Pharma Protects Patients Against Government: A COVID VACCINE Paradigm Shift

As a public service, paindr.com will continue to post content that focuses on practical and political matters related to COVID-19.  Here today are PharmD Candidates Evan Horan and Abigail Healey under the mentorship of Dr. Jacqueline Cleary and yours truly.  Here’s what they had to say…

The novel COVID-19 pandemic took the world by storm in the early months of 2020. To date there have been 53,021,603 confirmed cases with 1,297,347 deaths worldwide. The US currently leads all countries with cumulative cases 10,582,938 and, unfortunately, total deaths with 242,710. Coronavirus is easily transmitted via respiratory particles that can be passed along from talking, coughing, or sneezing. Since sequencing the viral genome, development of a vaccine has become a top priority. Operation Warp Speed is a public-private partnership aimed at providing the world with a safe and effective COVID-19 vaccine by January 2021. Although it is good news to hear a global alliance dedicated to vaccine development, there are several concerns.

The proposed timeline is unrealistic compared to the vast history of vaccine development. From the design phase through clinical trials involving thousands of participants, vaccine development usually takes a decade or two. The proposed release date of January 2021 is just shy of 1 year from the first detected case in the US, and just 9 months after the World Health Organization declared COVID-19 a global pandemic. The safety data alone takes years to prove there are no long-lasting adverse events and even more time to prove the vaccine has durable efficacy. There are currently several vaccines in large-scale Phase 3 clinical trials and some that are approved for limited use. The FDA recently released a guidance for industry relating to Early Use Authorization. In this release, they mention that a COVID-19 vaccine would have to protect at least 50% of vaccinated people to be considered efficacious. It appears that the government is pushing for a vaccine to be publicly available as soon as possible, however, a majority of companies involved with vaccine development recently issued a statement that they will stand with science and not put forward a vaccine that has not been thoroughly tested for safety and efficacy.

Back in September, incumbent President Donald Trump, claimed the U.S. government could start distributing a coronavirus vaccine as early as October, completely contradicting the CDCs timeline. He claimed the US has already gathered and prepared the necessary supplies and is ready to distribute at least 100 million doses starting in October or November. Dr. Robert Redfield, Director of the CDC, expects vaccinations to begin in late November and December, although in significantly limited quantities. His estimate is that it will take an additional six to nine months before the entire American public is vaccinated and allowed to resume normal life. And as you can imagine, President Trump rebutted this information claiming the Director of the CDC was confused and misunderstood, again emphasizing “We’re ready to go immediately as the vaccine is announced and it could be announced in October, it could be announced a little bit after October but once we go we’re ready.”. Since the election President Trump has made little to no comments on the status of the COVID vaccine, while President-elect Biden has formed a task force without a release of transition funding. He has made it evident that public health and managing the pandemic as it escalates are his top priorities.

Vaccine Candidates

Multiple drug companies have vaccine candidates in Phase 3 clinical trials including: Moderna, AstraZeneca, Johnson & Johnson, and Pfizer/BioNTech. Moderna’s vaccine (mRNA-1273), encodes the receptor binding domain of the SARS-CoV-2 spike protein. Formulated in lipid nanoparticles, the candidate appears to be a safe and well tolerated vaccine with only one grade 3 erythema event reported and other notable events reported with the 250 microgram dose. The US recently began trials in August enrolling adults aged 18 or older in which 20,000 participants will receive the vaccine and 10,000 will be randomized to the control group.

AstraZeneca developed a chimpanzee adenovirus-vectored investigational vaccine (ChAdOx1/AZD1222) encoding the spike glycoprotein of SARS-CoV-2. The candidate showed strong promise when the study showed induction of humoral immune response after the first dose, and additional increase after the second dose. Common adverse effects such as pain and tenderness at the injection site, malaise, muscle aches, chills, and nausea were generally mild and likely to occur within 4 to 5 days. Interestingly enough, the trials protocol was amended to include paracetamol for use as a prophylactic agent reducing local and systemic reactions to the vaccine. The early phase trials were temporarily halted due to a participant developing neurologic symptoms, which was later linked to multiple sclerosis. During the phase 3 trial, a woman in the UK experienced neurological symptoms consistent with a rare but serious spinal inflammatory disorder called transverse myelitis. The company issued a statement expressing the “standard review process triggered a pause to vaccination to allow review of safety data”. On September 9th, the director of the National Institutes of Health, Francis Collins, commented “To have a clinical hold, as has been placed on AstraZeneca as of yesterday , because of a single serious adverse event is not at all unprecedented,”. He followed that statement with, “This certainly happens in any large-scale trial where you have tens of thousands of people invested in taking part, some of them may get ill and you always have to try to figure out: Is that because of the vaccine, or were they going to get that illness anyway?”. The trial remains on hold in the US leaving many vaccine researchers in the dark.

Johnson & Johnson, another large pharmaceutical manufacturer of the COVID-19 vaccine halted their trial temporarily after a trial participant had an unknown illness. In Johnson & Johnson’s statement they explain to the public the difference between a study pause and regulatory hold of a clinical trial. This stresses the point that their trial is on pause at the moment and that this was initiated by the company to protect their participants, and that this was not a regulatory hold set in place by the Food & Drug Administration (FDA). Their vaccine, JNJ-78436735, was progressing in Phase 3 ENSEMBLE trial prior to being placed on a pause.

In recent news, the vaccine candidate BNT162b2, manufactured by Pfizer, claims to have a 90% efficacy rate. Last week, Pfizer’s chief executive officer said the company would not apply for emergency use authorization for its vaccine until at least the third week of November, when it plans to have sufficient safety data.

A major concern with the rapid production of vaccines can be related to other events in history. The Cutter Incident, in April of 1955, resulted from the vaccination of more than 200,000 children with a polio vaccine in which the process of inactivating the virus was defective. As a result, there was a reported 40,000 cases of polio with 200 children having various degrees of paralysis and killing 10. In 1976, patients that were immunized with the swine flu vaccine resulted in an increased risk of developing a serious neurological disorder called Guillain-Barré Syndrome (GBS) that may also cause a chronic pain syndrome. When over 40 million people were vaccinated against swine flu, federal health officials decided that the possibility of an association of GBS with the vaccine, however small, necessitated stopping immunization until the issue could be explored. 27 years later, The Institute of Medicine (IOM) conducted a scientific review of this issue and concluded that people who received the 1976 swine influenza vaccine were at an increased risk for developing GBS. In recent years other vaccines have shown evidence of a causal relationship between vaccines and adverse events. The MMR vaccine has been shown to cause transient arthralgia (joint pain) in female adults and children. The live varicella zoster vaccine has been associated with widespread chickenpox rash, vaccine strain viral reactivation (appearance of chickenpox months to years after vaccination), and reactivation with subsequent infection resulting in either meningitis The inactivated influenza vaccine as well as the rabies vaccine has been noted to cause nervous system disorders such as GBS. Although the incidence of these long term adverse effects is rare, they still have the potential to occur and have only been noted due to long term monitoring after the patient has been immunized. That’s the issue with producing a vaccine in 9 months (as it appears the COVID-19 will be), there is no long-term data to definitively rule out the occurrence of adverse events down the road. The government is pressuring drug companies to submit data from trials to speed vaccine approval there is thought to be a large financial payout for the economy when this vaccine hits the market.

It is both alarming and reassuring to hear of the reported adverse event with AstraZeneca and Johnson & Johnsons candidates. On one hand you have a serious adverse event that’s possibly related to the trial vaccine. On the other hand, it’s reassuring that the manufacturers are placing patient safety at the forefront. To be the first trials placed on hold due to an adverse event is a big statement to the world. It shows the companies are dedicated to making a vaccine that is not only effective, but safe to everyone receiving it. AstraZeneca has paused and allowed time for scientists to examine the vaccine and the patient with the event to associate a correlation between the two. In the meantime, they’ve already protected the rest of their trial participants by halting the study. This news has been passed to other vaccine developers to watch out for similar neurologic adverse events to (potentially) identify a link with the vector. Despite the pre-election pressure (from POTUS) to get an effective vaccine out to the public prior to the November Presidential election, drug companies have sided with the patient. They have stated that patient safety is their main focus and will not be subject to pressure or political agendas no matter the financial consequences. These companies are being overly cautious with rolling out their vaccines as they do not want to put patients at risk with a vaccine that may not be suitable for the public.

 Assuming that we do soon see a vaccine, the rate limiting bottleneck for getting it to patients may very well be logistics around deep freeze temperatures required for these products, including but not limited to shipping and storage at the distributer site.  And for certain, physician offices, community pharmacies, and most hospitals do not have such freezers on site.

With all the attention to purported Big Pharma greed, let’s not forget that the Pharma industry paid for research and resources towards a safe and effective COVID-19 vaccine.

It seems quite ironic that instead of the US Government protecting patients against a dangerous product, that the Pharm Industry is has taken a lead role to protect patients against the government – go figure! With that in mind, we remain excited about COVID-19 vaccine release and eventual protection against this deadly disease with a product shown to be both safe and effective by regulatory standards.

As always comments and questions are welcome!

 

Evan Horan is currently completing his last year of APPE rotations and will expect to graduate from Albany College of Pharmacy and Health Sciences in May 2021. After school, he plans to complete a PGY1 Pharmacy Practice Residency and PGY2 Residency in Ambulatory Care with the hopes of becoming a board certified pharmacist. Evan’s interests lie in cardiology, pain management, endocrinology, and primary care. Outside of school, Evan is very active outdoors enjoying activities such as golfing, hiking, boating, camping, and skiing.

 

 

 

Abigail Healey is completing her APPE rotations and is expected to graduate from Albany College of Pharmacy and Health Sciences in May of 2021 with her Doctor of Pharmacy. She currently works at Saratoga Hospital in the emergency department as well as at Price Chopper as a Pharmacy Intern. Abigail has varied interests in community pharmacy, critical care, and emergency medicine with hopes to possibly pursue both paths. Abigail enjoys spending time with family, being outdoors, and playing with her dog Moose.

 

 

 

Dr. Cleary obtained a bachelor’s degree from Furman University and her Doctor of Pharmacy from the Medical University of South Carolina.  She completed both PGY1 and PGY2 pharmacy practice residencies and is currently an Assistant Professor at the Albany College of Pharmacy and Health Sciences in the Department of Pharmacy Practice.  Her current practice site is Saratoga Hospital Medical Group Community Health Center in Saratoga Springs, NY where she serves as clinical pharmacist specialist.  Dr. Cleary loves to garden, cook and chase after her two boys.