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Janssen Johnson & Johnson

Johnson & Johnson (Janssen) COVID-19 Vaccine Updates

Summary of findings from Phase 3 trial evaluating the Janssen (Johnson & Johnson) 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.

 

Bottom Line About Rare Blood Clots With Johnson & Johnson (Janssen) COVID-19 Vaccine

    • The Johnson & Johnson (Janssen) COVID-19 vaccine appears to increase the risk of developing rare blood clots, combined with low platelet counts. The medical term for this condition is Thrombosis with Thrombocytopenia Syndrome (TTS). 
    • As of April 12, 2021, nearly 7 million people had received this vaccine in the United States.
    • As of April 21, 2021, 15 people who had received the vaccine developed TTS and 3 of these people died. 
    • The risk of developing TTS following vaccination is very low. For every 1 million women between 18 and 49 years old, about 7 developed TTS. The risk is even lower among older women and men of any age. 
    •  Analyses performed by scientists at the Center for Disease Control and Prevention (CDC) estimated that the risk of dying of COVID-19 is greater than the risk of developing TTS after receiving the Johnson & Johnson (Janssen) vaccine. Therefore, they continue to believe that the benefits of the vaccine outweigh the risks.
    • The small risk of TTS can be avoided by being vaccinated with either the Pfizer/BioNTech or Moderna vaccines. (No cases of TTS have been observed among people who have received the Pfizer/BioNTech or Moderna vaccines. Over 180 million doses of these vaccines have been administered in the US.)
    •  CDC encourages health care providers to talk to women between the ages of 18 and 49 about the risk of TTS with the Johnson & Johnson (Janssen) vaccine and to discuss the possibility of using one of the other approved COVID-19 vaccines instead. However, if a woman is unable to use either of the other vaccines or prefers a vaccine that only requires one shot, both the FDA and CDC considers the Johnson & Johnson (Janssen) vaccine safe and effective to use.
    • CDC continues to emphasize that vaccines save lives and encourages all adults to be vaccinated.

April 13 – April 23, 2021: On April 13th, the US Food and Drug Administration (FDA) recommended a pause in use of the Johnson & Johnson (Janssen) COVID-19 vaccine that received an Emergency Use Authorization in the US on February 27, 2021. As of April 12, 2021, more than 6.8 million doses of this vaccine had been administered. The pause was recommended in response to 6 cases of a rare type of blood clot (cerebral venous sinus thrombosis, CVST) combined with low platelet counts. The medical term for this condition is Thrombosis with Thrombocytopenia Syndrome (TTS). All six cases occurred in women between 18 and 48 years old within two weeks following vaccination with the Johnson & Johnson (Janssen) vaccine. 

A drug called heparin is usually used to treat blood clots. However, heparin can make TTS worse. The purpose of the pause was 2-fold. First, it allowed time for the FDA and Centers for Disease Control and Prevention (CDC) to make both patients and health care providers aware of this condition, including symptoms of a possible clot, the importance of early diagnosis and treatment, and treatments to implement (and those to avoid).

Currently, CDC recommends that people who receive the Johnson & Johnson (Janssen) vaccine, should be on the lookout for the following symptoms of a possible clot for three weeks after receiving the vaccine and should seek medical care right away if they develop any of these symptoms. The symptoms to watch for include: severe or persistent headaches or blurred vision, shortness of breath, chest pain, leg swelling, persistent abdominal pain, and easy bruising or tiny blood spots under the skin beyond the injection site

The second reason for the pause is that it gave the FDA and CDC time to review the cases that had been identified and determine the best way to proceed. Since April 13th, two emergency meetings of CDC’s Advisory Committee on Immunization Practices (ACIP) have been held. Both of these meetings were open to the public and live-streamed. Links to materials from these meetings are provided below. 

At the end of the meeting on April 23rd, the Committee recommended that use of the Johnson & Johnson (Janssen) vaccine resume in the United States without any age or sex restrictions. This recommendation was based on data concerning the risks and benefits associated with different vaccination strategies (e.g., limiting use of the vaccine to older adults), as well as the feasibility of implementing different strategies on a nationwide basis in the midst of the current global pandemic.

TTS is a very rare condition, affecting only 0.7 to 1.6 people per million in the US each year. Although the mechanism of action is not clear, it is likely that the Johnson & Johnson (Janssen) vaccine increases the risk of developing TTS. However, the likelihood of developing TTS following vaccination is very small. 

As of April 21, 2021, a total of 15 cases of TTS had been confirmed among the nearly 8 million people who had received the Johnson & Johnson (Janssen) vaccine. All of these cases occurred within about two weeks following vaccination. As of April 21st, 3 of the 15 people who developed TTS following vaccination had died and 4 remained hospitalized in an intensive care unit. (For comparison, no cases of TTS have been reported following the administration of the Pfizer/BioNTech or Moderna vaccines. As of April 21st, over 180 million doses of these vaccines had been administered in the US.) 

As shown in the table below, most of the 15 cases of TTS occurred among women between the ages of 18 and 49. In this group, 7.0 cases of TTS were reported for every 1 million doses of the Johnson & Johnson (Janssen) vaccine administered. Thus, even in this group, the likelihood of developing TTS following vaccination is very small.

 

Given this serious (but rare) risk, the question becomes whether the benefits associated with the Johnson & Johnson (Janssen) vaccine outweigh the risks. From a public health perspective, the answer is pretty clear. As shown in the table below, CDC scientists estimated that continuing to use the Johnson & Johnson (Janssen) vaccine for adults age 18 years and older would prevent 586 to 1,435 deaths due to COVID-19, while causing only 26 cases of TTS. The deaths prevented are the result of being able to vaccinate all interested adults more quickly than if only the Pfizer/BioNTech and Moderna vaccines were available.

CDC scientists also examined vaccine risks/benefits separately for younger women, older women, younger men, and older men. These analyses assumed that the people did not receive one of the other COVID-19 vaccines available in the US. As shown in the table below, the benefit/risk ratio was smallest for women in the younger age group.

At the end of the meeting on April 23rd, the Committee recommended that use of the Johnson & Johnson (Janssen) vaccine resume in the US without any age or sex restrictions. However, it was understood that the FDA would add a warning statement about the risk of TTS in materials distributed to patients and health care providers. In addition, CDC recommends that for females under the age of 50 health care providers discuss the option of receiving either the Pfizer/BioNTech vaccine or the Moderna vaccine instead of the Johnson & Johnson vaccine. They also emphasized that the risk of TTS is very low and that it is important for all individuals to be vaccinated. For individuals who are unable to receive one of the other vaccines or who cannot complete the 2-dose series required for both the Pfizer/BioNTech and Moderna vaccines, experts believe that the potential benefits of the Johnson & Johnson (Janssen) vaccine outweigh the known and potential risks. 

In conclusion, the ability of FDA and CDC scientists to quickly identify the very rare risk of TTS should reassure the public that surveillance systems such as the Vaccine Adverse Event Reporting System (VAERS) are working the way they should. Very rare adverse events are almost impossible to discover in clinical trials because they may not occur in even large trials involving tens of thousands of people. Once the possible risk of TTS was identified, the FDA and CDC worked together to implement a pause in use of the Johnson & Johnson (Janssen) vaccine, educate the public and health care providers about the potential risk of TTS, and implement an emergency review process by independent scientists before moving forward. This review process was transparent. Committee meetings were open to the public and all meeting materials remain available online. We applaud the FDA and CDC for their work to review the evidence and chart a course forward that is likely to prevent thousands of deaths over the coming months.

Other References:

Slides used in the scientific presentations made during the meeting on April 14th can be found here. The meeting can be viewed in full using the following links: Welcome & Coronavirus Disease 2019 (COVID-19) Vaccines and Public Comment & Vote. 

Slides used in the scientific presentations made during the meeting on April 23rd can be found here. It can be viewed in full using the following links: Welcome & Coronavirus Disease 2019 (COVID-19) Vaccines, Public Comment , and Janssen COVID-19 vaccine. 

The revised Fact Sheet for Healthcare Providers Administering Vaccine can be obtained here. This fact sheet now includes a warning about TTS.

A fact sheet for patients prepared by CDC can be found here.

A paper published in Morbidity and Mortality Weekly Report (MMRW) discussing the risk of TTS following administration of the Johnson & Johnson (Janssen) vaccine can be found here.

February 26, 2021: The Food and Drug Administration (FDA) Vaccines and Related Biological Products Advisory Committee (VRBPAC) recommended approval of an Emergency Use Authorization for the Janssen COVID-19 vaccine by a vote of 22-0 with no abstentions. Following the meeting, the FDA announced that it “has informed the sponsor that it will rapidly work toward finalization and issuance of an emergency use authorization. The agency has also notified our federal partners involved in vaccine allocation and distribution so they can execute their plans for timely vaccine distribution.”

Johnson & Johnson announced that it is able to begin delivery of the Janssen vaccine immediately after the EUA is issued and expects to deliver at least 20 million doses of the vaccine to the US by the end of March. Because this vaccine only requires one shot, that translates into 20 million people being fully vaccinated with the Janssen vaccine by the end of March. The Company plans to deliver a total of 100 million doses of the vaccine to the US by July 1, 2021.  

The Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) will meet on Sunday, February 28th to discuss recommendations concerning utilization and distribution of the Janssen vaccine. On Monday, March 1st, the ACIP will meet to discuss issues concerning COVID-19 vaccines more generally. The full agenda for the meetings on both Sunday and Monday can be found here. The meeting is open to the public and can be viewed via webcast. A link for the webcast can be found here.

February 25, 2021: The U.S. Food and Drug Administration (FDA) will discuss Johnson & Johnson’s (Janssen) request for an emergency use authorization (EUA) for the Company’s vaccine candidate, AD26.COV2.S at a meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) tomorrow (February 26, 2021). The meeting is scheduled to begin a 9:00 am EST. A draft agenda for the meeting can be found here. The meeting is open to the public and will be available to watch via the following links: 

February 24, 2021: The US Food and Drug Administration (FDA) has released detailed findings from the Phase 3 trial of the Johnson & Johnson (Janssen) vaccine candidate, Ad26.COV2.S (also known as, JNJ-78436735). The materials available include: a 119-page report prepared by Johnson & Johnson (Janssen), an 8-page addendum to the report, and a 62-page briefing document prepared by the FDA. On pages 12-13, the briefing document concludes: “As such, 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.” Per the briefing document (page 12), the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) will meet on Friday, February 26, 2021, “to discuss and provide recommendations on whether based on the totality of scientific evidence available, the benefits of the Janssen Ad26.COV2.S vaccine outweigh its risks for use in individuals 18 years of age and older.” This is the criterion used by the FDA when determining whether to grant an Emergency Use Authorization (EUA) for a vaccine. We plan to report summarized safety and efficacy findings from this study within the next few days.

February 4, 2021: The U.S. Food and Drug Administration (FDA) announced that it will discuss Johnson & Johnson’s request for an emergency use authorization (EUA) for the Company’s vaccine candidate, AD26.COV2.S at a meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) on February 26, 2021. Background material will be made available to the public by February 24th. We will provide links to those materials on this site as soon as they become available. The meeting will be livestreamed on the FDA’s YouTube, Facebook and Twitter channels. We will provide links to these channels for those who wish to watch.

February 4, 2021: Johnson & Johnson announced that they have submitted an application to the US Food and Drug Administration (FDA) requesting an emergency use authorization (EUA) for their vaccine candidate, AD26.COV2.S. The Company plans to be ready to ship doses of the vaccine immediately after receiving authorization from the FDA. The Johnson & Johnson vaccine is a potentially important addition to the other vaccines currently available in the United States because it is estimated to be 85% effective in preventing severe COVID-19 after a single dose and it can be shipped using normal distribution channels. The Company estimates that the vaccine can be stored a standard refrigerator temperatures (36-46º F) for up to three months. 

January 29, 2021: Johnson & Johnson announced findings from the ENSEMBLE trial evaluating the safety and efficacy of a single dose of their vaccine candidate, AD26.COV2.S. This study was conducted in several countries, including the United States and South Africa. In the United States, a single dose of this vaccine was found to be 72% effective in preventing moderate to severe COVID-19 beginning 28 days after vaccination. The effectiveness of the vaccine in preventing moderate to severe COVID-19 was 66% in Latin America and 57% in South Africa. (When averaged across all study sites the vaccine was found to be 66% effective in preventing moderate to severe COVID-19 and 85% effective in preventing severe COVID19. No deaths related to COVID-19 were reported in the vaccine group, whereas 5 COVID-19-related deaths occurred in the placebo group.) The Company also reported that the vaccine was well-tolerated and that no safety concerns were identified.

The ENSEMBLE trial included nearly 44,000 participants, with 34%  of participants over age 60. In their press release, the Company stated: “The study enrolled 44% (N=19,302) of participants in the United States, 41% (N=17,905) in Central and South America (Argentina, Brazil, Chile, Colombia, Mexico, Peru) and 15% (N=6,576) in South Africa.” The table below shows the race/ethnicity of study participants, both globally and for the US only.

Race/Ethnicity Globally US Only
White/Caucasian 59% 74%
Hispanic/Latinx 45% 15%
Black/African American 19% 13%
Native American 9% 6%
Asian 3% 1%

The Company reported that vaccine efficacy was mostly consistent across racial/ethnic and age groups, and across different variants of the virus and regions studied. In South Africa, about 95% of the COVID-19 cases observed among study participants were due to infection with a variant of the original SARS-CoV-2 virus from the B.1.351 lineage. It is unclear if the lower efficacy observed among South African participants was due to the vaccine providing less protection against these variants.

The Company is planning to file a request for an emergency use authorization (EUA) with the US Food and Drug Administration (FDA) in early February. This request will contain detailed findings from the study. Based on experience with the Pfizer-BioNTech and Moderna vaccines, we anticipate that the FDA Vaccines and Related Biological Products Advisory Committee (VRBPAC) will meet to review the EUA request in mid to late February. Materials submitted by Johnson & Johnson and the results of independent analyses conducted by FDA staff should be available to the public about two days before the VRBPAC meeting. 

If the EUA is granted, the Company expects to be able to meet all 2021 supply commitments. Notably, Johnson & Johnson was part of Operation Warp Speed and received $456 million for research to develop a vaccine and $1 billion to deliver 100 million vaccine doses.

In addition to the ENSEMBLE trial described above, Johnson & Johnson is conducting the ENSEMBLE 2 trial which is studying the safety and efficacy of a two-dose regimen of the AD26.COV2.S vaccine. Enrollment of study participants in ENSEMBLE 2 began on November 15, 2020.

December 17, 2020: Johnson & Johnson announced that enrollment in the ENSEMBLE study has been completed. This study is evaluating a single dose of the vaccine candidate AD26.COV2.S. About 45,000 people have been enrolled in the study. The company expects to be able to report interim findings from the study by the end of January 2021. However, this will depend on the rate at which people in the study get moderate/severe COVID-19. (The protocol for this study states that the first interim analyses will be performed when 20 people in the study have developed moderate/severe COVID-19. If the vaccine is effective, most of these cases will occur among people who received the placebo vaccine.)

If the data support the safety and efficacy of the AD26.COV2.S vaccine, the company expects to submit an application for an Emergency Use Authorization (EUA) to the US Food and Drug Administration in February. If a EUA is approved, AD26.COV2.S would become the third vaccine approved for use in the US and it would be the first to require only a single dose. It is important to remember, however, that no safety or efficacy data have yet been reported from the study. 

The Company intends to file for U.S. Emergency Use Authorization (EUA) in early February and expects to have product available to ship immediately following authorization. It expects to share more information on specifics of deployment as authorizations are secured and contracts are finalized. The Company’s anticipated manufacturing timeline will enable it to meet its 2021 supply commitments, including those signed with governments and global organizations.

November 15, 2020: Johnson & Johnson announced a second global Phase 3 study of its candidate vaccine, Ad26.COV2.S. This vaccine is also known as JNJ-78436735. This new study will evaluate a 2-dose vaccine regimen. The new study is called ENSEMBLE 2. See Table 1 under Phase 3 Studies for more details about the study.

October 23, 2020: Johnson & Johnson announced that it is preparing to resume recruitment in the United States in its Phase 3 trial of the candidate vaccine, Ad26.COV2.S. This vaccine is also known as JNJ-78436735. This trial is called the ENSEMBLE trial. The temporary pause was triggered when one study participant developed a serious medical event. The nature of the event was not disclosed due to patient privacy concerns. The company reported that no clear cause for the event could be identified and that there was no evidence that the vaccine caused the event. The Data Safety and Monitoring Board (DSMB) overseeing this trial determined that it was safe to resume recruitment. The U.S. Food and Drug Administration (FDA) agreed with this decision. The company is in discussion with other regulatory agencies around the world to resume the study in other countries.

October 12, 2020: Johnson & Johnson paused its Phase 3 trial of the investigational vaccine, Ad26.COV2.S. This trial is called the ENSEMBLE trial. Until the trial is resumed, no new participants will be enrolled in the trial and no participants in the trial will be vaccinated. In large clinical trials, it is not unusual for some study participants to experience major medical events and these events often happen by chance. When a serious adverse event happens, the trial is paused to allow the Data Safety and Monitoring Board (DSMB) overseeing the trial, as well as regulatory agencies like the FDA, an opportunity to review data from the trial and determine if it is safe to resume. In their press release, Johnson & Johnson also provided information to clarify the difference between a “Study Pause” and a “Regulatory Hold”.

September 23, 2020: Johnson & Johnson announced the launch of its Phase 3 trial of the investigational vaccine, Ad26.COV2.S. This trial is called the ENSEMBLE trial. In the press release, Paul Stoffels, M.D., Vice Chairman of the Executive Committee and Chief Scientific Officer, Johnson & Johnson stated:  “We greatly value the collaboration and support from our scientific partners and global health authorities as our global team of experts work tirelessly on the development of the vaccine and scaling up our production capacity with a goal to deliver a vaccine for emergency use authorization in early 2021.”

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AstraZeneca Oxford

AstraZeneca Oxford COVID-19 Vaccine (AZD1222) Updates

  • March 25, 2021 (Thursday): AstraZeneca announced results of the primary analysis of data from the Phase 3 clinical trial evaluating the Company’s COVID-19 vaccine candidate, AZD1222, being conducted in the United States, Peru, and Chile. A brief summary of the design of this study can be found in Table 1 on this website and the full study protocol can be found here.

    The primary efficacy analysis included data from 32,449 study participants. The study counted cases of laboratory-confirmed symptomatic COVID-19 that were diagnosed at least 15 days after participants received the second dose of the vaccine. A total of 190 cases were observed. The Company reported that the vaccine was 76% effective in preventing symptomatic COVID-19. The Company also reported that the vaccine was 100% effective in preventing severe COVID-19/hospitalization. A total of 8 cases of severe COVID-19 were observed – all among participants who received the placebo vaccine. No safety concerns were identified. These findings are quite similar to those reported on March 22, 2021.

    The Company noted that 14 additional cases of possible/probable COVID-19 have been identified among study participants. These cases are currently being reviewed by experts to determine if they meet the criteria for “laboratory-confirmed, symptomatic COVID-19”. The experts reviewing these cases do not which participants received the AZD1222 vaccine. After the status of these 14 cases is resolved, the estimate of vaccine efficacy could increase or decrease a few percentage points.

    AstraZeneca is likely to submit the full results of their primary analyses to the US Food and Drug Administration (FDA) as part of a request for an Emergency Use Authorization (EUA) for the AZD1222 vaccine within the next two weeks. The full report submitted to the FDA, as well as a report prepared by the FDA after reanalyzing study data, is likely to be made available to the public in late April.
  • March 23, 2021 (Tuesday):  The National Institutes of Allergy and Infectious Diseases (NIAID) made the following announcement: “Late Monday, the Data and Safety Monitoring Board (DSMB) notified NIAID, BARDA, and AstraZeneca that it was concerned by information released by AstraZeneca on initial data from its COVID-19 vaccine clinical trial. The DSMB expressed concern that AstraZeneca may have included outdated information from that trial, which may have provided an incomplete view of the efficacy data. We urge the company to work with the DSMB to review the efficacy data and ensure the most accurate, up-to-date efficacy data be made public as quickly as possible. Authorization and guidelines for use of the vaccine in the United States will be determined by the Food and Drug Administration and Centers for Disease Control and Prevention after thorough review of the data by independent advisory committees.”

    In clinical trials, a DSMB is an independent panel of experts responsible for ensuring the quality of study design and implementation, as well as the safety of study participants. All of the COVID-19 vaccine clinical trials funded by the US government use the same DSMB. This DSMB has access to all of the data being collected. The DSMB can quickly stop a study if a study participant experiences an adverse event, determine whether the participant received the experimental vaccine or the placebo vaccine, and communicate with health care providers treating the participant to determine if the adverse event was likely to be vaccine related. DSMBs help to minimize bias when interpreting study results because DSMB members receive no funding from the vaccine manufacturers.Dr. Anthony Fauci appeared on Good Morning America today and briefly explained the background behind the NIH announcement. Although Fauci stated that information in the AstraZeneca press release on Monday, March 22nd. might not be completely accurate, he continues to believe data for the vaccine look quite good. He also emphasized that the US Food and Drug Administration (FDA) carefully reviews all study data before issuing an Emergency Use Authorization for a vaccine. This serves as a reminder that many safeguards are in place in the US to prevent the authorization of vaccines that have not been shown to be safe and effective.

 

  •  March 23, 2021 (Tuesday): In response to the NIAID announcement described above, AstraZeneca announced that the interim findings reported on Monday, March 22nd. were based on data collected before February 17, 2021. The Company stated that they are now working on the primary analyses and intend to announce the results from those analyses within the next two days. The Company also stated that findings from the primary analyses appear to be consistent with the interim analyses reported on March 22nd., but that the primary analyses have not yet been finalized.The timing of the announcement yesterday (Monday, March 22, 2021) is perplexing. According to the study protocol, the Company planned to perform the first interim analyses when 75 cases of symptomatic COVID-19 had occurred. They planned to perform the final analyses when 150 cases had occurred. This is similar to the study design used by Pfizer/BioNTech, Moderna, and Janssen (Johnson & Johnson). However, these other companies released findings from their interim analyses within days of when they reached the number of cases needed. It is not clear why AstraZeneca took over a month. In addition, the interim analyses included 141 cases of symptomatic COVID-19, nearly the number required for the primary analyses. Given that the Company is in the midst of finalizing the primary analyses, one has to wonder why they issued the press release yesterday based on interim findings.

 

  • March 22, 2021 (Monday): AstraZeneca announced interim findings from a Phase 3 trial investigating the Company’s vaccine candidate, AZD1222. This study was conducted in the United States and involved over 30,000 participants. Two-thirds of the people in the study received two doses of the AZD1222 vaccine, administered 4 weeks apart. The remaining participants received two doses of a placebo vaccine. About 20% of the people in the study were age 65 years or older.The announcement stated that 141 cases of symptomatic COVID-19 had occurred among study participants. However, the announcement did not state how many of these cases were among those who received the AZD1222 vaccine. Instead, the announcement simply states that the vaccine was 79% effective in preventing symptomatic COVID-19. No participants who received the AZD1222 vaccine were hospitalized or developed severe COVID-19. However, the announcement does not indicate whether anyone who received the placebo vaccine developed severe disease or were hospitalized. This makes it difficult to interpret the Company’s claim of 100% efficacy in preventing severe disease/hospitalization. (A CNN report issued on Tuesday, March 23rd. indicated that during a media briefing Dr. Anthony Fauci said that five cases of severe disease/hospitalization were reported in the placebo group.)

    The Company reported that no safety concerns had been identified. They looked at the risk of thrombotic events (blood clots) in detail and found no evidence that the AZD1222 vaccine increases the risk of thrombotic events among 21,583 participants who had received at least one dose of the vaccine. However, it is not clear why this safety information was presented for 21,583 participants, whereas efficacy analyses were based on more than 30,000 participants.

    The announcement stated that the Company is continuing to analyze the data and plans to submit results of the forthcoming primary analyses to the US Food and Drug Administration (FDA) as part of a request for an Emergency Use Authorization for the AZD1222 vaccine in the next few weeks.
  • March 11-19, 2021: On March 11th., the Danish Medicines Agency launched an investigation of the AstraZeneca vaccine (AZD1222) after reports of thromboembolic events (blood clots) in some people who had received the vaccine. As a precaution, the Agency placed a hold on use of the vaccine in Denmark until the investigation was completed. Over the next few days, several other countries followed suit and the European Medicines Agency (EMA) launched an investigation. On March 18th., EMA issued a statement reporting the conclusions from its preliminary review. EMA’s safety committee reviewed instances of blood clots reported as of March 16th. By that date, over 20 million people in the United Kingdom and the European Economic Area had received the vaccine. A total of 469 thromboembolic events have been reported after vaccination. (This includes thromboembolic events observed in clinical trials.) This number is lower than what would be expected based on how often people in the general public experience thromboembolic events. Therefore, the Committee concluded that the AstraZeneca vaccine does not increase the overall risk of blood clots. However, some uncommon types of blood clots were observed. Specifically, 7 cases of blood clots in multiple blood vessels (disseminated intravascular coagulation, DIC) and 18 cases of clots in the vessels draining blood from the brain (CVST) have been reported.  Most of these occurred in women under 55. These rates are higher than what would be expected in this age group. The Committee concluded that although the benefits of the vaccine continue to outweigh the risks, patients should be informed about the “remote” possibility (about 1 in a million) of developing DIC or CVST following vaccination. Product information for patients and health care providers is being updated to include more information about this possible risk. The following information for patients is taken directly from the EMA statement:
      • COVID-19 Vaccine AstraZeneca is not associated with an increased overall risk of blood clotting disorders.
      • There have been very rare cases of unusual blood clots accompanied by low levels of blood platelets (components that help blood to clot) after vaccination. The reported cases were almost all in women under 55.
      • Because COVID-19 can be so serious and is so widespread, the benefits of the vaccine in preventing it outweigh the risks of side effects.
      • However, if you get any of the following after receiving the COVID-19 Vaccine AstraZeneca:
        • breathlessness,
        • pain in the chest or stomach,
        • swelling or coldness in a leg,1
        • severe or worsening headache or blurred vision after vaccination,
        • persistent bleeding,
        • multiple small bruises, reddish or purplish spots, or blood blisters under the skin,
      • please seek prompt medical assistance and mention your recent vaccination.

    The World Health Organization (WHO) also conducted a thorough review of thromboembolic events following vaccination with the AstraZeneca vaccine. They issued a statement on March 19th. that concurred with the EMA report, emphasizing that while it is not known whether the vaccine caused the rare cases of DIC and CVST, close monitoring of this possible risk is needed.

    Since these reports were issued, most countries have lifted the holds they put in place on using the AstraZeneca vaccine.

  • January 5, 2021: The Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom published the full Public Assessment Report for the AstraZeneca vaccine candidate, AZD1222. It can be accessed here.
  • December 30, 2020: The Medicines and Healthcare products Regulatory Agency (MHRA) in the United Kingdom granted temporary approval for the AstraZeneca vaccine candidate, AZD1222, to be used in the UK. The conditions for the approval are available here. The Information for Healthcare Professionals sheet contains information from the interim analyses reported on November 23, 2020. To the best of our knowledge, findings from the final efficacy analyses are not yet available.
  • November 30, 2020: Since AstraZeneca released the findings from the first interim analysis for its COVID-19 vaccine candidate, AZD1222, on November 23rd, it has been reported that the most promising finding announced by the company (90% efficacy among people who received a half dose of the vaccine, followed by a full dose one month later) occurred by mistake. No one in the study was supposed to receive a half dose of the vaccine before the full dose. A company spokesperson quoted by Reuters said that all participants were supposed to receive two full doses of the vaccine. However, that does not match the information the company provided in ClinicalTrials.Gov. According to ClinicalTrials.Gov, the study being conducted in the United Kingdom was designed to test: (1) a single full dose of the vaccine; (2) a single full dose of the vaccine, followed by a half dose “booster” 4-6 weeks later; (3) two full doses of the vaccine, separated by a 4-6 week period; and (4) a single half dose vaccine for children age 5-12. The study being conducted in Brazil was designed to test: (1) a single full dose of the vaccine and (2) two full doses of the vaccine, separated by a 4-12 week period.In addition, after the company released its interim findings, it was discovered that only participants who were 55 years old or younger had received the half dose vaccine. So, we have no way to know if the vaccine would have been equally effective in older adults, who are most likely to develop severe COVID-19.Astra-Zeneca did not initially disclose the dosing mistake, contending that it didn’t matter whether the dosing change was done on purpose or not. However, it does matter!Scientific studies are designed to test specific hypotheses. These hypotheses must be stated at the start of the study, before any data are collected. If the scientists discover other interesting things when they are conducting the study, they use these discoveries to develop new hypotheses and design new studies to test them. That is simply how the scientific process works. For this reason, the 90% efficacy reported for people who received the half dose vaccine should be viewed with skepticism.Notably, AstraZeneca has not published the full protocols for the studies being conducted in the United Kingdom or Brazil. Hopefully, they will make these available to the public soon. It would also be helpful to see the interim findings broken down by: (1) country (United Kingdom/Brazil), (2) age groups identified in the ClinicalTrials.Gov records for these studies, and (3) each dosing regimen examined.Despite these concerns, the interim analyses suggest that the 2 full dose regimen of AZD1222 may reduce the risk of developing symptomatic COVID-19 by 62%. This is better than the minimal threshold of 50% efficacy recommended by the Food and Drug Administration (FDA). Although this level of efficacy is lower than the vaccines developed by Pfizer and Moderna, the AstraZeneca vaccine can be stored at normal refrigerator temperatures (36-46° F) for at least six months and is less expensive to manufacture than the Pfizer and Moderna vaccines. Therefore, the AstraZeneca vaccine still has the potential to play a significant role in bringing the COVID-19 pandemic under control.
  • November 23, 2020: AstraZeneca announced results from an interim analysis of its COVID-19 vaccine candidate, AZD1222. The analysis included data from studies being conducted in the United Kingdom and Brazil. A total of 131 COVID-19 cases were included in the interim analysis. The company reported findings from two different dosing regimens. Among participants who received a half-dose of the vaccine, followed by a full dose one month later, vaccine efficacy was 90%. Among participants who received a full dose of the vaccine followed by a full dose one month later, vaccine efficacy was 62%. These findings are difficult to interpret because data from two countries were combined and different dosage regimens are being tested in these countries. It would be helpful to have the efficacy estimates reported separately for each country. In addition, in both countries, the studies are also evaluating the efficacy of a single dose regimen. No data concerning the effectiveness of the single dose regimen were reported.  
  • November 5, 2020: First results from Phase 3 trials for the AstraZeneca Oxford COVID-19 vaccine, AZD1222, are expected in the fourth quarter of 2020. (Note: This link opens to a slide presentation in pdf format. Information about AZD1222 appears on Slides 25 and 31.)
  • October 23, 2020: Clinical trials for the AstraZeneca Oxford COVID-19 vaccine candidate, AZD1222, resumed in the United States after the Food and Drug Administration (FDA) completed review of all safety data from trials being conducted around the world and determined that it was safe to resume the trial.
  • October 2, 2020: A Phase I/II clinical trial for the AstraZeneca Oxford COVID-19 vaccine candidate, AZD1222, resumed in Japan, with approval of the Japanese Pharmaceuticals and Medical Devices Agency (PMDA). Trials had previously been resumed in the United Kingdom, Brazil, South Africa, and India.
  • September 12, 2020: Clinical trials for the AstraZeneca Oxford coronavirus vaccine candidate, AZD1222, resumed in the United Kingdom after the Medicines Health Regulatory Authority (MHRA) determined that it was safe to do so.
  • September 9, 2020: A participant in a clinical trial for the AstraZeneca Oxford COVID-19 vaccine candidate, AZD1222, developed an unexplained illness. The illness was identified as part of standard procedures used in all clinical trials to ensure the safety of study participants. Immediately after the illness was identified, the developers voluntarily paused all clinical trials of the vaccine being conducted around the world. In an interview with NBC News, Dr. Francis Collins, Director of the National Institutes of Health, identified the illness as transverse myelitis and explained that the illness may not have been caused by the vaccine. In large clinical trials, illnesses often happen by chance. This pause in the study will allow data safety committees and regulatory agencies like the FDA an opportunity to review data from the trials to determine if it is safe to continue enrolling participants.
  • August 31, 2020: Enrollment began in the US Phase 3 trial for the AstraZeneca Oxford COVID-19 vaccine candidate, AZD1222.  Phase 3 trials of AZD1222 had begun previously in the UK, Brazil and South Africa.

Around the World

  • October 1, 2020: The European Medicines Agency (EMA) announced that it had started a “rolling review” of data from studies involving AstraZeneca’s vaccine candidate, AZD1222. The EMA is the equivalent of the Food and Drug Administration in the United States. According to the EMA announcement, “A rolling review is one of the regulatory tools that EMA uses to speed up the assessment of a promising medicine or vaccine during a public health emergency. Normally, all data on a medicine’s effectiveness, safety and quality and all required documents must be submitted at the start of the evaluation in a formal application for marketing authorisation. In the case of a rolling review, EMA’s human medicines committee (CHMP) reviews data as they become available from ongoing studies, before a formal application is submitted. Once the CHMP decides that sufficient data are available, the formal application should be submitted by the company. By reviewing the data as they become available, the CHMP can reach its opinion sooner on whether or not the medicine or vaccine should be authorised.”
Categories
Bharat Biotech

Bharat Biotech COVID-19 Vaccine (Covaxin) Updates

  • March 3, 2021: Bharat Biotech announced interim findings from  the Phase 3 study testing the Company’s COVID-19 vaccine candidate, COVAXIN (also known as BBV152). This is an inactivated vaccine that requires two doses, separated by a 4-week period.

    • A total of 25,800 people took part in the study. All study participants were recruited in India. More information about the study can be in Table 1 on this website.
    • 43 people in the study developed laboratory-confirmed, symptomatic COVID-19 beginning 14 days after they received the second dose of the vaccine. Of these, 36 had received the placebo vaccine and 7 had received COVAXIN. Thus, the vaccine is estimated to reduce the risk of getting symptomatic COVID-19 by 80.6%.
    • No serious safety concerns have been reported.
    • Going forward, the Company plans to conduct final analyses when a total of 130 people in the study have developed COVID-19. 
  • January 3, 2021: Bharat Biotech announced that the Company’s COVID-19 vaccine candidate, COVAXIN (also known as BBV152), has been approved for emergency use in India. Approval was based on promising safety and immune response (immunogenicity) findings from early stage (Phase 1 and 2) studies involving about 1,000 study participants. Findings from these studies can be accessed using two links below.Safety and immunogenicity clinical trial of an inactivated SARS-CoV-2 vaccine, BBV152 (a phase 2, double-blind, randomised controlled trial) and the persistence of immune responses from a phase 1 follow-up report
    A Phase 1: Safety and Immunogenicity Trial of an Inactivated SARS-CoV-2 Vaccine-BBV152   
Categories
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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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.
Categories
Gamaleya Sputnik V

Sputnik V Vaccine Updates

Interim Findings

  • November 24, 2020: The Gamaleya Center and the Russian Direct Investment Fund announced that their COVID-19 vaccine candidate is 91.4% effective in preventing COVID-19 starting 28 days after participants receive the first dose of the vaccine (7 days after the second dose). The data reported included a total of 18,794 study participants. Of these, 14,095 received the Sputnik V vaccine and 4,699 received a placebo vaccine. A total of 39 cases of laboratory-confirmed COVID-19 were identified, 8 among people who received the Sputnik V vaccine and 31 among people who received a placebo vaccine. In addition, the vaccine is over 95% effective when only counting cases beginning 42 days after the first dose (21 days after the second dose). These findings are consistent with immunity from COVID-19 increasing over time following the second vaccination. However, we still do not know how long immunity lasts. No serious safety concerns have been reported.
    • Several unanswered questions remain:
      1. We do not know how long immunity lasts.
      2. The investigators appear to be including all cases of laboratory-confirmed COVID-19, not just those that cause the patient to have symptoms. This is different than studies being conducted in the United States, where the primary focus is on symptomatic COVID-19. Thus, we do not know if the Sputnik V vaccine reduces the risk of developing symptomatic COVID-19.
      3. We do not know if the Sputnik V vaccine reduces the risk of developing severe COVID-19, being hospitalized, or dying.
      4. We do not believe that the developers of this vaccine have made their full study protocol available online. This is important because all analyses conducted should be planned from the beginning of the study. Publishing the protocol helps to ensure that the developers do not change their analyses in a way that biases their findings.
  • November 11, 2020: The Gamaleya Center and the Russian Direct Investment Fund announced results from the first interim analysis of their COVID-19 vaccine candidate, Sputnik V. They report that the vaccine is 92% effective in preventing COVID-19 starting 21 days after the first dose of the vaccine. The trial included data from over 16,000 study participants. Among these individuals, a total of 20 people developed laboratory-confirmed COVID-19. The announcement does not say how many of these 20 people had received the Sputnik V vaccine.
    • Several unanswered questions remain:
      1. We do not know how long immunity lasts.
      2. The investigators appear to be including all cases of laboratory-confirmed COVID-19, not just those that cause the patient to have symptoms. This is different than studies being conducted in the United States, where the primary focus is on symptomatic COVID-19. Thus, we do not know if the Sputnik V vaccine reduces the risk of developing symptomatic COVID-19.
      3. We do not know if the Sputnik V vaccine reduces the risk of developing severe COVID-19, being hospitalized, or dying.
      4. We do not believe that the developers of this vaccine have made their full study protocol available online. This is important because all analyses conducted should be planned from the beginning of the study. Publishing the protocol helps to ensure that the developers do not change their analyses in a way that biases their findings.

Manufacturing

  • November 27, 2020: The Russian Direct Investment Fund and Hetero (a major generic pharmaceutical company in India) have reached an agreement to make 100 million doses of the Sputnik V vaccine per year beginning in 2021.
  • November 13, 2020: The Russian Direct Investment Fund has reached an agreement with GL Rapha (a major bio-tech company in South Korea) to make 150 million doses of the Sputnik V vaccine per year, beginning in December 2020. The vaccine will be distributed globally.
  • September 30, 2020: The Russian Direct Investment Fund has reached an agreement with Pharco (a major pharmaceutical group in Egypt) to supply 25 million doses of the Sputnik V vaccine to Egypt. This will give 25% of the population of Egypt access to this vaccine.
  • September 29, 2020: The Russian Direct Investment Fund has reached an agreement with Trinity Pharmaceutical (a major pharmaceutical distributor in Nepal) to supply 25 million doses of the Sputnik-V vaccine to Nepal. This will give 90% of the population of Nepal access to this vaccine.
  • September 25, 2020: The Russian Direct Investment Fund has reached an agreement with LAXISAM (a major pharmaceutical company in the Republic of Uzbekistan) to supply up to 35 million doses of the Sputnik V vaccine to Uzbekistan in 2020-2021.
  • September 16, 2020: The Russian Direct Investment Fund (RDIF) has reached an agreement with Dr. Reddy’s Laboratories (a major pharmaceutical company in India) to cooperate on clinical trials and distribution of the Sputnik V vaccine in India. After the vaccine is approved for use in India, the RDIF will supply 100 million doses of the vaccine, potentially beginning in December 2020.
  • September 11, 2020: The Russian Direct Investment Fund has reached an agreement with the State of Bahia (Brazil) to supply up to 50 million doses of the Sputnik V vaccine, potentially beginning in November 2020. The agreement assumes that the vaccine is approved for use in Brazil by regulatory agencies.
  • September 9, 2020: The Russian Direct Investment Fund has reached an agreement with Landsteiner Scientific pharmaceutical company to supply up to 32 million doses of the Sputnik V vaccine to Mexico. This will give 25% of the people in Mexico access to the Sputnik V vaccine.
  • August 26, 2020: The Russian Direct Investment Fund has reached an agreement with SK-Pharmacy (a pharmaceutical company in Kazakhstan) to supply the Sputnik V vaccine to Kazakhstan. The press release does not say how many doses will be provided.
Categories
BioNTech Pfizer

BioNTech SE (Pfizer) COVID-19 Vaccine Updates

Summary of findings from the Phase 3 trial evaluating the Pfizer-BioNTech 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 and Adolescents

April 9, 2021: Pfizer and BioNTech submitted a request to the US Food and Drug Administration (FDA) asking that the Emergency Use Authorization (EUA) for their COVID-19 vaccine (BNT162b2) be expanded to allow the vaccine to be used for adolescents 12 to 15 years of age. As of April 27, 2021, the FDA has not scheduled a meeting of the Vaccine and Related Biological Products Advisory Committee to review this request. The FDA required this Committee to hold a public meeting to review the original EUA requests for each of the currently authorized vaccines (Pfizer/BioNTech, Moderna, and Janssen), but has not been required to meet to review EUA amendments (e.g., requests to change the number of doses contained in a vial). However, this is the first EUA amendment requesting authorization to expand age eligibility for the vaccine.

March 31, 2021: Pfizer and BioNTech announced findings from their Phase 3 clinical trial involving adolescents between the ages of 12 and 15 years. This trial enrolled 2,260 adolescents in the United States. Adolescents were randomly assigned to receive either the BTN162b2 vaccine or a placebo vaccine. Among the 1,129 adolescents who received the placebo vaccine, 18 developed COVID-19. In contrast, among the 1,131 adolescents who received the BTN162b2 vaccine, none developed COVID-19. The investigators also measured the level of SARS-CoV-2-neutralizing antibodies produced after vaccination. These antibodies protect against infection with the SARS-CoV-2 virus that causes COVID-19. On average, the level of antibodies produced was similar to that previously observed in older teens and young adults between the ages of 16 and 25 years. This provides additional confidence in vaccine efficacy. Finally, no safety concerns were identified and the side effects observed were similar to those previously reported by older teens and young adults.

The Companies also reported on the status of their global Phase 1/2/3 study that is examining the effects of the BTN162b2 vaccine among children aged 6 months to 11 years. Investigators began enrolling children between the ages of 5 and 11 years into this study during the last week of March and plan to begin enrolling younger children in April.

Updated Findings From Adult Study

April 1, 2021: Pfizer and BioNTech announced updated findings from the Phase 3 clinical trial investigating their COVID-19 vaccine, BNT162b2. Data collected through March 13, 2021 were included in the analyses. The trial included 46,307 participants. Approximately half of the participants received the BTN162b2 vaccine (2 doses administered 3 weeks apar); while the remaining participants received a placebo vaccine. A total of 927 laboratory-confirmed cases of symptomatic COVID-19 were observed. Of these, 850 cases occurred among participants who received the placebo vaccine and 77 occurred among those who received the BTN162b2 vaccine. Thus, the BTN162b2 vaccine was estimated to reduce the risk of getting COVID-19 by 91%. In other analyses, the BTN162b2 vaccine was estimated to be between 95% and 100% effective in reducing the risk of SEVERE COVID-19. 

Analyses were also conducted to determine if the BTN162b2 vaccine was effective in preventing COVID-19 caused by the variant of the virus first identified in South Africa (B.1.351). A total of 800 participants were enrolled in South Africa. Nine cases of COVID-19 were observed among South African participants. All of these cases occurred in the placebo group and six were caused by the B.1.351 variant. Thus, these results suggest that the vaccine is effective in preventing COVID-19 caused by the B.1.351 variant. 

Finally, these analyses included 12,000 participants who had been followed for at least six months following their second dose of the vaccine. No serious safety concerns have been observed. 

Effectiveness When Used in a Nationwide Immunization Program

March 11, 2021: The Israel Ministry of Health (MoH) and BioNTech announced findings from an observational study examining the extent to which the Pfizer-BioNTech COVID-19 vaccine (BTN162b2) reduces the risk of developing COVID-19 when administered as part of a nationwide immunization program. Israel launched its national vaccination program on December 6, 2020. The program targeted individuals age 16 years or older. This target group includes about 6.4 million people. The MoH used public health surveillance data collected between January 17 and March 6, 2021 to determine the date individuals received the BTN162b2 vaccine and the results of all COVID-19 tests performed. During this time period, the BTN162b2 vaccine was the only vaccine approved in Israel for the prevention of COVID-19 and the dominant strain of the SARS-CoV-2 virus was the variant first identified in the United Kingdom (B.1.1.7). 

The investigators reported that the vaccine reduced the risk of developing symptomatic COVID-19, hospitalizations, and deaths by at least 97%. 

The investigators also reported that the vaccine reduced the risk of developing asymptomatic SARS-CoV-2 infection by 94%.  This is important to prevent spread of the SARS-CoV-2 virus by people who are infected but who do not experience symptoms. 

Finally, the investigators reported that more than 80% of the positive tests involved the B.1.1.7 variant, providing evidence that the BTN162b2 vaccine is effective against this variant as well as the original SARS-CoV-2 virus first identified in Wuhan, China.

Efficacy Against Different Strains of SARS-CoV-2

  • January 20, 2021: Pfizer announced results from a recently conducted in vitro study demonstrating that the Pfizer-BioNTech vaccine, BTN162b2, is likely to be effective in preventing infection from the mutant strain of the SARS-CoV-2 virus first identified in the United Kingdom. This strain, called B.1.1.7, has caused concern because it appears to be more contagious than the original SARS-CoV-2 virus. The press release includes a link to a report describing the methods used in this study as well as study findings.

Post-Marketing Surveillance

  • January 19, 2021: The Norwegian Medicines Agency (NOMA) issued a statement about the 23 deaths that occurred among severely frail nursing home residents following coronavirus vaccination. The statement stresses that: “Fatal incidents among these severely frail patients following vaccination do not imply a causal relationship between COVID-19 vaccination and death.”  As of January 18, 2021, 48,680 people in Norway have been vaccinated. Many of those vaccinated are nursing home residents. This group was prioritized to receive the vaccine, because nursing home residents are at greatest risk for severe COVID-19. In the statement, Dr. Sara Viksmoen Watle, Senior Physician at the Norwegian Institute of Public Health explained:

“When we vaccinate the eldest and sickest who often have several underlying conditions we expect high mortality in this population. Hence, we also expect deaths following vaccination. We do not yet know if these deaths are due to the vaccine or other causes, but we cannot exclude that common side effects may have led to a more severe course for some patients. The 23 deaths occurred within six days after vaccination. We will examine these events in relation to the expected number of deaths among the nursing home populations. The Norwegian Medicines Agency and the Norwegian Institute of Public Health are now carrying out in-depth analyses. So far, there are no statistical analyses that indicate that coronavirus vaccination has had an increased risk of death among those vaccinated.” 

  • January 15, 2021: The Norwegian Medicines Agency (NOMA) has advised doctors in Norway to carry out extra evaluation of very sick, elderly patients before administering the Pfizer-BioNTech vaccine. This advisory was in response to the deaths of 23 frail, elderly nursing home residents in Norway who died within 6 days of receiving the vaccine. NOMA has investigated 13 of these deaths and found that vaccine side effects such as fever and diarrhea may have contributed to the deaths. They emphasize that these types of side effects are NOT dangerous for younger, fitter people. More information can be found in: a 1-page paper published in the British Medical Journal and a NOMA report issued on January 15, 2021.

The Pfizer-BioNTech vaccine is currently the only COVID-19 vaccine approved for use in Norway and more than 20,000 doses have been administered over the past few weeks. Nursing home residents have been prioritized to receive the vaccine, because they are at greatest risk for severe COVID-19. An average of 400 nursing home residents die each week in Norway. Therefore, the reported deaths following vaccination could be coincidental. Norway is continuing to monitor reports of adverse effects following vaccination, but has not changed its vaccination strategy.

Timeline for FDA Application and Availability of Vaccine to the Public

  • December 12, 2020: The Centers for Disease Control and Prevention (CDC) Advisory Committee on Immunization Practices (ACIP) will meet today to vote on recommended uses of the Pfizer-BioNTech COVID-19 vaccine candidate, BTN162b2, under the emergency use authorization (EUA) issued yesterday by the US Food and Drug Administration (FDA). The meeting is scheduled to begin at 11:00 am (EST) and adjourn at 3:00 pm (EST). The full agenda can be accessed here. The meeting is being live streamed and can be viewed here.
  • December 11, 2020: The US Food and Drug Administration (FDA) issued an emergency use authorization (EUA) for the Pfizer-BioNTech COVID-19 vaccine candidate, BTN162b2. This authorization allows the vaccine to be used in individuals 16 years of age and older. As part of the EUA, Pfizer is required to submit a safety report each month that includes information about adverse events and newly identified safety concerns. If these reports are made available to the public, we will provide information from the reports on this site. The FDA Fact Sheet for healthcare providers administering the vaccine can be accessed here and a Fact Sheet for patients and caregivers can be accessed here.
  • December 10, 2020: The US Food and Drug Administration (FDA) Vaccines and Related Biological Products Advisory Committee (VRBPAC) recommended that an emergency use authorization be issued for the Pfizer-BioNtech candidate vaccine, BNT162b2. The committee voted on the following question: “Based on the totality of scientific evidence available, do the benefits of the Pfizer-BioNTech COVID-19 Vaccine outweigh its risks for use in individuals 16 years of age and older?” The vote was 17-Yes, 4-No, and 1-Abstention. Those who voted No were concerned that there is limited information available for use of the vaccine in adolescents age 16 and 17. It is likely that the FDA will issue the EUA within the next few days.
  • December 8, 2020: The US Food and Drug Administration (FDA) has released detailed findings from the Phase 3 trial of the Pfizer-BioNtech candidate vaccine, BNT162b2. A 92-page document prepared by Pfizer is available here. A 53-page document prepared by the FDA is available here. On page 11 of this document the FDA states: “As such, 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 16 years of age and older.” We plan to report summarized safety and efficacy findings for the full sample and for different subgroups (based on age, gender, race, country) within the next few days.
  • November 20, 2020: Pfizer 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, BNT162b2. If the FDA approves the EUA, the company said that it may be possible to start vaccinating high-risk people in the US by the middle to end of December 2020. The FDA has stated previously that it plans to have an open meeting of the FDA’s Vaccines and Related Biological Products Advisory Committee (VRBPAC) before approving a EUA for any COVID-19 vaccines. This committee meeting is planned for Dec. 10, 2020. The FDA plans to make background materials for this meeting available on December 8, 2020. We anticipate that these materials will include much more detailed findings from the Phase 3 study testing BNT162b2. In addition, the Centers for Disease Control and Prevention (CDC) has scheduled a meeting for its Advisory Committee on Immunization Practices (AICP) on November 23, 2020. This Committee develops recommendations for the use of vaccines in the US. However, it does not have the authority to issue a EUA.
  • November 9, 2020: Pfizer announced that it expects to submit for an Emergency Use Authorization (EUA) for their mRNA-based COVID-19 vaccine candidate, BNT162b2, from the Food and Drug Administration (FDA) in the third week of November. This is based on when they expect to have two months of follow-up safety data for at least 15,000 study participants, as required by the FDA.
  • November 9, 2020: Pfizer currently expects to manufacture up to 50 million vaccine doses for the global market by the end of 2020 and up to 1.3 billion doses by the end of 2021. This assumes that the vaccine is approved for marketing by regulatory agencies (such as the Food and Drug Administration (FDA) in the US and the European Medicines Agency (EMA) in Europe).
  • October 19, 2020: According to the Pfizer COVID-19 website, the company expects to manufacture 100 million vaccine doses for the global market by the end of 2020 and up to 1.3 billion doses by the end of 2021. This assumes that the vaccine is approved for marketing by regulatory agencies (such as the Food and Drug Administration (FDA) in the US and the European Medicines Agency (EMA) in Europe).
  • October 16, 2020: In an open letter, Pfizer Chairman and CEO Albert Bourla announced that Pfizer may know whether their vaccine is effective by the end of October. The exact date is uncertain because the data from the study will not be analyzed until 32 study participants have gotten laboratory confirmed symptomatic COVID-19. According to the study protocol, the vaccine would be considered effective if at least 26 of these 32 participants were in the control group.

    Milestones to Reach Before FDA Submission

    Expected Date When Milestone Will Be Reached

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

    End of October

    At least 26 of these 32 people (81%) must be in the control group (that is, they received a placebo vaccine).

    End of October

    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.

    Third Week of November

    Manufacturing data must demonstrate the quality and consistency of the vaccine production process.

    Before the Third Week of November

 

Vaccine Authorized for Use in the UK

  • December 2, 2020: The Commission on Human Medicines (CHM) in the United Kingdom (UK) approved emergency use of Pfizer’s vaccine candidate, BNT162b2, following review by the Medicines and Healthcare products Regulatory Agency (MHRA). The CHM also released a document for health care providers in the UK that contains information from clinical trials testing BNT162b2. As reported previously, among study participants who were age 16 or older, a total of 170 developed laboratory-confirmed symptomatic COVID-19.  Of these 170 study participants, 162 had received the placebo vaccine and 8 had received BNT162b2. Thus, the vaccine appears to reduce the risk of getting COVID-19 by 95.0% (95% confidence interval 90.3% to 97.6%). The vaccine appears to be equally effective in adults age 65 and older, who made up 21.8% of the sample. However, it is not clear if people over the age of 85 were enrolled in the study. (By study design, only cases of COVID-19 that occurred at least 7 days following receipt of the second vaccine dose were counted. This allowed time for immunity to develop following vaccine administration.)

    Safety data are based on 19,067 study participants (9,531 who received the BNT162b2 vaccine and 9,536 who received the placebo vaccine). The most common side effects were: pain at the injection site (> 80%), fatigue (> 60%), headache (> 50%), muscle pain (> 30%), chills (> 30%), joint pain (> 20%), and fever (> 10%). The intensity of these side effects was usually mild or moderate and resolved within a few days after having the vaccine administered.

    • Pregnancy, Breast-feeding:  Due to the lack of data, it was originally recommended that the BNT162b2 vaccine not be administered during pregnancy. However, this recommendation was changed. The current professional labeling states that use of this vaccine during pregnancy “should only be considered when the potential benefits outweigh any potential risks for the mother and foetus.”
    • Children: Data have only been reported for study participants who were age 16 or older. The vaccine is currently being studied in children age 12-16, so more data may be released soon.
    • Duration of Immunity: We also do not know how long protection from COVID-19 will last after BNT162b2 is administered.

Results from Primary Efficacy Analyses

  • November 20, 2020: Pfizer submitted materials to the US Food and Drug Administration requesting an emergency use authorization for it COVID-19 vaccine candidate, BNT162b2. The FDA announced that the materials will be reviewed by its Vaccines and Related Biological Products Advisory Committee (VRBPAC) on December 10, 2020. This meeting will be live streamed on the agency’s YouTube, Facebook and Twitter channels. The FDA plans to make background materials for this meeting available on December 8, 2020. We anticipate that these materials will include much more detailed findings from the Phase 3 study testing BNT162b2.
  • November 18, 2020: Pfizer announced that it has completed the primary efficacy analyses of data from the Phase 3 study testing its COVID-19 vaccine candidate, BNT162b2. As planned before the start of data collection, the primary efficacy analyses were conducted after 164 study participants developed laboratory confirmed symptomatic COVID-19. The company reported that a total of 170 people had reached this study endpoint. Of these, 162 had received the placebo vaccine and 8 had received the BNT162b2 vaccine. Thus, they estimated that the vaccine is 95% effective in preventing COVID-19. The vaccine also appears to help prevent severe COVID-19. A total of 10 people in the study developed severe COVID-19. Of these, 9 had received the placebo vaccine. The company reported no serious safety concerns. The most common  “severe” side-effects reported were: fatigue (3.8%) and headache (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. Finally, the company reported that the findings were similar across groups that differed in age, gender, race, and ethnicity. Although these findings are very promising, several important questions remain. For example, we do not know if the vaccine reduces the risk of hospitalization or death. We also do not know if the vaccine prevents asymptomatic COVID-19. This is important because individuals with asymptomatic COVID-19 can infect others who can then develop more serious disease. We also do not know how long protection lasts and only limited data are available concerning side-effects the vaccine may have. Finally, data reported by the company still needs to be reviewed by experts who are not involved with the study

Interim Results

  • November 9, 2020: Pfizer announced that its mRNA-based COVID-19 vaccine candidate, BNT162b2, has demonstrated over 90% efficacy in preventing laboratory-confirmed symptomatic COVID-19 among participants with no prior history of SARS-CoV-2 infection. These results are based on planned interim analyses. A total of 94 study participants have developed laboratory-confirmed, symptomatic COVID-19 to date. (Cases of COVID-19 are only counted if they occurred at least one week after the second dose of the vaccine was administered. This gives the vaccine time to work.) The company reported that no serious safety concerns have been observed in the trial. We will provide more detailed information as soon as it is available to the public. The company will conduct their final efficacy analyses when at least 164 study participants have developed laboratory confirmed cases of COVID-19.  The company also plans to conduct analyses to see if the vaccine helps prevent severe COVID-19. Although these findings are very promising, several important questions remain. For example, we do not know if the vaccine reduces the risk of severe COVID-19, hospitalization, or death. We also do not know if the vaccine prevents asymptomatic COVID-19. This is important because individuals with asymptomatic COVID-19 can infect others who can then develop more serious disease. We also do not know how long protection lasts and only limited data are available concerning side-effects the vaccine may have. Finally, data reported by the company still needs to be reviewed by experts who are not involved with the study.

Participant Enrollment

  • November 9, 2020: Pfizer announced that the trial of their mRNA-based COVID-19 vaccine candidate, BNT162b2, has enrolled 43,538 participants and 38,955 have received the second dose of the vaccine, which is given three weeks after the first dose. About 30% of participants recruited in the United States have racially and ethnically diverse backgrounds. The Pfizer COVID-19 vaccine website provides more information about the race/ethnicity of study participants and the percentage of participants between the ages of 56 and 85 years.
  • October 19, 2020: According to the Pfizer COVID-19 vaccine website, they have enrolled 39,862 study participants in their clinical trial to date and 34,601 of these participants have received the second dose of vaccine. (Note: The vaccine being tested in this study requires 2 doses, given 3 weeks apart.) The Pfizer COVID-19 vaccine website includes a table showing the race/ethnicity of study participants and the percentage of participants between the ages of 56 and 85 years.
  • October 13, 2020: Pfizer announced that it has gotten approval from the Food and Drug Administration (FDA) to enroll children as young as 12 years old in their clinical trial.
  • September 12, 2020: Pfizer announced that it plans to increase enrollment in their clinical trial from about 30,000 study participants up to about 44,000 participants. They also plan to expand the eligibility criteria for the study to include adolescents who are 16 or 17 years old.

 

Around the World

  • November 20, 2020: Pfizer announced that several countries have started a rolling review of its vaccine candidate, BNT162b2. These include: Australia, Canada, Japan, the European Union, and the United Kingdom.
  • October 6, 2020: The European Medicines Agency (EMA) announced that it had started a “rolling review” of data from studies involving Pfizer’s vaccine candidate, BNT162b2. The EMA is the equivalent of the Food and Drug Administration in the United States. According to the EMA announcement, “A rolling review is one of the regulatory tools that EMA uses to speed up the assessment of a promising medicine or vaccine during a public health emergency. Normally, all data on a medicine’s effectiveness, safety and quality and all required documents must be submitted at the start of the evaluation in a formal application for marketing authorisation. In the case of a rolling review, EMA’s human medicines committee (CHMP) reviews data as they become available from ongoing studies, before a formal application is submitted. Once the CHMP decides that sufficient data are available, the formal application should be submitted by the company. By reviewing the data as they become available, the CHMP can reach its opinion sooner on whether or not the medicine or vaccine should be authorised.”