Latest cut of data shows AZ vaccine has higher rates of rare thrombosis
Regulators left to tease out why rates higher in lone vaccine
The most recent set of COVID-19 vaccine adverse events in Europe show a higher frequency of several rare types of thromboembolic events in individuals given AstraZeneca’s vaccine compared with others approved in the U.K. and EU.
As an EMA safety committee readies to give an updated recommendation on use of the vaccine, the regulator may be weighing whether the issue is specific to the one vaccine and, if so, why.
An analysis of EudraVigilance adverse event data revealed 82 reports noting disseminated intravascular coagulation (DIC; 16 reports) or cerebral venous sinus thrombosis (CVST; 66 reports) in individuals in the European Economic Area who received Vaxzevria (AZD1222) from University of Oxford and AstraZeneca plc (LSE:AZN; NASDAQ:AZN). As of Monday, 22.4 million doses of the AZ vaccine have been administered in the EEA.
By contrast, EudraVigilance documented one DIC and nine CVST events among 59.8 million administered doses of Comirnaty (BNT162b2) from Pfizer Inc. (NYSE:PFE) and BioNTech SE (NASDAQ:BNTX) and no cases among the 8.9 million doses of COVID-19 Vaccine Moderna from Moderna Inc. (NASDAQ:MRNA) doled out in the EEA.
Similarly, an April 1 update from the U.K.’s MHRA stated that there were 22 cases of CVST plus eight other thrombotic events with co-occurring thrombocytopenia across 18.1 million Vaxzevria doses through March 24, versus no reports of the events for Comirnaty.
As of March 21, about 26.6 million individuals in the U.K. have received their first shot of Comirnaty.
BioCentury’s previous analysis of safety events in the EEA, based on reports through March 13, found similar rates of CVST, deep vein thrombosis and pulmonary embolism across Vaxzevria, Comirnaty and COVID-19 Vaccine Moderna recipients.
In a March 21 EMA safety update on AZ’s adenoviral vector vaccine, the agency said a preliminary assessment by its Pharmacovigilance Risk Assessment Committee (PRAC) found that incidence rates of a subset of thromboembolic events — specific thrombotic and embolic events in combination with low platelet counts including DIC and CVST — with 14 days of vaccination were higher than in the general population. Most of the cases were in women under age 55.
PRAC’s latest assessment specified DIC and CVST but not pulmonary embolism or deep vein thrombosis, and stated that the overall thromboembolism incidence rate in Vaxzevria recipients was “lower than the rate of such events in the general population.”
PRAC’s preliminary conclusion was that “a causal link of DIC and CVST with the vaccine is not proven but cannot be excluded and requires further investigation.”
The committee is expected to provide an updated recommendation on Vaxzevria this week during its April 6-9 plenary meeting.
The guidance may include limiting use of Vaxzevria to older adults, a precaution Canada instituted last week.
MHRA CEO June Raine told BioCentury the U.K. agency’s position on the matter is, “People should continue to get their vaccine when invited to do so.”
She added, “Our thorough and detailed review is ongoing into reports of very rare and specific types of blood clots with low platelets following the COVID-19 Vaccine AstraZeneca. No decision has yet been made on any regulatory action.”
PRAC may also suggest careful monitoring post-immunization for the thromboembolic events occurring in concert with reduced platelet counts, and treating them with anticoagulants. A study, described in a preprint posted March 29, had found that the rare safety events reported in some AZ vaccine recipients resembled heparin-induced thrombocytopenia.
FDA declined to comment on the matter.
If Vaxzevria is determined to occasionally cause DIC or CVST, it would raise questions of whether the issue is specific to the one vaccine and, if so, why.
Compared with mRNA vaccines, adenoviral vectors appear to possess stronger propensities for inducing CD8+ T cell responses. Whether the higher DIC and CVST rates are associated with modality may be revealed as more people receive COVID-19 Vaccine Janssen, an adenoviral vector vaccine from Johnson & Johnson (NYSE:JNJ).
J&J’s vaccine uses human adenovirus serotype 26 whereas Vaxzevria uses a chimpanzee vector.
Other differences between the two adenoviral vector vaccines include the protein sequence of the spike antigen. Vaxzevria uses the wild-type spike sequence whereas J&J’s vaccine contains two amino acid substitutions that stabilize the antigen in its “prefusion” conformation.
Comirnaty and COVID-19 Vaccine Moderna also incorporate the two stabilizing mutations.