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.
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.
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.”