On Friday, Pfizer announced results of their Phase II/III trial in children 6 months to under 5 years of age. There were two big wins and one massive set back: Wins: Vaccine was safe, so no severe events occurred. The vaccine dosage worked for kids between 6 months and under 2 years.
1) If the 6 mon- 2 yr trial was a success, why isn't Pfizer going to the FDA for approval on that now?
2) Wouldn't some protection be better than no protection? Why not get the 2-4 year olds started and then they could get a third dose when it is approved in the first half of the year? In the middle of the serge it seems two doses would provide some protection while they figure out the third dose, just the same as they did with the adults.
I’m just so sad. I’m so tempted to get my 4.5 year old vaccinated. I know lying isn’t the right move here but I am just so upset that we have to continue to live like this. I thought we might have a tiny shred of comfort coming relatively soon.
Purely a guess based upon what we know about vaccine design and how the pediatric immune system responds to different antigens:
* Immature immune systems don’t recognize antigens like adults until a child is at least two years old. Case in point: the polysaccharide antennae on the dozens of different serotypes of Strep pneumonia. Prevnar and Pneumovax target the same bug and those same antennae. But...
- The pediatric vaccine against Strep pneumonia (Prevnar) conjugates those antigens to a diphtheria protein to draw the attention of the immune system.
- In adults, we can just glop the different serotypes into a stable formula and trigger an immune response. Designing the adult vaccine (Pneumovax) was fairly straight forward compared to the pediatric version.
Sounds like the answer for a pediatric Covid vaccine (kids under 4) may be to present the spike protein to the immune system in a different way:
- Either conjugated to a protein (like Prevnar does)
- Or with an extra "adjuvant" chemical (like Tdap uses does) to trigger an immune response in the youngest children.
So obviously the 3 µg dosage was incorrect for 2- to under 5-year olds. But why wasn’t this detected in Phase I “dosage finding” stage? I don’t know. No one knows, because this data has not been publicly released or published. I have a bigger question, WHY isn't this data released, what else don't we know? Safety issues?
First, I think Andrew Saal might be on to something. A common error is to think there's no difference in the immune system as humans mature.
Second, I suspect the Phase 1 trial was under-powered, so they didn't really do the dose-determining statistical magic properly. Because Phase 1 trials are notoriously small, the age-range distribution could have been skewed enough to miss efficacy of dose in that group.
Would greatly appreciate your answers to these 3 questions: 1) What specific behavior(s) account for the high number of breakthrough cases among boosted adults who are already conscientiously following recommended safety protocols? 2) In terms of omicron's inherent transmissibility, what specific behaviors are leading to the increased transmission? 3)Should 'close contact' be redefined (e.g. no longer 15 minutes over 24 hours)? Thank you!
You do so much work for the good of everyone! Thank you for every second! You deserve to have your family safe, given all of your sacrifice. I’m so sorry for what must feel like a huge loss to you. I’m sure I’m not the only one wanting to console you for your grief! Huge comforting hugs!!
Any word on what is going on with Moderna’s pediatric Phase III trial? Given their more ‘aggressive’ approach you outline above, could we hear back from Moderna before Pfizer finishes this revised Phase III trial?
Your article is very well written and I admire your ability to blend compassion with critical analysis. But I do have a comment.
I object to you comment that the industry does not test the most vulnerable patients first.
In Covid-19, children are not the most vulnerable, unlike influenza.
More importantly, children are growing. Their metabolic pathways are not mature, as their metabolic and elimination organs are not typical of adults. The unexpected results of this trial underscore this point.
For these reasons we develop drugs in adults first, lest we inadvertently cause harm to children, not knowing the appropriate dosage. Imagine what would happen if a drug/vaccine caused adverse events in some pediatric subjects because we proceeded too aggressively, without understanding the nuances of development that resulted, for example, in the accumulation of a metabolic byproduct that does not occur in adults but does in children.
Thank you SO much for the info your giving us! I'm finding it really helpful to look back on some prior posts as my personal situation changes. Keep up this great service!
It's very frustrating and disappointing I agree. Thanks for the information. As it is, we keep changing our minds (or at least, the way we're "leaning") on our holiday travel plans too. The omicron news looks increasingly bad.
What's the status on trials for 6 months to 5 years for Moderna and J&J? Might one of those be able to leapfrog Pfizer now, and if so, when might we expect EUA or final approval?
Can anyone find any meaningful data on the risks of a higher vaccine dose for the 2-5 age group? I can’t find any data showing that the risk of a 10 microgram (or greater) vaccine is more dangerous than a child actually getting COVID. And COVID exposure feels imminent with omicron. Any thoughts on this or where to look for more info?
Trusting you will be celebrating this holidays and without any dramatic news we will not hear from you so I wish you a very HAPPY HOLIDAY to you and your family.
So helpful, thank you! Two questions:
1) If the 6 mon- 2 yr trial was a success, why isn't Pfizer going to the FDA for approval on that now?
2) Wouldn't some protection be better than no protection? Why not get the 2-4 year olds started and then they could get a third dose when it is approved in the first half of the year? In the middle of the serge it seems two doses would provide some protection while they figure out the third dose, just the same as they did with the adults.
I’m just so sad. I’m so tempted to get my 4.5 year old vaccinated. I know lying isn’t the right move here but I am just so upset that we have to continue to live like this. I thought we might have a tiny shred of comfort coming relatively soon.
Purely a guess based upon what we know about vaccine design and how the pediatric immune system responds to different antigens:
* Immature immune systems don’t recognize antigens like adults until a child is at least two years old. Case in point: the polysaccharide antennae on the dozens of different serotypes of Strep pneumonia. Prevnar and Pneumovax target the same bug and those same antennae. But...
- The pediatric vaccine against Strep pneumonia (Prevnar) conjugates those antigens to a diphtheria protein to draw the attention of the immune system.
- In adults, we can just glop the different serotypes into a stable formula and trigger an immune response. Designing the adult vaccine (Pneumovax) was fairly straight forward compared to the pediatric version.
Sounds like the answer for a pediatric Covid vaccine (kids under 4) may be to present the spike protein to the immune system in a different way:
- Either conjugated to a protein (like Prevnar does)
- Or with an extra "adjuvant" chemical (like Tdap uses does) to trigger an immune response in the youngest children.
So obviously the 3 µg dosage was incorrect for 2- to under 5-year olds. But why wasn’t this detected in Phase I “dosage finding” stage? I don’t know. No one knows, because this data has not been publicly released or published. I have a bigger question, WHY isn't this data released, what else don't we know? Safety issues?
First, I think Andrew Saal might be on to something. A common error is to think there's no difference in the immune system as humans mature.
Second, I suspect the Phase 1 trial was under-powered, so they didn't really do the dose-determining statistical magic properly. Because Phase 1 trials are notoriously small, the age-range distribution could have been skewed enough to miss efficacy of dose in that group.
Would greatly appreciate your answers to these 3 questions: 1) What specific behavior(s) account for the high number of breakthrough cases among boosted adults who are already conscientiously following recommended safety protocols? 2) In terms of omicron's inherent transmissibility, what specific behaviors are leading to the increased transmission? 3)Should 'close contact' be redefined (e.g. no longer 15 minutes over 24 hours)? Thank you!
You do so much work for the good of everyone! Thank you for every second! You deserve to have your family safe, given all of your sacrifice. I’m so sorry for what must feel like a huge loss to you. I’m sure I’m not the only one wanting to console you for your grief! Huge comforting hugs!!
Any word on what is going on with Moderna’s pediatric Phase III trial? Given their more ‘aggressive’ approach you outline above, could we hear back from Moderna before Pfizer finishes this revised Phase III trial?
Your article is very well written and I admire your ability to blend compassion with critical analysis. But I do have a comment.
I object to you comment that the industry does not test the most vulnerable patients first.
In Covid-19, children are not the most vulnerable, unlike influenza.
More importantly, children are growing. Their metabolic pathways are not mature, as their metabolic and elimination organs are not typical of adults. The unexpected results of this trial underscore this point.
For these reasons we develop drugs in adults first, lest we inadvertently cause harm to children, not knowing the appropriate dosage. Imagine what would happen if a drug/vaccine caused adverse events in some pediatric subjects because we proceeded too aggressively, without understanding the nuances of development that resulted, for example, in the accumulation of a metabolic byproduct that does not occur in adults but does in children.
No one wants to risk injuring a child.
Second: "Moderna is now facing the possibility of no authorization due to myocarditis concerns" Which age group, primary or booster?
Thank you SO much for the info your giving us! I'm finding it really helpful to look back on some prior posts as my personal situation changes. Keep up this great service!
It's very frustrating and disappointing I agree. Thanks for the information. As it is, we keep changing our minds (or at least, the way we're "leaning") on our holiday travel plans too. The omicron news looks increasingly bad.
What's the status on trials for 6 months to 5 years for Moderna and J&J? Might one of those be able to leapfrog Pfizer now, and if so, when might we expect EUA or final approval?
Can anyone find any meaningful data on the risks of a higher vaccine dose for the 2-5 age group? I can’t find any data showing that the risk of a 10 microgram (or greater) vaccine is more dangerous than a child actually getting COVID. And COVID exposure feels imminent with omicron. Any thoughts on this or where to look for more info?
Any idea yet if Pfizer will be doing a simultaneous trial with a higher dosage for 2-5?
Once again you knock it out of the park.
Trusting you will be celebrating this holidays and without any dramatic news we will not hear from you so I wish you a very HAPPY HOLIDAY to you and your family.