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December 19, 2020

The Moderna Vaccine Application for EUA

The Moderna Vaccine, developed by the Massachusetts Company in collaboration with Dr. Fauci's Institute at NIH, was approved by the FDA last evening.

On Thursday I watched the FDA Vaccine Related Biologics Products Advisory Committee Meeting, during which 21 independent scientific committee members heard 2 presentations: (1) by Moderna with detailed information from their Phase 3 Clinical Trial (30,420 volunteers) and (2) the FDA who presented their summary by the more than 100 FDA Career Scientists' of the Moderna Trial data.  In order to approve a product with an Emergency Use Authorization (EUA) there needs to be a catastrophic public health emergency, and no licensed product to treat people.  The drug companies need to submit an enormous amount of data from their phase 3 clinical trials and after scientific review by independent committees and the FDA, approval can be granted if the benefits outweigh the risks.  The committee voted 20 to 0 to recommend an emergency use authorization (EUA), and the FDA usually follows their guidance.  There are many studies yet to be done to examine the immune response and duration, and virus transmission in infected subjects.  The FDA EUA was granted and the vaccine will be shipped.    See Below

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The Moderna efficacy in preventing symptomatic Covid-19 was 94% for different age, ethnic, and racial groups.  The vaccine also prevented severe covid-19 with 0 cases in the vaccine group and 30 in the placebo group. At least 50% of the enrolled volunteers were followed for more than 2 months and the side effects were almost all mild to moderate - with fever, pain, swelling, and redness at the injection site, headache, chills, fatigue, muscle and joint aches following the vaccination. Patients should be aware of these symptoms. Some of the same symptoms occurred in the placebo group at a lower incidence - which always surprises me! Symptoms increased after the second dose but were gone after several days.  There were 4 cases of Bell's palsy, in which the facial nerve, on one side of the face, is affected, but recovers slowly.  There was one case in the placebo group and 3 in the vaccinated group.  The incidence will be followed closely to see if turns out to be more frequent than the spontaneous incidence in the general population.  There were no allergy symptoms or anaphylaxis seen.  The vaccine needs to be stored at only -4 degrees C.and can be maintained in the refrigerator for 30 days - making it easier to transport and store.   

 

December 16, 2020

What is Operation Warp Speed?

When the coronavirus SARS-CoV-2 was identified last year scientists knew that vaccines needed to be developed and many companies and research facilities began the process (more than 150).  The fastest a vaccine has ever been developed is 4 years - the mumps vaccine.  Suddenly a pandemic was declared and a worldwide catastrophe was imminent.  By early April Dr. Peter Marks, an oncologist who worked in academia and the drug industry and was currently the head of the FDA division that regulates vaccines, began laying the groundwork for what would become Operation Warp Speed.  Working with Robert Kadlec he wrote a proposal for the HHS Sec'y Alex Azar for a process that went from screening potential vaccine candidates to distributing the final product to 330 million Americans. Dr.Marks was a longtime Star Trek Fan and dubbed the proposal Operation Warp Speed.   

They wanted to find 8 vaccines that were promising in early testing, and select 2 for each method of vaccine development.  The first 5 companies that were selected were Moderna, Oxford-AstraZeneca, Johnson and Johnson, Merck, and Sanofi Glaxo Smith Kline.  Pfizer didn't accept government funds for vaccine development, but signed a contract with the government to buy 100 million doses of their vaccine if successful.  Novavax and Vaxart were accepted later.  Operation Warp Speed was announced on May 15th and vaccine development became a private-public partnership with gov't financial support. Government funding also allowed the companies to begin manufacturing, which is a financial risk if the vaccines aren't successful.    Read Below  

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All drugs and vaccines go through preclinical, Phase 1, 2, and 3 Clinical Trials.  Phase 3 clinical trials randomize volunteers between vaccine and placebo to determine efficacy in preventing Covid-19 and safety.  In Operation Warp Speed, every company had to have 30,000-50,000 trial subjects to make sure that the results were statistically significant. Pfizer and Moderna had very successful Phase 3 Trials and both should have an Emergency Use Authorization within days.  Developing vaccines can be very frustrating and both Oxford-AstraZeneca and Sanofi-GSK have hit some problems.  Oxford-Astrazenca's trial inadvertently used half the amount of vaccine for the first dose in a portion of their trial participants (~3000), which actually showed higher efficacy than the 2 full dose vaccinations.  They now need to test these varying doses and add additional trial volunteers in order to determine if the efficacy continues to be 90%. Sanofi's vaccine was not as effective in older volunteers and the vaccine will be revised and retested in older subjects.  We should soon be hearing about clinical trials from the other 4, especially J and J and Merck.

 

December 12, 2020

The Pfizer BioNTech SARS-CoV-2 Vaccine Receives an EUA

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. 

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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.  

 

December 9, 2020

New CDC Guidelines for Quarantine After Covid-19 Exposure

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: 

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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.

December 5, 2020

CDC Recommendations for Vaccine Distribution

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:   

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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.