FDA, CDC recommend J&J vaccine pause while rare clots investigated

Regulatory NewsRegulatory News | 13 April 2021 |  By 

In a joint statement followed by a Tuesday morning press conference, the US Food and Drug Administration (FDA) and Centers for Disease Control and Prevention (CDC) have recommended that administration of the one-dose Johnson & Johnson COVID-19 vaccine be paused.
The recommendation follows reports of six US cases of women between the ages of 18 and 48 years who received the vaccine and then experienced cerebral venous sinus thrombosis (CVST) – a blood clot in a large vessel draining blood near the base of the brain – in combination with low blood platelet counts, or thrombocytopenia.
To date, one patient has died and another is critically ill following vaccination with the Johnson & Johnson vaccine, develop by Janssen, the firm’s vaccines unit. The cases occurred between 6 and 13 days after receiving the Johnson & Johnson human adenovirus vector vaccine. Approximately 7 million doses of the Johnson & Johnson vaccine have been administered in the US.
The CDC’s Advisory Committee on Immunization Practices (ACIP) will meet Wednesday “to further review these cases and assess their potential significance,” according to the joint statement.
In the press conference, CDC’s principal deputy director Anne Schuchat, MD, said that after ACIP’s Wednesday meeting, the CDC is “committed to expeditious review, but that the pause “provides a time for deliberation.” FDA’s acting commissioner Janet Woodcock, MD, put a tighter frame around the expected timeline, saying she expects “a matter of days for the pause.”
The director of FDA’s Center for Biologics Evaluation and Research, Peter Marks, MD, PhD, noted that the pause was recommended in part because of reports from Europe’s EudraVigilance system of a similar pattern of CVST and low platelets after administration of the adenovirus-based COVID-19 vaccine jointly developed by the University of Oxford and AstraZeneca. (RELATED: "Very rare" thrombotic events with AZ vaccine, concludes EMA's PRAC, Regulatory Focus 09 April 2021)
After much deliberation, the safety committee of the European Medicines Agency (EMA) concluded that the AstraZeneca vaccine’s benefits outweigh the risks of the rare complications, but that an association was likely between the vaccine and reported cases of CVST with thrombocytopenia. These data factored into the recommendation for a US pause of the Johnson & Johnson vaccine, affirmed Woodcock. “We are in constant contact with regulators worldwide” as investigations proceed, she said.
“I hesitate to call it a class effect,” said Marks. However, he said, “One, the Astra Zeneca, is a chimpanzee adenoviral vector vaccine; the Janssen is a human adenoviral vector vaccine. So…I can’t make some broad statement yet, but obviously they are from the same general class of vectors.”
Woodcock and Marks confirmed that the working hypothesis of those investigating the vaccines is that an autoimmune activation of platelets triggered by the reaction is at play in the rare cases of CVST with thrombocytopenia. The officials, including Schuchat, agreed that the numbers of those affected are just too low to assess whether host factors, such as a pre-existing condition or the use of oral contraceptives, up the risk of the complication.
They agreed, however, that although blood clots are common in the general population, the very rare risk combination of CVST and low platelets is above background rates among recipients of adenovirus-vectored COVID-19 vaccines. Further, no cases have been reported among the dozens of millions of US recipients of either the Moderna or Pfizer messenger RNA vaccines against COVID-19.
One important consideration in recommending the pause, Marks made clear, is that health care providers need to recognize the potential for the very rare combination of blood clots and thrombocytopenia. If heparin – standard treatment for venous thromboembolism – were administered to an individual with a low platelet count, great harm could result. “The issue here with these types of blood clots is that if one administers the standard treatments that we as doctors have learned to give for blood clots, one can actually cause tremendous harm or the outcome can be fatal,” Marks said, speaking carefully and deliberately.
Still, when asked about the wording of the two agencies in recommending a “pause” rather than a stoppage, Marks emphasized that the announcement “is a recommendation, not a mandate,” made “out of an abundance of caution.” Individuals, in consultation with their health care providers, may still determine that the benefit of the Johnson & Johnson vaccine outweighs the risk, even during the timeframe of the recommended pause, he said.
“I wish that we had more time to get everyone prepared, and that this could go even more smoothly,” said Schuchat, in response to a question about how this recommendation will affect localities in their vaccination efforts.  As the potential for this unusual combination became clear, “it was clear to us that we needed to alert the public we included the pause in addition to the alert so there was time for the healthcare community” to be prepared to treat this very rare condition,” she said.
Marks told attendees at the press conference to look for a statement from Johnson & Johnson regarding immediate plans for ongoing clinical trials of the vaccine.
FDA – CDC joint statement


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