Paper and Threads

Distribution of the successful vaccines will be a huge challenge.  And the FDA must grant an Emergency Use Authorization (EUA) for each vaccine, when the application is filed by the company, before distribution can begin. The Pfizer application is first reviewed by an independent advisory group, the Vaccine and Related Biologic Products Advisory Committee (VRBPAC) on Dec. 10th.  Members of the committee are drawn from academia, research and clinical practice.  The hearings will be televised on Dec. 10th. 

The VRBPAC can recommend approval of the vaccine, or request more information from the company.  The FDA then makes a final decision, based on the advice from their FDA career scientists and the VRBPAC. 

Once approved, the vaccine distribution plans can begin.  The CDC is in charge of distribution and they have broad recommendations from the National Academies of Sciences, Engineering, and Medicine, who established 4 phases of vaccination beginning with health care workers.  The vaccines will be distributed directly to the states and territories.  The states then need to determine who and how they can immunize the first target group.  State governors have been complaining that they need funds to support the vast organization that will be needed for storage, personnel training, and scheduling the immunizations, and it is not clear that the current gov't is planning to release these additional funds as quickly as necessary.  It is a two dose vaccine and patients will need to be scheduled for the 2nd dose in 3 weeks - which requires careful planning, documentation. and availability of the 2nd dose.  The Pfizer vaccine needs to be maintained at -94 degrees Fahrenheit imposing additional limitations in each state until they each develop their own systems.   Some states are purchasing ultra-cold freezers for large storage and distribution sites, others will rely on dry ice pellets which the vaccine is packed in for shipment from Pfizer.  Read Below

This initial distribution will occur at a time when a new government administration is taking over, including state governors, and there is a surge in cases, and a record number of deaths.  Health care workers are already having difficulty with the increase in hospitalizations.  The US government may be given 20 million doses of the Pfizer vaccine in 2020, for 10 million health care workers (2 doses each) to be divided among the states and territories based on population.  We can only hope this phase of the Pfizer vaccine trial will go smoothly. 

I just scanned an Oct 30th 15 page CDC document of information re: vaccine distribution.  It was a series of answers to questions raised by the state governors and answered by the Dept. of Health and Human Services.  Each state was supposed to develop plans in October.

Posted by Shirley at 6:51 AM | Permalink | Comments (1)

Happy Dance for Pfizer Clinical Trial Results - It was 95% effective!!  There were no serious safety concerns. 

I was awake Wednesday morning when the email from Pfizer arrived in my inbox, just 2 days after Moderna's wonderful preliminary report -  what great news!  The independent Pfizer Data Safety and Monitoring Board (DSMB) broke the blinded study when the number of symptomatic, Covid-19 positive volunteers reached 170 cases.  The number rose quickly from their first look at 94 cases  because of the surge in new cases around the country.  Neither Pfizer, nor the volunteers, knew which group had the positive cases.  The DSMB is a group of scientists and statisticians who are allowed to look at the data at preset intervals.  The results showed that 162 of the infected patients were in the placebo group and 8 were in the vaccinated group, with 9 severe cases in the placebo group and 1 in the vaccinated group (new data since the 1st data review). And 94% of older patients were protected.  Vaccinated patients complained of fatigue and flu-like symptoms, but there were no reported serious adverse effects. 

With these results, Pfizer can now apply for Emergency Use Authorization for the vaccine in order to start vaccinating the placebo group and others.  Health care workers will probably be the 1st group - from the 25  million doses that will come to the US (2 shots per person 21 days apart).   The vaccinated patients will continue to be followed for a full 24 months in order to look for any late adverse effects.  The placebo group will probably be vaccinated as soon as the EUA is received.  Continue reading below.

Pfizer and Moderna vaccines were the first messengerRNA vaccines ever brought to this level, and their effectiveness is very impressive.    This vaccine development platform allowed the mRNA for a portion of the spike protein to be prepared very quickly by Moderna and NIH-National Institute of Allergy and Infections Diseases, with Dr. Tony Fauci as head.  NIH had been studying the coronaviruses for many years, and the spike protein of the virus was known to be the part of the virus which attaches to a receptor on human cells allowing the virus to infect mucosal cells in the nose, trachea and lungs.  

All of the vaccines under development are using techniques to isolate parts of the spike protein and to stimulate the immune system.  There are at least 4 categories of vaccine types, and the mRNA technique is just one of those - the newest.  The messengerRNA (a genetic pattern for a piece of the spike protein)  is prepared and injected into our muscles.  It enters our cells and acts as a template for them to make a small inactive piece of the spike protein.  Our cells then become a factory and as "spike protein" is made, it stimulates an immune response. I find it really fascinating!!

There will be much more information to come from the Pfizer and Moderna studies.  NIH will assess all parts of the immune response in the vaccinated volunteers, which will help scientists to understand the duration of immunity stimulated by the vaccine.  After the FDA receives the EUA application from Pfizer, the scientists appointed to an FDA board will review all of the data and make a decision.  It usually takes weeks for a decision, but the urgency for vaccine approval is such that it may be just a few weeks.  Then distribution can begin.  This will be a topic for another blog post.

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

Happy Dance #2 - Celebrating the preliminary information about the Moderna Vaccine.

I first heard of the National Institutes of Health NIAID/Moderna Vaccine in the Spring, just after the team had created the mRNA.  I was fascinated that a piece of messenger RNA could be made from the Sars-CoV-2 spike protein and injected into animals, and then humans to stimulate our own cells to make the spike protein, which could then turn on our immune response.  The preliminary announcement by Moderna on Monday was very exciting and I'm sure that everyone has heard that the efficacy was 94.5%.   Read Below 

All of the 30,000 volunteers are already enrolled in the clinical trial, and the Data Safety and Monitoring Board (DSMB) was allowed to open the blinded study when a specific number of volunteers had developed symptoms of Covid-19.  They did that last weekend and found that 95 volunteers were Covid-19 positive and 90 of them were in the placebo group.  Additionally 11 cases of severe Covid-19 were in the placebo group and none in the vaccinated group.  The reported adverse symptoms were fever, headache, arm pain, joint and muscle aches - and were transient after the 2 vaccine injections 28 days apart.  Volunteers: 37% of the enrolled group are people of color, 42% are high risk, with comorbidities or are 65+.

The DSMB will next look at the data after a total of approximately 150 cases of Covid-19 occur.  The FDA requires that every vaccine must be >50% effective to apply for FDA approval, and 50% of the volunteers must have been followed for at least 2 months after their second injection. Everyone hopes that it will still remain >90% effective with no cases of severe Covid-19 in the vaccinated group.  If approved, the Phase 3 Clinical Trial can be stopped at that point, although the vaccinated volunteers will be followed for a total of 24 months to make sure it is safe.

All of the data will be reviewed and analyzed, and then an FDA application for an Emergency Use Authorization can be filed.  Once it is approved, the placebo group will be vaccinated and production will be ramped up for distribution.  This mRNA vaccine, unlike the one from Pfizer, requires long term storage at -4 degrees F, but can be kept in a refrigerator for up to one month. 

Posted by Shirley at 6:00 AM | Permalink | Comments (0)

New York City residents went through a surge in March and April, when community spread from Europe was undetected because only symptomatic people who had traveled to China could be tested.  There weren't enough PPE and hospital workers had to reuse masks and gowns, if they could even get them.  Refrigerated trucks were a permanent mortuary downtown and auxiliary places were set up to receive patients because the hospitals and ICUs were full.  On March 20th a stay at home order was given for everyone except essential workers, and over the next weeks the infection rate dropped.  Huge testing programs were developed and initiated by the state and the daily % positive cases fell to below 1% for months and deaths to less than 20 most days.  Greater than 90% of people I passed on my daily early morning walk were wearing masks, and socially distancing.  Reopening was done by phases and the %positive virus cases remained low and steady.  Read Below.

A dashboard was established on the NY State website to follow the % positive virus tests and the number of deaths - by region, and even by zip code.  After such wonderful control of the infection last Spring and Summer, NY's cases and deaths are increasing very slowly.  Yesterday there were 11 hot spots in the state, and they are coded (red , orange, yellow from red =HOT) based on the infection rate and the restrictions that are imposed. Only 4 of them are now orange after restrictions were imposed, and the rest have returned to yellow.  On Thursday, 203,721 virus tests were done and the state, excluding the hot spots, had 2.3% positive tests and the hot spots had 4.6% positive cases.  The yellow zone still has some restriction, but of group size and shutdowns.  Last night new restrictions were established for the whole state - bars, restaurants, and gyms must close by 10PM and gatherings need to be limited to 10 or less people.  Public health measures really work as was demonstrated in Mar-May and I don't think any of us want to live through another surge.  Hopefully we New Yorkers will all continue to follow the state guidelines.  Banish pandemic fatigue!  44% of people my age were dying during the worst weeks last Spring.

Posted by Shirley at 7:30 AM | Permalink | Comments (1)

Why we should be happy and doing a dance?  The Pfizer and Moderna vaccines were made with a completely new process and no one knew whether it would be successful.  Messenger RNA for a portion of the virus spike protein was created and after injection the mRNA entered muscle cells stimulating them to make antibodies.  Several months ago the FDA created stringent guidelines for the vaccine companies to follow.  The Phase 3 trials are randomized controlled trials and everyone except the Data and Monitoring Safety Board (DMSB) know which volunteers were vaccinated and which received placebo.  The number of volunteers who developed symptoms and needed to have a +Covid test were predetermined and 62 was established as the first time the DMSB (Scientists independent of the study) could look at the data.  By the time the DMSB received, analyzed the data, and met on Sunday, there were actually 94 symptomatic and Covid-19 +cases, more than 90% of them in the placebo group.  The only other parameter reported was safety - and only minor reactions to the injections were found.  Read Below

The DMSB will next look at the data after there are 164 symptomatic and Covid-19 virus+ volunteers.  Then the trial will be unblinded and huge amounts of data will be studied.  A decision will then be made re: an application to the FDA for an Emergency Use Authorization.  Half of the volunteers need to be at least 2 months beyond their 2nd dose of vaccine.  And there must be at least 5 severe cases of Covid 19.  These are some of the requirements that the FDA established for all vaccine applications.

Some additional facts about this vaccine:

Pfizer and BioNTech, a German company, developed the vaccine.  The US did not contribute financially, (i.e it was not part of Operation Warp Speed). but the German Gov't did contribute millions.  The US has an agreement with Pfizer/BioNTech to purchase 100 million doses of the vaccine - that's it. If the efficacy and safety are as good after the 164th sick volunteer is counted, the placobo patients may be vaccinated, thereby ending the randomization.  Antibody production and T cell immunity still need to be assessed as part of the effectiveness assessment and the data from every 44,000 plus volunteer needs to reviewed  However the original vaccinated patients will be followed for a total of 24 months to assure there is no late vaccine side effect.  There will also a 4th Clinical trial - which is called "Post-Marketing" for everyone who subsequently received the vaccine.

Why should we do a happy dance?  It is exciting that the effectiveness is so high - proving the concept for an mRNA vaccine platform.  No one really knew whether this would work for either Moderna of Pfizer.  Secondly, the epidemiologists are predicting a Fall and Winter pandemic "from Hell" - i.e. the virus is already surging in the US, not rounding the corner.  High risk health care workers may be vaccinated before the end of 2020.  But everyone else will have to wait for manufacturing to ramp up.  Unfortunately this vaccine must be maintained frozen at -100 degrees F, and there must be national plan for distribution to accomplish that.

Posted by Shirley at 7:12 AM | Permalink | Comments (1)