The Race To A New Normal: A COVID-19 Vaccine Pipeline Update
The medical community has been feverishly working toward a COVID-19 vaccine and we are now confident one is on the horizon. As of October 10, the pipeline which began with 200 potential vaccines has recently narrowed to seven in phase 3 clinical trials indicating we can expect a successful product to market.
While vaccine manufacturers have yet to publish initial results, political pressures and the CDC have suggested that there may be limited supplies of vaccine available by the end of 2020. The CDC is developing recommendations for vaccine distribution and access based on input from the Advisory Committee on Immunization Practices (ACIP).
There are three types of vaccines under development: RNA vaccines, traditional inactivated vaccines and adenovirus vector vaccines.
Inactivated virus vaccines are also in development by China based companies, Sinovac and Sinopharm. These types of vaccines have a long history for being effective however, the ability to scale production and storage of these products poses difficulties. Inactivated vaccines are made from inactivated (or dead) virus. Injection of the inactivated virus mimic the viral infection and stimulates the body’s immune response to produce antibodies.
T Sinovac’s vaccine is currently in phase 3 trials, but information is limited regarding recruitment. Sinovac seems to be focused on high-risk populations for their trials, which has not been as much of a focus in other trials.
The information is extremely limited regarding the two Chinese developed products, but the Chinese military has approved the Sinopharm vaccine for use. This was reportedly tested among 50,000 participants. Based on the limited data available, it is unlikely this product will be first to market in the US.
Pfizer and Moderna are currently in phase 3 trials for an RNA vaccine that contains messenger RNA (mRNA) that the body then translates to create proteins similar to that of the virus, called antigens. The body’s immune system recognizes the antigens and then creates the antibodies needed to fight off the virus.
Per the Harvard Medical School, while RNA vaccines provide an opportunity to bring a product to market on a large scale with relatively low cost, the primary drawback is that they are still novel and there are many unknowns.
As both Moderna and Pfizer embark on phase 3 clinical trials, initial efficacy data is expected as early as November, but safety data will take longer.
Adenovirus Vector Vaccines
Adenovirus Vector vaccines leverage an existing virus that is altered to produce the SARS-CoV-2 protein. This process is intended to elicit an immune response to the virus. While the nature of this vaccine is anticipated to develop a more robust immune system response in patients, the drawback is that the immune response may not be effective among patients with existing robust immune systems, particularly those with prior adenovirus exposure. The necessary protein would theoretically be unable to create an antibody response because the bodies existing antibodies would break it down prematurely.
The three vaccines in phase 3 clinical trials come from AstraZeneca, CanSinoBio (China) and Gamaleya (Russia). AstraZeneca’s vaccine tackles the primary concern of existing immunity by using a chimpanzee adenovirus as the vector for their product. While patient enrollment has been strong, the trial was recently paused and then restarted after a patient developed transverse myelitis. Transverse myelitis is an inflammation of both sides of one section of the spinal cord.
CanSinoBio’s vaccine uses adenovirus 5 vector, which does not address the concern of existing immunity. Many people already have immunity to this particular adenovirus rendering this product less effective for those patients.
Russian based Gamaleya has elected to combine adenovirus 5 and 26 as their vectors. This vaccine’s viability is unlikely across multiple markets due to a lack of confidence in the data quality.
Emergency Use Authorization
Most analysts agree that the FDA will consider an emergency use authorization (EUA) for one or more of these agents. It will be crucial to understand if the Vaccines and Related Biological Products Advisory Committee, a group staffed by completely independent scientists, has vetted the data along with details surrounding the vote for approval.
Confidio clinicians are concerned that the trials are not representative of Americans; study participants are primarily a Caucasian population. Underrepresented minorities are not well represented, nor are the aged or children. Will the committee approve if there is no clear safety and efficacy data in these groups?
Bottom line, an EUA without the endorsement of the Vaccines and Related Biological Products Advisory Committee is a red flag. An EUA with its approval may be the best way to get people vaccinated quickly. Where will the vaccines be administered?
Vaccines are administered in physicians’ offices under the medical benefit, but many are also administered by pharmacists at pharmacies and covered under the pharmacy benefit. The Department of Health and Human Services has authorized state-licensed pharmacists to order and administer COVID-19 vaccinations once available to patients. COVID-19 vaccines are likely to be handled similarly to the Influenza (Flu) vaccines once they become available.
Due to the sizable number of Americans who will seek vaccinations, a “herculean” effort will be employed to reach as many people as possible by providing access to as many authorized healthcare providers and professionals as possible.
While many remain hopeful for a vaccine to come to market as prior to the end of this year, it is unlikely we will see the necessary approval and production at scale before 2021.
We are faced with a two-fold challenge to develop a safe, effective product that can quickly be produced and distributed on a massive scale. It will be imperative to provide transparency allowing patients and practitioners to make an informed decision based on unbiased analysis.
A vaccine is undoubtedly on the horizon, but with many unknowns regarding the pipeline products, we cannot confidently put a realistic timeline around wide-spread availability. The medical community is working tirelessly to collaborate and develop a product that will hopefully get us back to a normal, or at minimum, a new normal, as quickly as possible. In the meantime, we can all take action to continue to wear masks in public, practice social distancing and proper hand hygiene.
- PHG Foundation. RNA vaccines: an introduction. University of Cambridge. Retreived 22 Sep 2020 from https://www.phgfoundation.org/briefing/rna-vaccines
- Wilson, F.Perry. The COVID Vaccine Derby: A Guide to the Top Contenders. Retrieved 24 Sep 2020 from https://www.medscape.com/viewarticle/937337
- Hubaud, Alexis. RNA Vaccines: A Novel Technology to Prevent and Treat Disease. Retrieved 22 Sep 2020 from http://sitn.hms.harvard.edu/flash/2015/rna-vaccines-a-novel-technology-to-prevent-and-treat-disease/
- State of COVID Vaccine Development (October 2002). Retrieved from https://www.optum.com/business/resources/library/covid-19-vaccines-update.html?utm_campaign=RX_8.1_2020&utm_medium=EM&utm_source=EM&utm_term=2020kvt2z10dh5&elq_mid=24132&elq_cid=4319761