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Vaccines in Development

Last updated: March 10, 2021  

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The following is a curated review of key information and literature about this topic. It is not comprehensive of all data related to this subject. 

Overview

To date, the FDA has issued an Emergency Use Authorization (EUA) for the Moderna, Pfizer-BioNTech, and Janssen COVID-19 vaccines. Several other COVID-19 vaccine candidates remain in development. For a broad overview, refer to the American Society of Health-System Pharmacists' COVID-19 Vaccine Candidate Tracking Sheet.

Phase 3 Clinical Trial Results

Below is a summary of publicly available information on phase 3 vaccine clinical trials. Some of this information is limited to press releases. We will share such information when higher level data is not available and update once literature has been published. 

Novavax COVID-19 Vaccine (NVX-CoV2373) 

The Novavax COVID-19 vaccine is 2-dose regimen that contains a SARS-CoV-2 prefusion spike protein made by Novavax’s recombinant nanoparticle technology in insect cells, and Matrix M, the company’proprietary adjuvant. Matrix M has also been utilized in Novavax’s influenza vaccine candidatewhich is currently in phase 3 clinical trials, among others. Notably, the candidate does not require freezing; it can bstored in refrigerators at 2-8° C. 

The only publicly-available data regarding this vaccine is limited to press release from Novavax. According to the press release, interim analyses of Novavax’s phase 3 clinical trial in the United Kingdom and phase 2b clinical trials in South Africa show the candidate met its primary efficacy and safety endpoints. In the U.K. trial, the interim analysis included 15,000 clinical trial participants. The press release reports there were 56 cases of COVID-19 in the placebo group and 6 cases in the vaccinated group, yielding a vaccine efficacy of 89.3% (95% CI: 75.2-95.4%). Of the 62 cases, 61 were mild or moderate, and 1 was severe (in placebo group). The vaccine was found to have 85.6% efficacy against the variant strain B.1.1.7 (which was detected in over 50% of the U.K. trial’s RT-PCR-confirmed cases)Serious adverse events were balanced between the vaccine and placebo groups, according to the press release. In a 4,400-volunteer study in South Africa, the vaccine was shown to be 49% effective at preventing mild, moderate and severe COVID-19 disease (29 cases in the placebo group versus 15 in the vaccinated group). When analyzing people in the trial not living with HIV (94% of the study population), efficacy was 60% (95% CI: 19.9 – 80.1). Per the press release, sequencing has been performed on 27 of the 44 cases of COVID-19 that had occurred in the trial at the time of the analysis92.6% of these were due to B.1.351. 

Gam-COVID-Vac (Sputnik V)

Sputnik V is a 2-dose recombinant adenovirus-vectored vaccine that utilizes the adenoviruses Ad26 and Ad5. The vaccine was developed by the Russian Ministry of Health and multiple partners. It is not expected to become available in the United States.

An interim analysis of a randomized double-blind placebo-controlled Phase 3 trial examining the efficacy and safety of Sputnik V among 19,866 participants showed the vaccine met its primary endpoint. The vaccine was administered in a prime-boost regimen consisting of dose 1 (rAd26) and dose 2 (rAd5), 21 days apart. Patients were randomized in a 3:1 ratio, resulting in 14,964 participants receiving two doses of the vaccine and 4,902 receiving placebo. The primary outcome was the proportion of individuals with symptomatic PCR-confirmed COVID-19 on day 21 or more after receiving the first dose (i.e., the day of the second dose and beyond). 16 cases of symptomatic COVID-19 occurred in the vaccinated group (0.1%) and 62 in the placebo group (1.3%), resulting in a vaccine efficacy of 91.6% (95% CI 85.6–95.2). There were no cases of moderate or severe disease in the vaccinated group and 20 cases in the placebo group, resulting in a vaccine efficacy of 100% against moderate or severe COVID-19. 46 serious adverse events occurred in the vaccine group, none of which were thought to be related to the vaccine. There were 7,966 reported adverse events, 94% of which were grade 1.

Oxford-AstraZeneca COVID-19 Vaccine (AZD1222)

In summary:  

  • The Oxford-AstraZeneca COVID-19 vaccine (also known as ChAdOx1 nCoV-19 vaccine and AZD1222) is a non-replicating viral vectored vaccine that utilizes a chimp adenovirus. 
  • The vaccine has not yet been granted emergency use authorization in the United States, but has received emergency authorization in several other countries. In February 2021, the World Health Organization added the vaccine to its Emergency Use List.
  • significant benefit of Oxford-AstraZeneca’s COVID-19 vaccine over the Moderna and Pfizer COVID-19 vaccines is that it can be stored and distributed at 2-8 degrees Celsius (as opposed to the Pfizer-BioNTech and Moderna vaccines, which must be stored frozen, although to different degrees of coldness). 
    • Therefore, it is likely the Oxford-AstraZeneca COVID-19 vaccine will be more accessible to lower-income countries without the type of cold chain needed to distribute the Pfizer-BioNTech and Moderna COVID-19 vaccines. 

Single Dose Administration, And The Influence Of The Timing Of The Booster Dose On Immunogenicity and Efficacy Of ChAdOx1 nCoV-19 (AZD1222) Vaccine (Voysey, February 2021 - preprint, not peer-reviewed). 

Overall, in this interim analysis of several clinical trials, a low-dose-standard dose regimen of ChAdOx1 nCoV-19 had higher vaccine efficacy than standard dose-standard dose. In addition, a single standard dose provided 76% protection against symptomatic COVD-19 in the first 90 days after vaccination. Vaccine efficacy was higher with a dosing interval of 12 weeks or more, compared to 6 weeks or less.

Patient population:

  • The report outlines 2 exploratory analyses from the same study population as reported by Voysey et al in December 2020: the immunogenicity and efficacy of extending the interval between priming and booster doses, and the single-dose vaccine.
  • 17,177 baseline seronegative trial participants were included in the efficacy analysis (8,948 in the UK, 6,753 in Brazil and 1,476 in South Africa). 
  • Individuals were excluded if they had a NAAT+ swab in the first 21 days after the first dose, or had less than 22 days of follow-up.  

Primary endpoint:

  • Symptomatic COVID-19 disease, defined as a NAAT+ swab in addition to at least of the following: fever ≥ 37.8°C; cough; shortness of breath; anosmia or ageusia occurring more than 14 days after the second dose. 
  • An additional secondary analysis was performed of cases occurring more than 21 days after the first dose. 

Key findings: 

  • 332 cases of primary symptomatic COVID-19 occurred more than 14 days after the second dose. 
    • The overall vaccine efficacy across dosing groups was 66.7% (95% CI: 57.4%-74.0%). 
    • 15 hospitalizations occurred in the control group, while none occurred in the vaccinated group.
  • In the group that received 2 standard doses, 74 (0.8%) cases occurred in the vaccinated group and 197 (1.9%) in the control group, resulting in a vaccine efficacy of 63.1% (95% CI: 51.8% - 71.7%). 
  • 61 cases were available for analysis in the low dose-standard dose group; the vaccine efficacy was 80.7% (95% CI; 62.1%, 90.2%).
  • When examining vaccine efficacy in the standard dose–standard dose group after the second dose by time, the vaccine efficacy was 82.4% when the time between doses was 12 or more weeks (95% CI 62.7%-91.7%); it was 54.9% when the time between doses was 6 weeks or less (95% CI: 32.7%-69.7%).
  • In the analysis of the efficacy of a single standard dose of the vaccine, the efficacy against symptomatic COVID-19 in the 90 days following vaccination was 76% (95% CI: 59%- 86%); however, there was not efficacy against asymptomatic infection (vaccine efficacy 16%, 95% CI: 88%- 62%). 

Limitations: 

  • This was an interim analysis of an ongoing clinical trial; longer and more complete follow-up is needed to confirm the results. 
  • The number of patients in the low dose-standard dose group was small.
  • The trials were not designed to determine if vaccine efficacy differed by dose interval.   

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomized controlled trials in Brazil, South Africa, and the UK (Voysey, December 2020). 

Overall, in this pooled interim analysis of 4 clinical trials (ranging from phase 1/2 to 3), ChAdOx1 nCoV-19 was effective and preventing symptomatic COVID-19 disease and was safe at a median time of follow up of 2 months for people receiving 2 doses. 

Study population: 

  • This analysis includes data from blinded phase clinical trials of the vaccine: COV001 (UK), COV002 (UK), COV003 (Brazil), and COV005 (South Africa) 
  • CoV001 and COV005 were phase 1/2 trials, and COV00and COV003 were phase 2/3 and 3, respectively. 
    • The phase 1 study (COV001) included an efficacy cohort and the phase 2 and 3 studies (COV002, COV003, and COV005) expanded enrollment to a wider population of participants with higher likelihood of exposure to the virus, such as health care workers.  
  • Participants were randomized to receive either AZD1222, the meningococcal conjugate vaccine MenACWY(COV001, COV002), MenACWY with the first placebo dose and saline for the second dose (COV003) or saline (COV005).  
  • Participants in the ChAdOx1 nCoV-19 group received two doses containing 5×1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial inadvertently received a half dose as their first dose due to a manufacturing error (low dose) and a standard dose as their second dose (LD/SD cohort).  
  • 23,848 participants were enrolled and 11,636 participants (7,548 in the UK; 4,088 in Brazil) were included in the interim primary efficacy analysis.  
  • >90% of participants were 18-55 years old and white.  
  • Patients were excluded if they had a baseline seropositive status, or if their baseline seropositive status was unknown. 
    • Patients were also excluded if they had NAAT-positive swabs within 14 days after the second vaccination. 

Primary endpoint: 

  • Virologically confirmed, symptomatic COVID-19, defined as a NAAT-positive sample and at least one of the following symptoms: fever > 37.8C, cough, shortness of breath, anosmia or ageusia more than 14 days after a second dose. 
  • Serious adverse events were a secondary endpoint, as were cases occurring more than 21 days after the first standard dose in participants who received only one standard dose.  

Key Findings: 

Efficacy 

  • In pooled analyses of the trials (11,636 patients), there were 131 symptomatic cases of COVID-19 in LD/SD or SD/SD recipients (30 cases in the vaccine arm vs. 101 in the control group).   
    • Vaccine efficacy was 70.4%.   
  • In participants who received two standard-dose vaccines, vaccine efficacy was 62.1% (95% CI 41.0–75.7), whereas in those who received a low dose as their first dose of vaccine, efficacy was higher at 90.0% (67.4–97.0).  
  • From 21 days after the first dose, there were 10 cases hospitalized for COVID-19, all in the control arm.  
  • The analysis met its primary endpoint showing protection from COVID-19 occurring >14 days after receiving 2 doses of the vaccine. 

Safety

  • Safety data was available from 74,341 person-months of follow-up after first dose (median 3.4 months) and 29,060 person-months of follow-up after two doses (median 2 months). 
  • Serious adverse events occurred in 168 participants; 79 of these were in the vaccinated group, and 89 in the placebo group. 
  • Three adverse events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group (transverse myelitis occurring 14 days after the second vaccine dose), one in the control group (hemolytic anemia), and one in a participant who remains masked to group allocation (fever to >40C two days after receiving either the vaccine or placebo).   

Limitations: 

  • Differences in dose amounts and the timing of dose administration between the four trials makes it difficult to consider the populations to be a single cohesive group for analysis. 
  • majority of the participants were white, which may limit generalizability. 
  • The numberof patients older than 55 was relatively small. 
  • Questions remain regarding the optimal dose and timing of dose, but additional trials are underway. 

 

 

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