Last month, I reported on 4 U.S. phase 3 vaccines in development which was spurred due to the release of clinical trial protocols to the public. Although no new protocols have been released, events have occurred since then that may impact the trajectory of the vaccines that launch into the market, which are discussed below.
This month’s chart adds two more phase 3 candidates. One is Novavax’s Nvx-Cov2373 vaccine. What makes this unique is that it is being tested in conjunction with a flu shot. If successful, the company has expressed interest to one day combine the dual technology of COVID/Flu together as an administration. Also added to and being deleted from the chart is a treatment: Eli Lilly’s bamlanivimab in combination with remdesivir or another standard of care (SOC). This is not intended to prevent COVID-19, so it is not a vaccine. It is an intravenous (IV) medication being studied in hospitalized patients who have been diagnosed and are suffering from COVID-19. This treatment filed for EUA but has since terminated the trial in severe hospitalized patients due to lack of efficacy benefit. They plan to continue trials in patients with earlier disease.
Below are observations from the abbreviated chart above. A full chart can be found here.
OBSERVATIONS:
• None of the U.S. vaccines are being studied in children under the age of 12. Pfizer recently lowered the enrolment age from 16. This leaves daycare, preschool, and elementary school children unprotected. And if the Pfizer compound BNT162 does not launch, coverage will begin at age 18 and older in the U.S. This would leave all school age children vulnerable.
-As mentioned in the previous blog, there is a UK arm of the Astra Zeneca trial enrolling children ages 5-12. IF AZD1222 launches this would provide data that US physicians could reference and possibly lead to an option for off-label prescribing in the U.S.
It is important to note that at launch there will be no data in patients with respiratory diseases and data for healthy people over the age of 65 will most likely be limited. Even if you are eligible to receive the vaccine, this will not have pronounced effects on your daily life if you interface with a friend, relative, classmate, or stranger who is a child, senior, or anyone with respiratory conditions. Currently, it is unknown if a vaccinated person can still carry and spread the virus, and for how long one may be immune.
• Emergency Use Authorization (EUA) will allow for broad utilization of a drug up to 2 years prior to trial completion, but what happens if an EUA candidate does not receive a formal FDA indication?
A typical phase 3 trial has a 50% chance of moving to the approval phase. In the cases where technologies have been previously proven, the risk decreases. Based on those odds, one could deduce that out of 5 or 6 U.S. phase 3 trials, 3 or 4 may be approved.
Moderna and Pfizer have stated they are on track to file for EUA in 2020. Others may follow soon thereafter.
Should an EUA candidate NOT receive a formal FDA indication, that drug would be pulled from market (lose its EUA status) and those that were vaccinated would likely need to be re-vaccinated.
The obvious concern for anyone considering getting vaccinated is “what does that mean for my health?” That is the unknown risk. However, to curtail safety complications, the FDA published an EUA Guidance for Industry regarding Vaccines to Prevent COVID-19 earlier in October.
This document states that the benefits of an approved vaccine must outweigh the risks and goes on to outline minimal safety (and efficacy) hurdles believed to meet such a requirement:
The efficacy hurdle is to prove decreasing disease severity in at least 50% of people who are vaccinated.
For safety, it is not as simple. Here are highlights of the outlined criteria. Manufacturers must include a follow-up, with a median duration of at least two months post-completion of the full vaccination regimen. Two months allows enough time for memory immune responses to the vaccine to create a protective effect, as opposed to innate responses which occur sooner. Trials must include over 3,000 vaccine recipients who are followed for serious adverse events and adverse events of special interest. They must also ensure there are measures in place to show the vaccine is at low risk for inducing Enhanced Respiratory Disease (ERD) which is when a vaccine can trigger enhanced side effects.
The guidance clearly states that an EUA issuance will not interfere with the ability of an ongoing phase 3 trial to demonstrate effectiveness and to continue safety assessments that will support a Biologic License Application (BLA) submission and FDA approval. Overall, the FDA is putting many safety checks into play, which is great news.
Based on the chart, I would estimate that a vaccine with ‘traditional’ market approval may arrive in 1Q 2023. Given EUA, a vaccine may be available to the public as early as 1Q 2021. Whether to get vaccinated with the EUA vaccine available within the next few months or waiting longer to get vaccinated once trials are completed is a personal choice.
Is getting vaccinated enough to protect yourself and loved ones from contracting COVID-19? The answer is no. An important takeaway to protect those you care about and help the frontline health workers is to social distance, wear a mask, get tested, participate in contact tracing and quarantine exercises, and wash your hands. Basic stuff. You can do it.
Please post questions, comment, share your vaccine observations, and suggestions for future blogs!
___
Deb Alper from Alper Consulting LLC, is a strategic marketing consultant who partners with early development oncology divisions, rare disease companies, and agencies to provide commercial guidance to strategic planning, new product launch preparation, early to late phase programs, life cycle planning and portfolio prioritization.
___
ABBREVIATIONS and DEFINITIONS
AE: Adverse Event
BARDA: Biomedical Advanced Research & Dev. Authority, part of the Office of Assistant Secretary for Preparedness and Response at the US Dept of Health and Human Services (HHS)
EUA: Emergency Use Authorization
NIAID: National Institute of Allergy and Infectious Disease
NIH: National Institute of Health
Estimated Completion Date: is the date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (the last participant’s last visit).
Regulatory Approval process: occurs after the Estimated Completion Date.
SOURCES
S1 https://s3.amazonaws.com/ctr-med-7111/D8110C00001/52bec400-80f6-4c1b-8791-0483923d0867/c8070a4e-6a9d-46f9-8c32-cece903592b9/D8110C00001_CSP-v2.pdf
S2 https://clinicaltrials.gov/ct2/show/NCT04516746
S3 https://www.beckershospitalreview.com/pharmacy/astrazeneca-releases-covid-19-vaccine-protocol.html
S4 https://www.modernatx.com/sites/default/files/mRNA-1273-P301-Protocol.pdf
S5 https://clinicaltrials.gov/ct2/show/NCT04470427
S6 https://pfe-pfizercom-d8-prod.s3.amazonaws.com/2020-09/C4591001_Clinical_Protocol_0.pdf
S7 https://www.cnn.com/2020/09/08/health/pfizer-biontech-vaccine-october-intl-grm/index.html
S8 https://clinicaltrials.gov/ct2/show/NCT04368728?term=BNT162&phase=2&draw=2&rank=1
S9 https://clinicaltrials.gov/ct2/show/NCT04505722?term=Ensemble&cond=Covid19&phase=2&draw=2&rank=1
S10 https://www.jnj.com/johnson-johnson-initiates-pivotal-global-phase-3-clinical-trial-of-janssens-covid-19-vaccine-candidate
S11 https://www.jnj.com/coronavirus/covid-19-phase-3-study-clinical-protocol
S12 https://www.pfizer.com/science/coronavirus/vaccine
S13 https://clinicaltrials.gov/ct2/show/NCT04501978?term=LY3819253&draw=2&rank=6
S14 https://www.nytimes.com/2020/09/24/health/covid-19-vaccine-novavax.html
S15 https://www.bizjournals.com/washington/inno/stories/news/2020/10/27/here-s-the-latest-on-novavax-s-covid-19-vaccine-tr.html
S16 https://www.nytimes.com/live/2020/10/26/world/covid-19-coronavirus-updates
