]

2 hours ago, markeb said:

 

That's what I was thinking. If it's the SPIKE, you're going to see it in all the approaches. If it's the vector, you shouldn't see it in other approaches. And if the subject has titers to dozens of viruses (which they'll now probably check), it'll take a long time. (Or to use a bad analogy, they just spun out in pit row...)

 

Fingers crossed on subunit candidates, but I think they're still running behind on trials. Haven't looked lately.

This does make me wonder a bit about Moderna's announcement that they were slowing their trial patient accruals (announced reason was to increase diversity).  Unlike the others, Moderna appears to be primarily running their own trials (though using NIH clinical networks) and has a lot riding on these trials.  For companies like J&J, Pfizer, AstraZeneca not so much.

 

Probably nothing, but it does make me curious.

[Arizona Wildcat]

3 hours ago, npcl said:

This does make me wonder a bit about Moderna's announcement that they were slowing their trial patient accruals (announced reason was to increase diversity).  Unlike the others, Moderna appears to be primarily running their own trials (though using NIH clinical networks) and has a lot riding on these trials.  For companies like J&J, Pfizer, AstraZeneca not so much.

 

Probably nothing, but it does make me curious.

Moderna stated the reason very clearly.  In Arizona their panel is under represented with minorities, especially those with undeying conditions.  I volunteered.  Was told if I was Native American, Hispanic or black they could use me.

Initially a vaccine probably worth a few billion.  Much of trail costs have been picked up by governments around the world.  Longer term vaccines have historically not been huge money makers as pharma Has always donated huge numbers of doses to poor countries.

[npcl]

38 minutes ago, Arizona Wildcat said:

Moderna stated the reason very clearly.  In Arizona their panel is under represented with minorities, especially those with undeying conditions.  I volunteered.  Was told if I was Native American, Hispanic or black they could use me.

Initially a vaccine probably worth a few billion.  Much of trail costs have been picked up by governments around the world.  Longer term vaccines have historically not been huge money makers as pharma Has always donated huge numbers of doses to poor countries.

During my 20 years in the industry I have seen a lot of things clearly stated publicly, while there was more to the story privately. That would not mean that the patient recruitment was not true, only that it might not be the whole story.

 

For the big PhRMA companies (and the non-profits working on vaccines) I would agree concerning vaccines.  As far as Moderna it is a biotech with no approved products and only its COVID vaccine in phase III.  As such it economic future is pretty much tied to this vaccine, not only for its potential revenue, but also to demonstrate its technology.

 

It also has made a couple of missteps early on with the way it announced some early results, just before doing a new stock offering, that certainly was controversial  in the industry (both pharmaceutical and financial). The management has certainly done it share of selling of stock since the COVID outbreak started.

 

Personally I tend to trust Pfizer and J&J more than Oxford and Moderna.  Oxford, at least, is having AstraZeneca run it trials.  While Moderna is using its own staff. Would have preferred if they had partnered with someone with a bit more experience in getting drugs completely through the process.

 

In general because of the economics Biotech firms are much more likely to push a product, that a big PhRMA company would kill off as being to high risk. For example, Pfizer, with its biotech partner  had 4 different phase 1 vaccines, took two into phase one, and then took one (better side effect profile into phase 3).  They have also been working on a second generation vaccine that should be going into phase 1 in the next month or two.

Edited September 10, 2020 by npcl

[npcl]

9 minutes ago, BOLOCRUISE said:

No.  Seasonal Flu shots are highly ineffective.  A rushed vaccine for a virus supposedly worse than seasonal flu?  No thanks.  I have never received a flue ***** and will not be forced to receive a COVID-19 vaccine.

 

You might not be cruising for a while them if the cruise lines require them.

 

The flu shots are actually highly effective against the selected strains that are included.  Their effectiveness is largely driven by how that selection compares to the number of different strains actually circulating in a given year.

[mayleeman]

1 hour ago, npcl said:

The flu shots are actually highly effective against the selected strains that are included. 

 

And, of course, any vaccine dose is 100% ineffective for people refusing to take it!

[phoenix_dream]

1 hour ago, BOLOCRUISE said:

No.  Seasonal Flu shots are highly ineffective.  A rushed vaccine for a virus supposedly worse than seasonal flu?  No thanks.  I have never received a flue shot and will not be forced to receive a COVID-19 vaccine.

 

If you want to cruise you may have to.  

 

Seasonal flu shots are not "highly ineffective".  No, they are not 100% effective, but also consider that if you do get the flu after getting a shot you will likely get a much lighter case than had you got nothing.  Additionally, there are people who cannot get flu shots for various medical reasons, including newborn babies.  If nothing else, when you get the shot you are reducing your risk of infecting more vulnerable people - much like wearing a mask!  This year above all others, it is an expression of consideration for others as much as it is protection of yourself.   If Covid peaks, it will be absolutely critical for the hospitals to be void of unnecessary flu cases.   I would hope that people who normally skip the flu shots be thoughtful of others this year and bite the bullet and do it.

[Arizona Wildcat]

1 hour ago, npcl said:

During my 20 years in the industry I have seen a lot of things clearly stated publicly, while there was more to the story privately. That would not mean that the patient recruitment was not true, only that it might not be the whole story.

 

For the big PhRMA companies (and the non-profits working on vaccines) I would agree concerning vaccines.  As far as Moderna it is a biotech with no approved products and only its COVID vaccine in phase III.  As such it economic future is pretty much tied to this vaccine, not only for its potential revenue, but also to demonstrate its technology.

 

It also has made a couple of missteps early on with the way it announced some early results, just before doing a new stock offering, that certainly was controversial  in the industry (both pharmaceutical and financial). The management has certainly done it share of selling of stock since the COVID outbreak started.

 

Personally I tend to trust Pfizer and J&J more than Oxford and Moderna.  Oxford, at least, is having AstraZeneca run it trials.  While Moderna is using its own staff. Would have preferred if they had partnered with someone with a bit more experience in getting drugs completely through the process.

 

In general because of the economics Biotech firms are much more likely to push a product, that a big PhRMA company would kill off as being to high risk. For example, Pfizer, with its biotech partner  had 4 different phase 1 vaccines, took two into phase one, and then took one (better side effect profile into phase 3).  They have also been working on a second generation vaccine that should be going into phase 1 in the next month or two.

 

1 hour ago, npcl said:

During my 20 years in the industry I have seen a lot of things clearly stated publicly, while there was more to the story privately. That would not mean that the patient recruitment was not true, only that it might not be the whole story.

 

For the big PhRMA companies (and the non-profits working on vaccines) I would agree concerning vaccines.  As far as Moderna it is a biotech with no approved products and only its COVID vaccine in phase III.  As such it economic future is pretty much tied to this vaccine, not only for its potential revenue, but also to demonstrate its technology.

 

It also has made a couple of missteps early on with the way it announced some early results, just before doing a new stock offering, that certainly was controversial  in the industry (both pharmaceutical and financial). The management has certainly done it share of selling of stock since the COVID outbreak started.

 

Personally I tend to trust Pfizer and J&J more than Oxford and Moderna.  Oxford, at least, is having AstraZeneca run it trials.  While Moderna is using its own staff. Would have preferred if they had partnered with someone with a bit more experience in getting drugs completely through the process.

 

In general because of the economics Biotech firms are much more likely to push a product, that a big PhRMA company would kill off as being to high risk. For example, Pfizer, with its biotech partner  had 4 different phase 1 vaccines, took two into phase one, and then took one (better side effect profile into phase 3).  They have also been working on a second generation vaccine that should be going into phase 1 in the next month or two.

Are the articles where Moderna stated it was partnering with NIH false?  All I think all of us want is a safe effective vaccine.  The political BS about pharma willing to rush a potentially unsafe or ineffective vaccine to market is pretty crazy.

Absolutely agree if a vaccine is not safe it will be killed.

Agree that if you do not want to leave the US, nobody is likely to require a COVID vax.  Many vaccinations are required to travel outside the US.  Sure seems likely proof of a COVID vaccination likely given the Worldwide situation.

We will see shortly when the cruise guidelines are published what will be required.

Also agree flu shots are just ok for effectiveness, but if it can reduce even by 10% people seeking care it will be worth it this year.

 

 

 

 

Edited September 10, 2020 by Arizona Wildcat

[markeb]

3 minutes ago, Arizona Wildcat said:

 

Are the articles where Moderna stated it was partnering with NIH false?  All I think all of us want is a safe effective vaccine.  The political BS about pharma willing to rush a potentially unsafe or ineffective vaccine to market is pretty crazy.

Absolutely agree if a vaccine is not safe it will be killed.

 

 

 

 

 

NIH isn't a vaccine developer either. It's a basic research institute with a lot of experience, but not in product development. I hadn't thought about it, but it is odd Moderna didn't partner with a company with a track record getting a vaccine through development.

 

In more normal times, I've seen biotechs largely get buzz and get bought out or merge. Going to market is a bit unusual for them.

 

And I agree, pharma can't rush an unproven product; too much on the line for them.

[npcl]

1 hour ago, Arizona Wildcat said:

 

Are the articles where Moderna stated it was partnering with NIH false?  All I think all of us want is a safe effective vaccine.  The political BS about pharma willing to rush a potentially unsafe or ineffective vaccine to market is pretty crazy.

Absolutely agree if a vaccine is not safe it will be killed.

Agree that if you do not want to leave the US, nobody is likely to require a COVID vax.  Many vaccinations are required to travel outside the US.  Sure seems likely proof of a COVID vaccination likely given the Worldwide situation.

We will see shortly when the cruise guidelines are published what will be required.

Also agree flu shots are just ok for effectiveness, but if it can reduce even by 10% people seeking care it will be worth it this year.

 

 

 

 

Moderna is using the NIH network, but the clinical trials are being run by their own clinical affairs and regulatory affairs staff which have not taken any product completely through the process. Compared to Oxford which is using AstraZeneca Clinical Affairs and Regulatory affairs staff.

 

Did not say anything about PhRMA or Biotech willing to take an unsafe or ineffective vaccine to market.  Only that smaller biotech companies are more willing to take a higher level of risk in taking products through the clinical trials process. If you are a big PhRMA company with 20 entities in your pipeline, knowing that only 10% of drugs that enter phase 1, will actually get approved you are much more likely to drop a product if there are any concerns, rather than take it through the vary expensive clinical trial process. For a new product for a large indication expect 2 billion plus on clinical trials and regulatory work.

 

That also applies to the economic considerations.  small biotech companies are more likely to take small market products through the development process, where as a big pharma company would consider them not worth the effort.

 

If you are a Biotech with 1 product you are more likely to continue development on that product, unless you run into something that clearly kills it.

 

It is one of the main reasons why Biotechs that have not taken a product through the complete process tend to partner with big Pharma companies to 1. validate their technology, 2. collect payments from the PhRMA company, 3. utilize the clinical and regulatory affairs expertise and resources. 

 

Now Moderna has partnered with AstraZeneca and Merck on other products starting a few years ago. However those products, even though the agreements were put in place a few years ago, are in earlier stages of development, nothing past phase 2.

Edited September 10, 2020 by npcl

[npcl]

1 hour ago, markeb said:

 

NIH isn't a vaccine developer either. It's a basic research institute with a lot of experience, but not in product development. I hadn't thought about it, but it is odd Moderna didn't partner with a company with a track record getting a vaccine through development.

 

In more normal times, I've seen biotechs largely get buzz and get bought out or merge. Going to market is a bit unusual for them.

 

And I agree, pharma can't rush an unproven product; too much on the line for them.

I spent a number of years on the senior management team of a biotech.  While we did license out technology  and have several partnerships with big pharma companies, we did take 4 products through the development process to registration (4 out of 4 that we took into clinical trials).  The market for those products were all small oncology indications.

 

 

Edited September 10, 2020 by npcl

[Arizona Wildcat]

I would assume NIH can properly staff a multi site phase 3 trial.

The cruise lines had their meeting today with the CDC.  No idea what was said except CLIA will provide a proposal to the CDC on how to resume cruising in about 10 days.

The media article on Cruise Hive seemed mostly concerned with the economic cost to the CLIA members. Hmmmm.

Guess we will see in a few weeks how things will look in the future and probably a good idea of when.

[Ken the cruiser]

1 hour ago, Arizona Wildcat said:

I would assume NIH can properly staff a multi site phase 3 trial.

The cruise lines had their meeting today with the CDC.  No idea what was said except CLIA will provide a proposal to the CDC on how to resume cruising in about 10 days.

The media article on Cruise Hive seemed mostly concerned with the economic cost to the CLIA members. Hmmmm.

Guess we will see in a few weeks how things will look in the future and probably a good idea of when.

I believe this is the Cruise Hive article you're referring to.

 

https://www.cruisehive.com/cruise-line-ceo-says-the-cruise-industry-is-close-to-devastation-in-miami-dade-meeting/41620