Five Companies Edging Closer to SARS-CoV-2 Vaccine Emergency Use Authorization
Global COVID-19 cases have been spiking in Europe and the U.S. as the predicted second wave is hitting communities hard, applying new pressure on hospital capacity and forcing local and state governments to once again tighten restrictions.
Pfizer’s recent announcement that its SARS-CoV-2 vaccine candidate was 90% effective was welcome news to people around the globe. Pfizer’s positive interim data is encouraging, but more work is required to validate the vaccine candidate’s efficacy and safety before it can receive Emergency Use Authorization (EUA) from the Food and Drug Administration for distribution in the United States.
Top infectious disease expert Dr. Anthony Fauci anticipates the Pfizer vaccine being available to higher risk groups by the end of 2020 with lower risk groups potentially receiving the vaccine by April 2021. Pfizer’s vaccine is promising, for sure, but the more vaccines that are proven effective and safe, the better.
Various vaccine modalities and approaches are being explored to combat SARS-CoV-2. Life science companies across the globe, including many within the BioHealth Capital Region (BHCR), are deeply engaged in the pandemic fight. According to the New York Times COVID-19 vaccine tracker, 38 SARS-VoV-2 vaccines are in Phase I; 14 are in Phase II; 11 are in Phase II; and 6 vaccines have been approved for early/limited use, including several in China and Russia.
Not all of them will make it to the finish line, but Pfizer and several other companies are getting closer to approval and initial distribution.
We thought it a good time to take a look at the top five SARS-CoV-2 vaccine candidates being developed by European and U.S. life science companies that are closest to EUA approval in the United States.
Pfizer, Inc. and BioN-Tech SE
BNT162b2 Vaccine Candidate
Pharmaceutical giant Pfizer, Inc, and the Germany-based immunotherapy company BioN-Tech SE, have partnered to advance their MRNA-based SARS-CoV-2 vaccine candidate BNT162b2. The companies recently announced interim analysis of the vaccine’s Phase III study results. The Phase III study commenced in late July 2020 and has a recent enrollment count of 43,538, 38,955 of which have received a second vaccine dose.
BNT162b2 is an MRNA, or messenger RNA, based vaccine, like Moderna’s vaccine candidate. An MRNA-based vaccine has never been approved for use. MRNA-based vaccines are different from traditional influenza vaccines, for example, which inject subjects with dead virus or attenuated, or weakened, live viruses to generate an immune response.
MRNA-vaccines, on the other hand, deliver genetic instructions for cells to make antigens (spike proteins) themselves, which turns the body into a vaccine machine as it generates antibodies to fight these antigens. This is all created without ever exposing a patient to the actual virus. MRNA-based vaccines can be developed and fine-tuned more quickly than more traditional vaccines; however, one disadvantage is that the vaccine requires very cold temperatures for storage.
BNT162b2 is a two-dose vaccine and the interim analysis showed “…The case split between vaccinated individuals and those who received the placebo indicates a vaccine efficacy rate above 90%, at 7 days after the second dose.” The study reported no safety concerns. The vaccine candidate will continue to be evaluated for efficacy and safety, but Pfizer and BioN-Tech anticipate filing for EUA from the FDA in the next few weeks. The companies anticipate producing 50M vaccine doses in 2020 at locations across the globe and to increase production to 1.3B doses in 2021.
Protein-based Vaccine Candidate NVX-CoV2373
Gaithersburg, Maryland’s Novavax recently announced that its SARS-CoV-2 vaccine candidate NVX-CoV2373 had received Fast Track Designation from the FDA, marking the latest milestone as the company advances its protein-based product towards EUA and commercialization.
This announcement comes on the heels of Novavax announcing a clinical trial delay in the U.S. and Mexico caused by challenges scaling up vaccine manufacturing. This is the largest of the Novavax trials from an enrollment standpoint and it is expected to begin toward the end of November 2020.
In August the company launched a Phase II trial in South Africa with 2,900 participants. This trial is ongoing. The company’s Phase III trial in the U.K. has continued moving forward as well; the U.K.-located trial has enrolled approximately 5,500 participants and is expected to expand this number to about 15,000. The U.K. trial is expected to produce data at some point in Q1 2021.
Novavax has received $1.6B in funding from Operation Warp Speed to advance its vaccine candidate. In addition, the company has received over $400M in combined funding from the U.S. Department of Defense ($70M) and the Coalition for Epidemic Preparedness ($384M).
Unlike Pfizer and Moderna’s vaccine candidate, Novavax’s NVXCoV2373 is a stable, prefusion protein made using the company’s nanoparticle technology and its proprietary MatrixM™ adjuvant. According to Novavax, the vaccine candidate uses “…our recombinant nanoparticle technology to generate antigen derived from the coronavirus spike protein. In combination with our proprietary Matrix-M™ adjuvant, NVX-CoV2373 has demonstrated in preclinical studies that it binds efficiently with human receptors targeted by the virus, a critical aspect for effective vaccine protection.”
Two recent manufacturing deals have positioned Novavx well from a vaccine distribution standpoint should their candidate receive approval. Novavax projects that it will be able to deliver approximately $100M vaccines doses by the first quarter of 2021.
Moderna and the National Institute of Allergies and Infectious Diseases (NIAID)/National Institutes of Health (NIH)
mRNA-1273 Vaccine Candidate
Moderna, in conjunction with the NIAID/NIH and government funding support from Operation Warp Speed, has advanced its MRNA-based vaccine candidate to Phase III clinical trials. Moderna’s and Pfizer/BioN-Tech SE’s trial began in the same late July 2020 time frame. Moderna has enrolled 30,000 participants in the Phase III trial, which, like Pfizer’s vaccine candidate, is a two-dose regimen. Of the 30,000 enrolled in the trial, 25,564 have received their second vaccine dose.
Moderna anticipates reporting its interim results toward the end of November 2020 and could apply for vaccine EUA by the end of the year, or even as early as December 2020.
Pfizer/BioN-Tech SE’s positive interim results present a mixed bag for Moderna; on one hand, Pfizer is ahead in the approval process, but on the other, the similar vaccine mechanisms of action shared by the two companies bodes well for Modern’s interim results.
Johnson & Johnson/Janssen Pharmaceutical Companies, Beth Israel Lahey Health
Viral Vector-based Vaccine Candidate, JNJ-78436735
In March 2020, Johnson & Johnson (J&J) received $456M in Operation Warp Speed funding for its viral vector-based SARS-CoV-2 vaccine candidate. J&J’s candidate is unique among late-stage vaccine candidates in that it requires a single dose.
J&J’s ENSEMBLE 60,000 participant SARS-CoV-2 Phase III trial was recently paused due to an adverse event. On October 23rd, 2020, however, J&J announced they had received the go ahead to resume the pivotal Phase III trial.
Put simply, viral vector vaccines – in J&J’s case using Adenovirus 26 (AD26)- deliver live but chemically weakened virus into the body to create an immune response. Viral vector vaccines carry DNA into a host cell to produce antigen proteins that can be customized to trigger specific immune responses.
J&J’s vaccine candidate is based on AD26 and is being developed in collaboration with Beth Israel Deaconess Medical Center, which is part of the Beth Israel Lahey Health System, Beth Israel has a long history using AD26 to develop vaccine platforms. According to a recent J&J press release, “The Janssen COVID-19 vaccine candidate leverages the Company’s AdVac® technology platform, which was also used to develop and manufacture Janssen’s European Commission approved Ebola vaccine and construct its Zika, RSV, and HIV vaccine candidates. Janssen’s AdVac® technology platform has been used to vaccinate more than 100,000 people to date across Janssen’s investigational vaccine programs.”
J&J anticipates EUA in the first quarter of 2021 should its Phase III trial prove its vaccine candidate to be safe and effective.
AstraZeneca (AZ), University of Oxford/Vaccitech
Viral Vector Vaccine Candidate, AZD1222
Phase II/III Combined
For some time, AstraZeneca, in collaboration with the University of Oxford, was the leading vaccine candidate and appeared to be closest to EUA. As part of Operation Warp Speed, AZ secured a $413.2M Department of Health and Human Services (DHHS)/BARDA contract. DHHS has also pledged up to $1.2B in funding support for AZ for 300M doses of its vaccine candidate AZD1222. The vaccine technology was developed by the University of Oxford and its spin-out company Vaccitech and licensed to AZ.
Like many of the other leading vaccine candidates, AZ’s vaccine has a two dose regimen. According to an AZ press release, AD1222 “…uses a replication-deficient chimpanzee viral vector based on a weakened version of a common cold virus (adenovirus) that causes infections in chimpanzees and contains the genetic material of the SARS-CoV-2 virus spike protein. After vaccination, the surface spike protein is produced, priming the immune system to attack the SARS-CoV-2 virus if it later infects the body.”
AZD1222’s Phase 3 clinical trial in the U.S. includes up to 30,000 patients, and there are also trials ongoing in India, England, South Africa, and Brazil that includes approximately 23,000 patients. All Phase III trials were halted on September 6, 2020, due to an adverse event that occurred during the U.K. clinical trial. After a pause, the regulatory agencies where trials are occurring approved all Phase III trials to restart. The FDA was the last regulatory agency to approve the restart.
Interestingly, initial trial data for AD1222 showed positive outcomes for patients over 56 and even over 70 years of age, which makes AZ’s product unique – for the time being – among the leading vaccine candidates.
Despite the pause in the U.S. Phase III trial, AZ hopes to report its late stage trial data before the year’s end, which could position the vaccine candidate well for EUA in the first part of 2021.
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