Category: Moderna

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BioNTech Moderna Pfizer Safety monitoring

Safety Monitoring Updates (March 1, 2021)

At the March 1, 2021 meeting of the Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP), Dr. Tom Shimabukuro, a member of the CDC COVID-19 Vaccine Task Force, provided a safety update on the COVID-19 vaccines from Pfizer-BioNTech and Moderna. This safety update was based on information reported to CDC by both health care providers and people who had received one or two doses of the vaccines as of February 16, 2021. By this date, 55.2 million vaccine doses had been administered in the U.S. Overall, the safety profile of COVID-19 vaccines continues to be reassuring and consistent with safety data observed from the pre-authorization clinical trials. In addition, no unexpected pregnancy or infant outcomes have been observed related to COVID-19 vaccination during pregnancy.

CDC has a comprehensive COVID-10 vaccine safety monitoring system in place to conduct post-marketing surveillance of COVID-19 vaccines following the issuance of emergency use authorizations (EUAs). The EUAs for the Pfizer-BioNTech and Moderna vaccines were issued on December 11 and 18, 2020, respectively. The presentation at the ACIP meeting on March 1st reported on vaccine safety data from several monitoring programs including v-safe, the Vaccine Adverse Event Reporting System (VAERS), and the Vaccine Safety Datalink (VSD) platform as noted below. Additional information about ongoing efforts to ensure COVID-19 vaccine safety can be found on websites maintained by CDC and FDA.

V-safe is a smartphone based “after vaccination health checker” where people who have received a COVID-19 vaccine can quickly tell CDC about any side effects they experienced. An analysis of safety data collected by the v-safe program during the first month of administration of the Pfizer-BioNTech and Moderna vaccines (December 14 – January 13) was published on February 19th in CDC Morbidity and Mortality Weekly Report (MMWR). Side effects (such as injection site pain, headache, fatigue, and muscle soreness) were similar for both the Pfizer-BioNTech and Moderna vaccines and consistent with those reported in the Phase 3 clinical trials.

The Vaccine Adverse Event Reporting System (VAERS) accepts reports from everyone regardless of the whether the vaccine caused the side effect or the level of clinical seriousness of the event. However, VAERS can rapidly detect safety “signals” and rare adverse events that warrant further investigation. Among the 105,000 COVID-19 vaccine-related adverse effects reported to VAERS as of February 16th, 94% were non-serious and 6% were serious (similar to experience with influenza vaccines). The most common side effects reported were headache, fatigue, fever, dizziness, chills, and pain at injection site, with no new safety concerns noted. Anaphylaxis continues to be a rare occurrence, with an estimated 2.5 cases per million doses administered for the Moderna vaccine, and 4.7 cases per million doses administered for the Pfizer-BioNTech vaccine as reported in the Journal of the American Medical Association .

CDC also utilizes Vaccine Safety Datalink (VSD), a collaborative project with nine health care organizations across the country to monitor possible adverse events when new vaccines are licensed (or authorized for emergency use such as for the current COVID-19 vaccines). Notably, CDC can assess if the rate of adverse events among vaccinated people is higher than among a comparison unvaccinated group; a higher rate of specific adverse events in vaccinated people may represent a “safety signal” that needs further attention. As of February 13, 2021, no such safety signals were detected among people vaccinated with either the Pfizer-BioNTech or Moderna vaccines as compared to the unvaccinated population.

More than 30,000 pregnant women who received either the Pfizer-BioNTech or Moderna COVID-19 vaccines have registered in the v-safe program. The side effect profile and adverse events observed among pregnant women did not indicate any safety issues, and most reports to the VAERS system among pregnant women involved non-pregnancy-specific side effects (local or systemic effects like injection-site pain, headache, fatigue, and muscle soreness). Pregnancy-specific adverse events such as miscarriage were within the known background rates for unvaccinated women.

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Moderna

Moderna COVID-19 Vaccine Updates

 

Summary of findings from Phase 3 trial evaluating the Moderna COVID-19 vaccine is available here. Data from this study were analyzed by the US Food and Drug Administration (FDA) before it issued an emergency use authorization for this vaccine.

Studies in Children

  • February 25, 2021: Moderna announced that it has completed enrollment of 3,000 adolescents aged 12-17 in a Phase 2/3 study evaluating the safety and efficacy of the mRNA-1273 vaccine in this age group. All participants have been recruited in the United States. This study is called the TeenCOVE study, after the original COVE study conducted in people age 18 and over. The company is planning to begin a third study (KidCOVE) focusing on children between the ages of 6 months and 11 years in the near future.

 

Development of Variant-Specific Vaccines

  • February 24, 2021: Moderna announced that it has completed manufacture of a vaccine candidate tailored to protect against the B.1.351 variant of the SARS-CoV-2 virus first identified in the Republic of South Africa. The variant-specific vaccine is called mRNA-1273.351. The Company has shipped doses of the variant-specific vaccine to the National Institute of Allergy and Infectious Disease (NIAID) at the National Institutes of Health (NIH). NIAID will perform a small clinical trial (Phase 1) to determine if the mRNA-1273.351 vaccine boosts immunity against the South African variant. Moderna envisions offering the mRNA-1273.351 vaccine as a booster for people who have already received the original vaccine or making a multivalent vaccine that would include the original vaccine and the variant-specific vaccine in a single shot. This type of multivalent (or combined) vaccine strategy is currently used for vaccines to prevent many other conditions, including influenza.


Efficacy Against Different Strains of SARS-CoV-2

  • January 26, 2021: Moderna announced results from a recently conducted in vitro study demonstrating that the Moderna vaccine, mRNA-1273, is likely to be effective in preventing infection from variant strains of the SARS-CoV-2 virus identified in the United Kingdom (called B.1.1.7) and South Africa (called B.1.351). Both of these variants of the SARS-CoV-2 virus have caused concern because they appear to be more contagious than the original virus. Although Moderna believes that the mRNA-1273 vaccine will provide protection against all variants of the SARS-CoV-2 virus identified to date, the recent study found that the mRNA-1273 vaccine, produces fewer neutralizing antibodies in response to the South African variant of the virus than in response to the original virus. This suggests than the vaccine may provide less protection against the South African variant of the virus. Therefore, the company has started to evaluate strategies to enhance vaccine efficacy. These include: determining if an additional booster dose of the mRNA-1273 vaccine increases the production of neutralizing antibodies against emerging virus strains including the B.1.351 variant and testing the efficacy of a modified vaccine (mRNA-1273.351) against the B.1.351 variant.

 Timeline for FDA Application and Availability of Vaccine to the Public

  • December 17, 2020: The US Food and Drug Administration (FDA) Vaccines and Related Biological Products Advisory Committee (VRBPAC) recommended that an emergency use authorization (EUA) be issued for the Moderna candidate vaccine, mRNA-123. The committee voted on the following question: “Based on the totality of scientific evidence available, do the benefits of the Moderna COVID-19 Vaccine outweigh its risks for use in individuals 18 years of age and older?” The vote was 20-Yes, 0-No, and 1-Abstention. (Note: Although Moderna recently started enrolling children age 12-17 into the trial, data from these participants are not yet available. That is why the question was limited to individuals age 18 or older.) It is likely that the FDA will issue the EUA tomorrow. The Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) is scheduled to meet on Saturday and Sunday of this week to vote on recommended uses of the Moderna COVID-19 vaccine under the EUA. The agenda for this meeting can be accessed here. The meeting will be live streamed and can be viewed here.
  • December 15, 2020: The US Food and Drug Administration (FDA) has released detailed findings from the Phase 3 trial of the Moderna candidate vaccine, mRNA-1273. An 84-page document prepared by Moderna is available here and a 7-page addendum to this document is available here.  A 54-page document prepared by the FDA is available here. On page 11 of this document the FDA states: “FDA has determined that the Sponsor has provided adequate information to ensure the vaccine’s quality and consistency for authorization of the product under an EUA” (Emergency Use Authorization). On page 12, the FDA states that the vaccine is proposed “for active immunization for the prevention of COVID-19 caused by SARS-CoV-2 in individuals 18 years of age and older.” We plan to report summarized safety and efficacy findings for the full sample and for different subgroups within the next few days.
  • November 30, 2020: Moderna announced that it plans to submit a request to the US Food and Drug Administration (FDA) today for an Emergency Use Authorization (EUA) for its candidate vaccine, mRNA-1273. In their primary efficacy analyses, 196 cases of laboratory-confirmed symptomatic COVID-19 occurred. Of these 185 occurred among people who received the placebo vaccine and 11 occurred among those tho received the mRNA-1273 vaccine, resulting in an estimate of vaccine efficacy of 94.1%. Of the 196 cases of symptomatic COVID-19 that occurred, 30 were classified as SEVERE COVID-19, all of which occurred in the placebo group.
  • November 11, 2020: Moderna reported that it has enough data for the first interim analysis from the Phase 3 trial of its experimental COVID-19 vaccine (mRNA-1273). It had submitted trial data to the independent board monitoring its trial, a sign that results could be announced shortly. The company said it expects this first interim analysis to include “substantially more than 53 cases,” which was the targeted trigger point for the analysis.
  • November 11, 2020: Dr. Anthony Fauci predicted that Moderna could have data from the Phase 3 trial of its COVID-19 vaccine (mRNA-1273) anywhere between “a couple of days” to “a little more than a week”.
  • October 22, 2020: According to a CNN report, Moderna’s president, Dr. Stephen Hoge, stated that “if all the stars align”, Moderna will apply for an emergency use authorization (EUA) for its COVID-19 vaccine (mRNA-1273) from the Food and Drug Administration (FDA) in early December 2020.

    Milestones to Reach Before FDA Submission

    53 study participants must develop laboratory-confirmed, symptomatic COVID-19.

    At least 40 of these 53 people (75%) must be in the control group (that is, they received a placebo vaccine).

    At least 15,000 study participants (50%) must be followed for at least 8 weeks after receiving their second dose of vaccine to assess possible side effects.

     
  • September 30, 2020: Moderna CEO, Stéphane Bancel told the Financial Times that Moderna will not seek an emergency use authorization for its COVID-19 vaccine (mRNA-1273) from the Food and Drug Administration (FDA) before November 25, 2020.

Interim Results

  • November 30, 2020: Moderna announced that it has completed the primary efficacy analysis for the Phase 3 study (known as the COVE study) testing its COVID-19 vaccine candidate, mRNA-1273.
    • A total of 196 people in the study developed laboratory-confirmed, symptomatic COVID-19. Of these, 185 had received the placebo vaccine and 11 had received the mRNA-1273 vaccine. Thus, they estimated that the vaccine reduces the risk of getting symptomatic COVID-19 by 94.1%.
    • In addition, a total of 30 people in the study developed severe COVID-19. All 30 had received the placebo vaccine.
    • No serious safety concerns have been reported.
    • Today, the Company will submit materials requesting a Emergency Use Authorization (EUA) for the mRNA-1273 vaccine from the United States (US) Food and Drug Administration (FDA). The Company expects these materials to be reviewed by the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) on December 17, 2020.
    • The Company expects to have about 20 million doses of the mRNA-1273 vaccine available in the United States by the end of 2020 and remains on track to manufacture 500 million to 1 billion doses globally in 2021.
  • November 16, 2020: Moderna announced results of the first interim analyses for its COVID-19 vaccine candidate, mRNA-1273. They reported that the vaccine was 94.5% effective in preventing laboratory-confirmed, symptomatic COVID-19. This study is known as the COVE study. More than 30,000 participants in the US are enrolled in the study. About half of these participants received the mRNA-1273 vaccine and the other half received a placebo vaccine.  95 participants in the study developed laboratory-confirmed COVID-19. Of these, 90 had received the placebo vaccine and 5 had received the mRNA-1273 vaccine. Of the 95 people in the study who developed COVID-19, 11 had severe COVID-19. All of the people who developed severe COVID-19 had received the placebo vaccine. No significant safety concerns were reported. The most common “severe” side-effects were: fatigue (9.7%), muscle pain (8.9%), and joint pain (5.2%). A “severe” side effect was defined as one that prevented a participant from doing routine daily activities on at least one day following an injection.
  • November 16, 2020: Moderna announced new data showing that its COVID-19 vaccine candidate, mRNA-1273, is more stable than originally estimated. The new data show that the vaccine remains stable:
    • At standard freezer temperatures (-4º F) for 6 months,
    • At standard refrigerator temperatures (36º to 46º F) for 30 days, and
    • At room temperature for up to 12 hours.

This better than expected stability will make it easier to distribute the vaccine to sites where it can be administered. It will also make it easier for doctors, nurses and pharmacists to store and administer the vaccine. In addition, the greater stability will likely result is less waste. The vaccine will come in vials than contain 5 doses. Once a vial is removed from the freezer, health care providers will have 30 days to use all 5 doses.

Continue reading “Moderna COVID-19 Vaccine Updates”

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BioNTech Moderna Pfizer Safety monitoring

Safety Monitoring Updates (February 15, 2021)

The U.S. Food and Drug Administration (FDA) granted Emergency Use Authorization (EUA) for the COVID-19 vaccines from Pfizer-BioNTech (December 11, 2020) and Moderna (December 18, 2020). At the January 27, 2021 meeting of the Center for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP), a member of CDC’s vaccine safety team provided a safety update on both vaccines based on information reported to CDC by both health care providers and people who had received one or two doses of the vaccines as of January 14, 2021. By this date, 23.4 million vaccine doses had been administered in the U.S. Overall, the safety profiles of COVID-19 vaccines are reassuring and consistent with safety data observed from the pre-authorization clinical trials.

CDC and the FDA use several mechanisms and databases for the ongoing collection and evaluation of COVID-19 vaccine safety data as these new vaccines are administered across the U.S.  A comprehensive, COVID-10 vaccine safety monitoring system was put in place by CDC to conduct post-marketing surveillance of COVID-19 vaccines following the issuance of EUAs. The presentation at the ACIP meeting on January 27 reported on vaccine safety data from several monitoring programs including v-safe, the Vaccine Adverse Event Reporting System (VAERS), and the Vaccine Safety Datalink (VSD) platform as noted below. In addition, Pfizer-BioNTech  and Moderna must submit periodic vaccine safety reports to the FDA  and report serious adverse events to VAERS.

The smartphone-based v-safe is an “after vaccination health checker” where people who have received a COVID-19 vaccine can quickly tell CDC about any side effects they experienced. Based on information reported to v-safe as of January 14, side effects (such as headache, fatigue and muscle soreness)  reported have been similar to those reported in the Phase 3 clinical trials.

Another mechanism to capture side effect information for vaccines is the Vaccine Adverse Event Reporting System (VAERS) which is co-managed by CDC and the FDA. VAERS accepts reports from everyone regardless of the whether the vaccine caused the side effect or the level of clinical seriousness of the event. However, VAERS can rapidly detect safety “signals” and rare adverse events that warrant further investigation.   The most reported adverse events for either the Pfizer-BioNTech or Moderna vaccines as of January 18 included headache, fatigue, fever, dizziness, chills, and pain, like the most frequent side effects reported in the v-safe platform.  Concerning the rare occurrence of anaphylaxis following vaccine administration, the available data indicate that 5.0 cases of anaphylaxis have occurred for every one million doses of the Pfizer-BioNTech vaccine administered and 2.8 cases have occurred for every one million doses of the Moderna vaccine administered.

CDC also utilizes the Vaccine Safety Datalink (VSD), a collaborative project with nine health care organizations across the country to monitor possible adverse events when new vaccines are licensed (or authorized for emergency use such as for the current COVID-19 vaccines). Notably, CDC can assess if the rate of adverse events among vaccinated people is higher than among a comparison unvaccinated group; a higher rate of specific adverse events in vaccinated people may represent a “safety signal” that needs further attention. As of January 16, 2021, no such safety signals were detected among people vaccinated with either the Pfizer-BioNTech or Moderna vaccines as compared to the unvaccinated population. While the Phase 3 studies of both vaccines noted a few more cases of Bell’s Palsy occurring in the vaccinated groups vs. the placebo arms, Bell’s Palsy did not represent a safety signal in the VSD analysis.  There were no reported cases of anaphylaxis in the VSD analysis among those vaccinated with either vaccine.

 

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Moderna

Novavax COVID-19 Vaccine Updates

Interim Study Findings and Timeline for FDA Application

  • January 28, 2021: Novavax presented information concerning the status of the Phase 3 study of its vaccine candidate, NVX-CoV2373, being conducted in the United States and Mexico. This study is testing a 2-dose regimen, with the doses administered 3 weeks apart. The Company plans to enroll a total of 30,000 study participants, with two-thirds of the participants receiving the NVX-CoV2373 vaccine.
    • As of January 27, 2021, a total of 16,748 people had been enrolled. The Company expects enrollment to be completed during the first half of February 2021 and that preliminary results may be available by April 2021.
    • The Company expects the NVX-CoV2373 vaccine to be approved for emergency use first in the United Kingdom (UK) based on findings from the study reported below. However, the Company is also discussing the types of data needed to obtain an emergency use authorization in other countries around the world, including the United States.
    • In the United States, the Food and Drug Agency could consider approving the NVX-CoV2373 vaccine for emergency use based on data from the UK study. In this case, emergency use authorization could be granted before the end of March 2021. 
    • Novavax is part of Operation Warp Speed and obtained $1.6 billion for vaccine research and the manufacture of 100 million vaccine doses.
  • January 28, 2021: Novavax announced the results of interim analyses from the Phase 3 study of its vaccine candidate, NVX-CoV2373, being conducted in the United Kingdom (UK). This study is testing a 2-dose regimen, with the doses administered 3 weeks apart. The study enrolled more than 15,000 people between the ages of 18 and 84.
    • In the interim analyses, the vaccine was nearly nearly 90% effective in preventing symptomatic COVID-19, beginning 7 days after the second dose. A total of 62 cases of symptomatic COVID-19 were observed (56 in the placebo group and 6 in the NVX-CoV2373 group). Only one participant developed severe COVID-19. This participant was in the placebo group.
    • Of the 62 cases observed, 32 were caused by the UK variant of the SARS-CoV-2 virus and 24 were caused by the original virus first identified in Wuhan, China. (In the remaining 6 cases, the virus has not been sequenced.) Vaccine efficacy was estimated at 95.6% against the original virus and 85.6% against the UK variant.
    • No safety concerns were identified.
    • The final analyses will be conducted when a total of 100 cases have been observed.
  • November 9, 2020: Novavax announced that its COVID-19 vaccine candidate, NVXCoV2373, has been granted Fast Track Designation by the US Food and Drug Administration (FDA). The Fast Track process is designed to streamline FDA review of new drugs and vaccines that may help treat or prevent a serious health problem. The goal is to get drugs and vaccines to patients as quickly as possible without compromising safety.

Participant Enrollment

  • October 27, 2020: Novavax announced that 5,500 people have been enrolled in the Phase 3 trial being conducted in the United Kingdom to test its COVID-19 vaccine candidate, NVXCoC2373. (For more information about this study, see Table 3 under Phase 3 studies.) The company increased the planned number of study participants from 9,000 to 15,000 and expects to have all participants enrolled by the end of November 2020. This is an event-driven study. The first interim analysis will be performed when at least 66 people in the study have developed laboratory-confirmed symptomatic COVID-19. With the increase in the number of study participants, the company expects to be able to conduct their first interim analysis as soon as the first quarter (January-March) of 2021.

Around the World

  • November 4, 2020: Novavax announced that it has signed a non-binding agreement with the Australian Government to supply 40 million doses of the company’s vaccine candidate, NVXCoC2373. The vaccine could be delivered as soon as the first half (January-June) of 2021. The agreement depends on whether the vaccine is shown to be safe and effective in ongoing Phase 3 trials and is approved for use by Australia’s Therepeutic Goods Administration (TGA). The TGA is equivalent to the Food and Drug Administration (FDA) in the United States. Novavax has established similar agreements with the governments in other countries, including: the United States, the United Kingdom, and Canada. They have also established agreements with partners to distribute the vaccine in Japan, South Korea, and India.
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AstraZeneca BioNTech COVID-19 Vaccine Janssen Johnson & Johnson Moderna Oxford Pfizer

Findings from Phase 1 and Phase 2 Trials

NOTE: The findings reported on this page are from early phase studies (Phases 1 and 2). These findings were used to justify going on to conduct the large Phase 3 studies required by the FDA before allowing a vaccine to be used in the United States. We only show studies that have led to Phase 3 studies.

BioNTech (Pfizer)

  • Safety and Immunogenicity of Two RNA-Based Covid-19 Vaccine Candidates.  Authors: Walsh EE, Frenck RW Jr, Falsey AR, Kitchin N, Absalon J, Gurtman A, Lockhart S, Neuzil K, Mulligan MJ, Bailey R, Swanson KA, Li P, Koury K, Kalina W, Cooper D, Fontes-Garfias C, Shi PY, Türeci Ö, Tompkins KR, Lyke KE, Raabe V, Dormitzer PR, Jansen KU, Şahin U, Gruber WC. Published in the New England Journal of Medicine on OCT-14-2020.
  • Phase I/II study of COVID-19 RNA vaccine BNT162b1 in adults.
    Authors: Mulligan MJ, Lyke KE, Kitchin N, Absalon J, Gurtman A, Lockhart S, Neuzil K, Raabe V, Bailey R, Swanson KA, Li P, Koury K, Kalina W, Cooper D, Fontes-Garfias C, Shi PY, Türeci Ö, Tompkins KR, Walsh EE, Frenck R, Falsey AR, Dormitzer PR, Gruber WC, Şahin U, Jansen KU. Published online in Nature on AUG-12-2020.

Moderna (BARDS, NIAID)

  • An mRNA Vaccine against SARS-CoV-2 – Preliminary Report. Authors: Jackson LA , Anderson EJ, Rouphael NG, Roberts PC, Makhene M , Coler RN, McCullough MP, Chappell JD, Denison MR, Stevens LJ, Pruijssers AJ, McDermott A, Flach B, Doria-Rose NA, Corbett KS, Morabito KM, O’Dell S, Schmidt SD, Swanson PA, Padilla M , Mascola JR, Neuzil KM, Bennett H, Sun W, Peters E, Makowski M, Albert J , Cross K, Buchanan W, Pikaart-Tautges R, Ledgerwood JE, Graham BS, Beigel JH, mRNA-1273 Study Group. Published in the New England Journal of Medicine on NOV-12-2020.

AstraZeneca (Iqvia)

Novavax (United States Department of Health and Human Services)

CanSino Biologics (Beijing Institute of Biotechnology)

Gamaleya Research Institute of Epidemiology and Microbiology, Health Ministry of the Russian Federation