Paper and Threads

On Monday Oct 21st Pfizer had a press release about the efficacy of their 3rd dose.  They reported results from a randomized control trial -  on subjects from their Phase 3 Clinical Trial that all received 2 doses of the primary 2 dose series. More than 10, 000 volunteers from age 16 and older received 30 ug of the Pfizer BioNTech vaccine or placebo.  The median time between their second dose and the booster was 11 months.  Symptomatic covid-19 infections were assessed from at least 7 days after the booster or placebo with a median follow-up of 2.5 months.  There were 5 cases of Covid in the boosted subjects and 109 cases in the placebo group for a vaccine efficacy of 95.6%  None of the patients had evidence of a prior Covid infection. 

The age group had 55% subjects between 16 and 55 years and 23% of the subjects were were 65 and older.  They reported that after multiple subgroup analyses the efficacy was consistent across all of the age groups, sex, race, ethnicity and comorbidities.  That is excellent news for the group of 65+ subjects who all received their primary vaccination as part of the original trial and had an excellent immune response to the 3rd dose  now.  Pfizer says that the adverse event profile was the same as the original group and no safety concerns were found.  The Pfizer Press Release says that detailed results from this trial will be submitted to the FDA, European Medicines Agency and for a peer reviewed publication.  See Below  

This very preliminary report is real world data of the efficacy of the 3rd dose at a time when the delta variant was circulating and it makes me happy to see that age didn't affect the immune response or side effects.  In September the FDA and CDC approved the Pfizer 3rd dose going forward for people over the age of 65 and for younger people with a high risk of severe infection or risks of infection because of the groups with whom they are working.  The FDA and CDC recently analyzed a clinical trial of mixing and matching the type of booster with the original vaccine type, now that Moderna and J & J vaccine booster doses were also approved.  However they suggested that it was probably best to continue with the same vaccine type unless their were significant reasons to change.     

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Yesterday the FDA VRBPAC Advisory Committee approved the Pfizer Covid-19 vaccine for children 5-11 years old.  At least 1.8 million children in this age group have had Covid, 8622 have been hospitalized, and 143 have died.  The Pfizer vaccine dose for adults is 30ug, and a dose of 10ug was selected for each of the two doses 3 weeks apart in these children because it gives a comparable immunity at only 1/3rd the dose.  When developing vaccines for children scientists test smaller and smaller doses until they find one that produces the same antibody response and protection against infection as an older age group.  This dose produced the same antibody levels and protection against infection as was seen with 30ug in the 16-25 year old vaccine study. 

The initial Phase 3 clinical trial had 2288 subjects which were randomized 2:1 (vaccine:placebo). This group was followed for 3.3 months and the placebo group had 16 cases of Covid-19 and the vaccinated group had only 3 for a vaccine efficacy of 91%.  In order to carefully evaluate side effects the FDA required Pfizer to double the size of the study and that group had been followed for almost 3 weeks after their 2nd dose before this report. Very rare cases of mild myocarditis has occurred in old children and adults.  This was a side effect of both of the mRNA vaccines and onset usually occurred within 7 days of vaccination and resolved quickly with non-steroidal meds.  No cases of myocarditis were seen in either group of vaccinated children - most cases are seen in males between the ages of 16 and 39 - and very rarely in younger children.   See Below  

The side effects of vaccination in the clinical trial included mild to moderate pain, redness, and swelling at the injection site and fever, fatigue, headache and chills which were less frequent than in the 16-25 year old comparative clinical trial group.  No myocarditis or other serious adverse effects were seen.  There are several large safety systems in place to monitor side effects of all vaccine and drug clinical trials and any early warning signs are followed very closely by the FDA and CDC.  The benefit vs risk ratio is calculated for every drug or vaccine and the scientific advisory committees carefully examine all possible risks and felt that the benefits of this vaccine in 5-11 year old children far outweighs the risks.  The CDC ACIP Advisory Committee will meet Nov 2-3 and again review the vaccine data.  If approved the CDC Director then will give the final approval and vaccinations can begin.   

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Last week the FDA VRBPAC scientific advisory committee met and approved both the Moderna and Johnson & Johnson vaccine booster doses. The CDC then met this Thursday and spent the entire day listening to presentations by the companies and many CDC scientists who independently reviewed the data submitted by each company.  After a full day of analyzing and considering the efficacy and safety of the proposed booster doses, there was unanimous approval of both vaccine boosters.  Final approval was granted by Rochelle Walensky, Director of the CDC. 

The Moderna booster is one half the dose of the original two doses - 50ug instead of 100ug.  This dose had vaccine efficacy that was the same as the original vaccination dose and no increased symptoms following the injection. The booster doses were approved for the same group as the Pfizer booster: people 65 yrs or older at least 6 months after their 2nd dose, individuals 18-64 years of age at high risk of severe Covid-19, and individuals whose frequent institutional or occupational exposure to SARS-CoV-2 puts them at higher risk of serious complications of Covid-19.  The J & J vaccine was approved as a 2nd dose, to be given more than 2 months after the initial dose for all age groups.     See Below  

The Committee also reviewed all of the data from the NIH  "Mix and Match Vaccine Study" that was just reviewed here on my blog earlier this week, and they approved all 3 vaccines for the booster doses.   That means that each patient can select the booster dose type that they want, based on availability, or personal preference.  The Mix and Match study demonstrated that all of the heterologous and homologous booster doses produced a good immunologic response - and getting a second vaccine type was safe. 

The only way that this pandemic will be controlled is through vaccination of most of our citizens.  We are very lucky that we have very effective vaccines - please get a vaccination if you are still one of the unvaccinated.  Next week I'm looking forward to following the full day FDA meeting about the vaccine for children age 5-11.  The CDC meeting for these vaccinations is in the first week of November.

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The NIH NIAID reported preliminary results from an ongoing study of mixed and matched booster doses.  There were 458 subjects in 3 primary groups.  One group was vaccinated with Moderna (2 doses), one received Pfizer (2 doses) and the 3rd one received J and J (one dose).  At least twelve weeks after their primary vaccination, and without any history of a Covid-19 infection, each of the 3 groups were further divided into 3 groups (about 50 each) and those groups each received a booster dose- either Moderna, Pfizer, or J and J.  Thus there were 9 final groups.  For example, the group vaccinated with Moderna could have been boosted with Moderna at half the original dose (homologous), or Pfizer (heterologous). or J and  J (heterologous).

See Below  

Preliminary Results:  There was an anamnestic antibody response with all of the boosters, but the study wasn't set up to compare the antibody and neutralizing antibody titers among groups.  In addition, the cellular component of an immune response (memory B cells and T cells) is being analyzed, but is not yet complete. 

But there were no differences between the reactogenicity, local and systemic symptoms, in the heterologous vs the homologous booster doses and most were mild. Knowing that the mixing of vaccines is safe makes this a possibility moving forward.  There are many ways that this will make the booster dose easier to deliver:  patients who may have had an allergic reaction to one of the vaccines can be given one of the others.  It also will make it easier to go into a congregant care facility and boost all patients with just one vaccine type.  The FDA and CDC will now have to analyze and approve this plan to mix and match!  Stay tuned for the final approval and ongoing booster plans to be determined by the CDC and their scientific advisory committee.

Posted by Shirley at 5:45 AM | Permalink | Comments (0)

On Thursday the FDA VRBPAC Advisory Committee met to review a request from Moderna for an EUA for a 3rd dose of the Moderna vaccine.  Moderna tested a 50 ug dose instead of 100ug which is used for the 2 dose vaccination.   There were scientific presentations most of the day, including one by the Moderna scientists, and one in which all of the data submitted by Moderna was reviewed by FDA scientists.  When the delta variant became the dominant and then the sole variant for SARS-CoV-2, the efficacy of the vaccines had to be reassessed - including the potential need for booster doses for fully vaccinated individuals. 

Moderna was requesting approval for 3rd doses at least 6 months after their 2nd dose: for 1. Individuals 65 years of age and older, 2. Individuals 18-64 years of age at high risk of severe Covid-19 and 3. individuals whose frequent institutional or occupational exposure to SARS-CoV-2 puts them at higher risk of serious complications of Covid-19 including severe Covid-19.  Data had to be presented that the 50 ug dose was as immunogenic and met the criteria for antibody production and safety, and much of the information presented was confirmation of both.  The 3rd dose in individuals who received the two dose vaccination schedule 4 weeks apart did not have any more symptoms than after they had received the 2nd dose - and no new safety signals were seen.  The advisory committee unanimously approved Moderna's application and now the CDC ACIP advisory committee will meet next week for additional scientific reviews and then vote on the EUA for a 3rd dose of Moderna for the outlined groups. See Below:  

The Moderna and Pfizer vaccines are still both very effective in younger groups, but there was concern that the 65+ aged adults were starting to show waning immunity against the delta variant.  They presented some data that convinced me that we older adults should receive a 3rd dose.  Moderna was able to study 2 groups of patients from their original 30,000 plus Clinical Trial - the group that initially received the vaccine (early group - median time since vaccination 13 months) and the people who were in the placebo group, but after approval of the vaccine in Dec. 2020 were vaccinated (late group - median time since vaccination 7.9mos).  There were significantly more breakthrough cases after the delta variant spread in the "early" group, than in the "later" group, including some severe cases.  This is real world evidence that the vaccine is still efficacious against the variants, but not as good in older adults who have a lower immune response than those less than 65 years.  Some virologists think it may be a "3 dose vaccine" in order to have long lasting immunity, but only time will tell.

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