Late Friday, the U.S. Food and Drug Administration (FDA) and the U.S. Centers for Disease Control and Prevention lifted their recommended pause of Johnson & Johnson’s Janssen COVID-19 Vaccine, despite confirming 15 cases of what they termed rare and severe blood clots—three of them fatal. U.S. states have now resumed inoculations of the one-dose vaccine, tapping into the more than 9 million doses available.
“We have concluded that the known and potential benefits of the Janssen COVID-19 Vaccine outweigh its known and potential risks in individuals 18 years of age and older,” Acting FDA Commissioner Janet Woodcock, M.D., said in a statement. “We are confident that this vaccine continues to meet our standards for safety, effectiveness and quality.”
The FDA and CDC on Friday evening followed the advice of the CDC’s Advisory Committee on Immunization Practices (ACIP), which two hours earlier voted 10–4, with one abstention, to recommend lifting of the pause, based on a similar risk-benefit finding.
That finding came despite the FDA and CDC confirming that the number of cases of rare and severe blood clots and accompanying low platelet counts had more than doubled from the six that were disclosed when the agencies called for the pause on April 13.
The FDA and CDC have confirmed 15 cases of thrombosis with thrombocytopenia syndrome (TTS) occurring in patients who had been treated with the J&J vaccine. TTS combines thrombosis involving the cerebral venous sinus thrombosis (CVST) and other sites in the body, including but not limited to the large blood vessels of the abdomen and the veins of the legs, along with thrombocytopenia or low blood platelet counts.
All 15 cases occurred in women between the ages of 18 and 59, with a median age of 37 years. The 15 cases are among 7.89 million recipients of the vaccine nationwide.
“Our vaccine safety systems are working. We identified exceptionally rare events—out of millions of doses of the Janssen COVID-19 administered—and we paused to examine them more carefully,” CDC director Rochelle P. Walensky, MD, MPH said.
Symptoms of TTP “began approximately one to two-weeks following vaccination,” the FDA stated in its Fact Sheet for Recipients and Caregivers. “You should seek medical attention right away if you have any of the following symptoms after receiving Janssen COVID-19 Vaccine: Shortness of breath, chest pain, leg swelling, persistent abdominal pain, severe or persistent headaches or blurred vision, easy bruising or tiny blood spots under the skin beyond the site of the injection.”
One death involved an Oregon woman in her 50s who developed TTP within two weeks of receiving Johnson & Johnson’s Janssen COVID-19 Vaccine, the state’s health agency disclosed on Thursday.
The Oregon Health Authority (OHA) said it was notified of the potential adverse event on Tuesday, two days after the CDC was informed. The CDC has received information about the death through its Vaccine Adverse Event Reporting System (VAERS), the national reporting system used to collect reports of adverse events after vaccination.
CDC: vaccine can prevent 1,435 deaths
An analysis by the CDC found that resumption of the J&J vaccine would prevent 1,435 deaths attributable to COVID-19, and 2,236 admissions to hospital intensive care units.
The agencies said they would continue to investigate the risk of TTS in vaccine patients, adding that “the available data suggest that the chance of TTS occurring is very low.”
However, the FDA also revised its separate “fact sheets” to physicians and to patients and their caregivers, by adding information about the risk of TTS in patients who receive the J&J vaccine.
“Based on currently available evidence, a causal relationship between thrombosis with thrombocytopenia and the Janssen COVID-19 Vaccine is plausible,” the FDA stated in its Janssen COVID-19 Vaccine Fact Sheet for Healthcare Providers Administering Vaccine (Vaccination Providers). “Specific risk factors for thrombosis with thrombocytopenia following the Janssen COVID-19 Vaccine and the level of potential excess risk due to vaccination are under investigation.”
While dosing of the J&J vaccine was paused, the FDA and CDC said, medical and scientific teams examined available data to assess the risk of thrombocytopenia as well as thrombosis involving the CVST and other sites in the body, including but not limited to the large blood vessels of the abdomen and the veins of the legs.
The teams also contacted providers and clinicians “to ensure they were made aware of the potential for these adverse events and could properly manage and recognize these events due to the unique treatment required for these blood clots and low platelets,” the agencies added.
Janssen COVID-19 Vaccine Candidate is an adenovirus vector vaccine based on constructs created and tested by J&J with Beth Israel Deaconess Medical Center (BIDMC), part of Harvard Medical School, using Janssen’s AdVac® and PER.C6® vaccine technology platforms. AdVac can be used with Janssen’s PER.C6® technology to develop recombinant vaccines against infectious diseases.
The J&J vaccine candidate is among 21 “Front Runner” leading candidates among the more than 300 COVID-19 therapeutics under study in GEN’s updated and just-launched “COVID-19 Drug & Vaccine Candidate Tracker.”
“JNJ fine. As expected. Damage done to world confidence in vaccines. Needless,” Robert Nelsen, a co-founder and a managing director of venture capital firm ARCH Venture Partners, tweeted soon after the pause was lifted. “Could have been a bulletin. Let’s move on but not do this again. There will be rare events again, but we are in a pandemic. Bulletins not pauses.”
“Fine unless you get a CVST,” replied Anand C. Patel, MD, MS, vice president, Clinical Development & Leader, Explorations at Pioneering Medicines, the drug discovery entity of life sciences VC firm Flagship Pioneering.
“3/15 died. The idea that discussion of real risks isn’t appropriate doesn’t help vaccine acceptance,” Patel wrote. We have vaccines with fewer AEs [adverse events] as well and plenty of doses. Let people make informed choices.”