COVID-19 is a household term in 2020. It has impacted every aspect of daily life. As of September 8, 2020, there are 27.1 million confirmed cases of coronavirus accounting for over 889,981 deaths worldwide, with the United States accounting for 188,603 deaths and 6.2 million cases. While the number of new cases are declining across the U.S., numbers continue to rise around the world, leaving people desperate for a solution.
Perspective on the Rx Pipeline: COVID-19 Vaccine
Current efforts have been guided toward prevention through enhanced precautions of self-quarantine, mask requirements and social distancing. Additionally, international and national research is being conducted to develop a safe and effective vaccination to create immunity from contracting the virus. Vaccine immunization would allow the immune system to be exposed to an inactivated form of the virus, which would create antibodies to protect against infection.
Traditional Vaccine Development Process: The usual course for vaccine development is lengthy and rigorous.[3-5]
- Research - Two to four years detailed laboratory research on the proposed immunization.
- Pre-Clinical Period - Promising vaccine candidates move on to a pre-clinical period, lasting between one to two years, where laboratory animals are used to establish safety and efficacy.
- Phase 1 Clinical Trials - A small group of healthy participants are chosen to take part in the first clinical phase to determine the safety profile, appropriate dose and ability to produce an immune response in humans.
- Phase 2 Clinical Trials - Eligible vaccines move into second phase trials where they are then compared against a placebo to further assess the safety and efficacy of the vaccine in a wider population of hundreds of participants over two to three years.
- Phase 3 Clinical Trials - The final phase of clinical trials, prior to approval, includes thousands of participants randomized to receive the vaccine or a placebo in a blinded fashion and can take up to five years. Again, the purpose is to establish safety and effectiveness, but with a larger population, a more robust side effect profile can be identified.
- Biologics License Application (BLA) - After the conclusion of clinical trials, a BLA is submitted to the Food and Drug Administration (FDA) and, upon approval, the vaccine can be manufactured on a mass scale.
- Research - At the start of the pandemic, researchers began trying to decipher the SARS-COV-2 genome (the genome that produces COVID-19) in order to develop a vaccine. Researchers were also able to use data that was previously collected from the SARS outbreak in the early 2000s to apply to developing a COVID-19 vaccine.
- Pre-Clinical Period - Limited research time is followed by shortened pre-clinical trials.
- Combined Multi-Phase Clinical Trials - Clinical trial phases are often combined to further speed up the process.[6,7] For example, phase 1/2 trials can measure safety, efficacy and appropriate dose in hundreds of patients over just a few months. Another consideration is the number of people that are available to participate in clinical trials during this global pandemic.
- Manufacturing - Additionally, mass manufacturing starts early, prior to formal approval. This introduces a significant financial risk to the companies developing the vaccines, as well as their investors. Because of the financial uncertainties involved with manufacturing a large amount of a vaccine that is not yet approved, a recent government program known as Operation Warp Speed (OWS) has been developed. OWS provides funding to vaccine developers to encourage rapid manufacturing of a safe and effective COVID-19 vaccine. The goal of OWS is to deliver 300 million doses of safe, effective vaccines for COVID-19 by January 2021. Some researchers believe it is optimistic to think that Americans will have access to vaccines as early as January 2021.
Safety Concerns: With such a short development timeline, concerns have been raised for the safety of potential vaccines. It is important to know that the FDA still requires vaccines to meet quality standards in the midst of a pandemic. A vaccine will not be approved until complete safety and efficacy data are available. Based on the FDA’s guidance, vaccines would have to have a greater than 50% infection benefit, meaning approved vaccines would need to reduce the risk of COVID-19 by 50%. More data than antibody levels alone is needed to determine the infection benefit since researchers do not know what level of antibodies prevent infection.
As of September 8, 2020, nine drugmakers had their chief executives sign a pledge promising not to file for regulatory approval or authorization of their experiemental COVID-19 vaccines until the vaccinations have shown to work safely through late-stage clinical testing.
Additionally, vaccines, like any drug, have post-marketing follow-up to monitor for potential long-term side effects through the FDA-driven Vaccine Adverse Event Reporting System (VAERS). Through VAERS, anyone with a safety concern following the administration of a vaccine can submit a report for documentation and review.
Summary of Top COVID-19 Vaccine Candidates: As of early September, the World Health Organization (WHO) accounts for 165 COVID-19 vaccines being developed worldwide, with 34 entering human trials. Multiple vaccine mechanisms are in the pipeline to determine if one vaccine mechanism is more successful with infection reduction than others.
Internationally, two vaccines have been approved for use in their respective countries. In China, CoronaVac by Sinovac was given emergency approval for limited use in July. Russia moved Gamaleya Research Institute’s product, Gam-Covid-Vac (Sputnik-V), into phase 3 trials two weeks after the vaccine received a Russian conditional registration certificate, which depends on positive results from the phase 3 trials. Note that these drugs are still being studied for approval and use in the United States.
With a number of manufacturers in the U.S. racing to be the first safe and effective vaccine to market, the FDA is planning an advisory panel meeting on October 22, 2020, to discuss COVID-19 vaccine development. At that time, large-scale clinical trials of the leading candidates from Moderna, Pfizer and AstraZeneca will be well into phase 3 trials. The FDA will make approval decisions separately from the advisory committee, but the advisory committee was formed to support transparency for vaccine development in the U.S.
Phase 3 Vaccine Candidates
*Genetic Vaccines: Vaccines that use one or more of coronavirus’ own gene to provoke immune response. Viral Vector Vaccines: Vaccines that use a virus to deliver coronavirus genes into cells. The cells make viral proteins, provoking an immune response, but the virus cannot replicate.
Note: If studies see adequate results, they can move forward in the approval process before the study is complete.
Please note, prior to publication, on September 23, Johnson & Johnson announced its vaccine candidate, JNJ-7836735, has moved into phase 3 trials. This vaccine will be a one-time injection that can be stored in the refrigerator versus storing at -20 degrees Celsius, as other phase 3 pipeline products.
Vaccine Dissemination: Vaccine campaigns are still being developed to ensure widespread dissemination of a vaccine, once approved, and adequate supply. Draft guidance was released by the National Academies Sciences, Engineering and Medicine recommending a four-phase approach for equitable allocation. The first phase, or “jumpstart” phase, would target frontline health workers, first responders and people at serious risk of infection for vaccination. The panel has also advised that officials should ensure vaccines are available to everyone, no matter their social and economic resources, employment, immigration or insurance status.
Impact to the Pharmacy Care Experience
Pipeline Monitoring and Pharmacy & Therapeutics Review: Elixir’s Pharmacy & Therapeutics (P&T) committee continues to monitor the drug pipeline and FDA approvals. The P&T committee will review the safety and efficacy of a new vaccine once FDA approval is granted. After review, more information will be provided about accessibility and coverage.
In the meantime, we are entering flu season. An additional defense against illness is getting an influenza vaccine. Since the COVID-19 vaccine will most likely not be available to the general public until 2021, there should be no concern of overlap of vaccination for influenza and COVID-19. For more information about flu vaccines and the importance of getting vaccinated, click here.
Payer Action Plan
Continue Social Distancing: Payers and their members should continue to follow current prevention guidance of social distancing, wearing masks and self-quarantine.
Influenza Vaccination: Members should be encouraged to get an influenza vaccination as an additional defense against illness.
 Covid19.who.int. 2020. WHO Coronavirus Disease (COVID-19) Dashboard. [online] Available at: <https://covid19.who.int/> [Accessed 26 August 2020].
 Centers for Disease Control and Prevention. 2020. Coronavirus Disease 2019 (COVID-19) – Prevention & Treatment. [online] Available at: <https://www.cdc.gov/coronavirus/2019-ncov/prevent-getting-sick/prevention.html> [Accessed 26 August 2020].
 Historyofvaccines.org. 2018. Vaccine Development, Testing, And Regulation | History Of Vaccines. [online] Available at: <https://www.historyofvaccines.org/content/articles/vaccine-development-testing-and-regulation> [Accessed 26 August 2020].
 Ifpma.org. 2020. [online] Available at: <https://www.ifpma.org/wp-content/uploads/2019/07/IFPMA-ComplexJourney-2019_FINAL.pdf> [Accessed 26 August 2020].
 Cdc.gov. 2014. Vaccine Testing And Approval Process | CDC. [online] Available at: <https://www.cdc.gov/vaccines/basics/test-approve.html> [Accessed 26 August 2020].
 Lurie, N., Saville, M., Hatchett, R. and Halton, J., 2020. Developing Covid-19 Vaccines at Pandemic Speed. New England Journal of Medicine, 382(21), pp.1969-1973.
 Modernatx.com. 2020. Moderna’s Work On A COVID-19 Vaccine Candidate | Moderna, Inc.. [online] Available at: <https://www.modernatx.com/modernas-work-potential-vaccine-against-covid-19> [Accessed 26 August 2020].
 HHS.gov. 2020. Fact Sheet: Explaining Operation Warp Speed. [online] Available at: <https://www.hhs.gov/coronavirus/explaining-operation-warp-speed/index.html> [Accessed 26 August 2020].
 U.S. Food and Drug Administration. 2020. Development And Licensure Of Vaccines To Prevent COVID-19. [online] Available at: <https://www.fda.gov/regulatory-information/search-fda-guidance-documents/development-and-licensure-vaccines-prevent-covid-19> [Accessed 27 August 2020].
 U.S. Food and Drug Administration. 2020. Vaccine Adverse Events. [online] Available at: <https://www.fda.gov/vaccines-blood-biologics/report-problem-center-biologics-evaluation-research/vaccine-adverse-events#:~:text=The%20Vaccine%20Adverse%20Event%20Reporting,adverse%20events%20associated%20with%20vaccines.> [Accessed 27 August 2020].
 Who.int. 2020. Draft landscape of COVID-19 candidate vaccines. [online] Available at: <https://www.who.int/publications/m/item/draft-landscape-of-covid-19-candidate-vaccines> [Accessed 8 September 2020].
 U.S. Food and Drug Administration. 2020. Coronavirus (COVID-19) Update: FDA Announces Advisory Committee Meeting to Discuss COVID-19 Vaccines. [online] Available at: <https://www.fda.gov/news-events/press-announcements/coronavirus-covid-19-update-fda-announces-advisory-committee-meeting-discuss-covid-19-vaccines> [Accessed 8 September 2020].
 Johnson & Johnson. 2020. Johnson & Johnson Initiates Pivotal Global Phase 3 Clinical Trial of Janssen’s COVID-19 Vaccine Candidate | Content Lab U.S. [online] Available at: <https://www.jnj.com/johnson-johnson-initiates-pivotal-global-phase-3-clinical-trial-of-janssens-covid-19-vaccine-candidate> [Accessed 24 September 2020].
 Nationalacademies.org. 2020. Draft Frameworks for Equitable Allocation of a COVID-19 Vaccine. [online] Available at: <https://www.nationalacademies.org/news/2020/09/national-academies-release-draft-framework-for-equitable-allocation-of-a-covid-19-vaccine-seek-public-comment> [Accessed 8 September 2020].