Paper and Threads

On Dec 10th the Vaccine and Related Biologic Products scientific Advisory Committee (VRBPAC) met virtually with the FDA Vaccine Group for 7 presentations and Q and A sessions.  Many FDA scientists analyzed hundreds of pages of data about the Pfizer BioNTech vaccine since Pfizer applied for an EUA in early November.  Their review was then summarized in a 53 page document which is available on the FDA site.  An Emergency Use Authorization (EUA) can be granted if there is a public health catastrophe and there is no licensed treatment.  There were more than 43,000 clinical subjects in the Pfizer Clinical Trial, half were vaccinated and half received saline placebo. The efficacy of the vaccine was 95% in both sexes, all ages, and racial/ethnic groups, and it appears as if an immune response appeared as early as day 12 after the first dose.  The major safety issues occur in the first 1-2 days after the vaccine injection and include flu-like symptoms that are mild to moderate.  Four vaccinated volunteers developed a Bell's palsy, but it is unclear that this is a higher incidence than in the general population.  When study subjects have been followed for 6 months, the EUA could be converted to a Biologic License Approval based on reassessment of the data. 

It is very comforting to see how many academic scientists have analyzed all of the data - both the advisory committee members and as career scientists at the FDA.  There are still limitations fo this vaccine - pregnant women and children younger than 16 have not been included in the clinical trials and now need to be tested separately.   Read Below. 

Two nurses had an acute allergic reaction on the first day of the vaccinations in the UK.  Both had a history of severe allergies and carried an EpiPen.   These reactions could be due to allergies to food, drugs, or vaccines and Pfizer is collecting as much information about them as possible.  It is comforting to know that severe food allergies, like peanuts and eggs, did not disqualify people from being part of the clinical trial and no allergic reactions were seen.  For now, they are recommending that anyone with severe allergies delay their injections until all of the information is assessed.  Both women were treated and recovered completely - at least one of them with epi-pen and steroids, but not disclosed for the other one.  

Posted by Shirley at 6:50 AM | Permalink | Comments (1)

There are new CDC guidelines for quarantine after a Covid-19 exposure.  They used information from studies which looked at when patients became symptomatic after exposure, and the duration of virus shedding, after a known exposure and infection. The risk of passing along an infection will still be low (but not non-existent), if people have to return to work.  For those that can stay at home, 14 days is still a good plan.  Here are the two new options:

1.  Those without symptoms after exposure may return to normal activities (if asymptomatic) after ten days.  

2.  Those without symptoms, and a negative test (done before the end of their quarantine period), may resume normal activities after 7 days.

All public health measures should still be followed: mask,  social distancing, and hand washing.  Read Below: 

I plan to watch the FDA Pfizer Vaccine Committee Hearing on Thursday (9-6), and hopefully will be able to add lots to the information we already have.  There is a full report from the data analysis on the website (greater than 50 pages of data and tables) and the meeting agenda.  In addition, there may be more info on when we can get more Pfizer vaccine since our government only ordered one batch and contracts were signed with many other countries in the interim.  The US will probably have to wait until next summer for more, after we get the 100 million doses from the original contract that was signed.  These reports re: the US not ordering more when offered during the summer are in multiple newspapers and press releases as of this week.

Posted by Shirley at 7:36 AM | Permalink | Comments (0)

Demand for vaccinations will exceed supply until the first quarter of next year.  In preparation for vaccinating the population, the National Institute of Sciences, Engineering, and Medicine established a scientific advisory group to develop a distribution plan for consideration by the CDC.   

The CDC Advisory Committee on Immunization Practices (ACIP), an independent scientific advisory board, met on Dec 1st, to discuss these recommendations and approve a plan to begin vaccinations as soon as the Pfizer and Moderna vaccines receive an Emergency Use Authorization (EUA) from the FDA.  I listened to the presentations and discussion, and at the end of the meeting the ACIP recommended that health care workers and staff and residents in long term care facilities (LTCF) should be vaccinated in Phase 1a.  After the CDC Commissioner approves the plan the vaccines will quickly be disseminated to States and Territories based on their adult populations.  Each State will be in charge of the developing the system to vaccinate the selected groups.  

Read below:   

Data Presented:  There were 245,000 infections and 858 deaths in Health Care Workers at the time of their deliberations.   Patients in LTCF accounted for 6% of cases (approximately500,000) and 40% of deaths (70,000).  The ACIP discussed sub-priorities in each group based on their actual risks, and even wanted the workers in facilities to be vaccinated on a schedule that wouldn't effect their daily work force if immediate symptoms from the vaccine kept them home for a day.  Approximately 40 million doses, which will vaccinate 20 million people, may get the vaccines before the end of the year.

Still to be discussed, Phase 1b will probably essential workers (police, fireman, bus drivers, train conductors etc) and Phase 1c may be adults over the age of 65 and people with high risk co-morbidities.  I assume these decisions will be presented and discussed at subsequent ACIP meetings like the one I watched this week. 

Posted by Shirley at 6:07 AM | Permalink | Comments (0)

Monday Moderna released the next batch of data from their phase 3 Vaccine trial that they conducted with the NIH-NIAID.  When they reached a total of 196 Covid-19 cases (out of 30,000 volunteers) the Data Safety and Monitoring Board were allowed to determine how many cases were in the placebo group (185) and how many in the vaccine group (11), a 94% efficacy preventing Covid-19.  When they looked for the first time several weeks ago it was 94.5%.  There were no serious adverse effects- volunteers complained of pain and redness at the injection site, fatigue, muscle and joint aches, and headaches.  There were no serious adverse effects.

Of special note, there were 30 severe cases plus 1 death in the placebo group and none in the vaccine group.  Sometimes vaccinated patients develop worse infections after vaccination, called "vaccine enhancement."  None was seen with this vaccine. The vaccinated group will still be followed for a full 24 months to make sure there are no late side effects. 

The volunteers included 20% Hispanics, 10% blacks, 4% Asians and the efficacy and side effects were the same in all of the subgroups.  There were 33 volunteers over 65 in the Covid-19 group.  

Read Below 

Then Moderna filed an application to the FDA for Emergency Use Authorization.  On Dec 10th the Pfizer application will be reviewed by the VRBPAC, the FDA scientific advisory board.  It is hoped that the FDA VRBPAC will evaluate the Moderna application on Dec. 17th.  As soon as the FDA grants emergency approval, the CDC can approve the distribution of the vaccines.  There may be 40 million doses from both companies for 20 million people (2 doses) by the end of December.  The vaccinated groups of the Phase 3 trials for both vaccines will be completed and published in peer-reviewed medical journals, with much more data.  The FDA will then review the completed trials and make decisions re: Biologic License Applications for final approval. The placebo groups will probably be vaccinated soon, so they can now be protected. 

Posted by Shirley at 6:07 AM | Permalink | Comments (0)

Antibodies from Covid-19 infected patients are of 3 main types: 

1. Convalescent Plasma - donated by a recently recovered patient.

2. Hyperimmune Globulins -the above antibodies that have been partially concentrated and purified.

3.  Monoclonal Antibodies - like the Regeneron Cocktail (2 very specific manufactured antibodies to the spike protein) and the Lilly product which has one specific manufactured antibody.  These were previously discussed here and now both have an Emergency Use Authorization.  Randomized controlled Phase 3 clinical trials are in progress.

The effectiveness of infusing convalescent plasma was never proven because more than 60,000 Covid-19 patients were given without a randomized controlled trial (RCT).  Plasma could be given on a compassionate basis and observational studies are not sufficient to prove benefit.  This week the New England Journal of Medicine published a thorough RCT and proved that convalescent plasma was no better than placebo. 

Results published in New England Journal of Medicine Nov. 24, 2020:  228 patients were randomly assigned to receive convalescent plasma and 105 patients placebo.  The median time from symptoms to enrollment was 8 days, and low oxygen levels were the most frequent reason for the plasma.  Conclusion:  No significant differences were observed in clinical status or overall mortality at 30 days with convalescent plasma.  

https://www.nejm.org/doi/full/10.1056/NEJMoa2031304 

For More Information:  The Infectious Disease Society recommends that any patients receiving convalescent plasma should be enrolled in one of the ongoing randomized controlled clinical trials to gather as much data from RCT as possible. 

Published Nov 17, 2020 

https://www.idsociety.org/covid-19-real-time-learning-network/therapeutics-and-interventions/convalescent-plasma/ 

Posted by Shirley at 6:26 AM | Permalink | Comments (0)