Astra’s Covid-19 vaccine woes deepen

Denmark’s suspension of AZD1222 following blood clots heaps even more pressure on Astra’s US study.

Astrazeneca’s PR battle with its Covid-19 vaccine is intensifying. AZD1222 had already faced questions about its efficacy, and now safety is under the spotlight – with the latest scare coming today from Denmark, which has suspended use of the jab as concerns about blood clots mount.

For countries contending with vaccine hesitancy this will be a blow. Even if AZD1222 is exonerated, reports like these will only make those who already have doubts even more reluctant to get a vaccine. For Astra specifically, the latest news makes the readout of its US study this quarter, already an eagerly awaited event, even more important.

Astra shares sank 2% this morning, although it should be stressed that no link has been proven between AZD1222 and thrombotic events.

Still, this has not stopped Denmark pausing use of the vaccine while it investigates blood clots seen in people who had received the Astra vaccine, including a fatality in the country, “based on a precautionary principle”.

Reports have since emerged of Iceland and Norway also suspending use of AZD1222.

Austrian cases

This follows an investigation into a batch of AZD1222 after two serious cases of thombosis, one fatal, in Austria. The EMA said yesterday that its preliminary review had suggested no specific issue with this batch – number ABV5300 – and no indication that the vaccine had caused these cases. Batch ABV5300 was shipped to 17 European countries, including Denmark.

The EMA added that, as of March 9, there had been 22 thromboembolic events among the three million people vaccinated with AZD1222, which it said was no higher than the rate seen in the general population.

This could prove reassuring, along with pooled data from Astra’s pivotal trials outside the US, which found no thrombosis signal with AZD1222.

But thromboembolic events were flagged in the FDA’s recent review of Johnson & Johnson’s Covid-19 jab JNJ-78436735, which like AZD1222 uses an adenoviral vector. In J&J’s pivotal trial there were 15 such events in the vaccine cohort and 10 in the placebo arm; this included a case in the vaccine group that led to the trial being briefly halted, but was later deemed unrelated to the shot.

The agency stressed that there were not enough data to determine a causal relationship between these events and JNJ-78436735; today, the EMA recommended approval of the J&J vaccine, so the EU regulator cannot be concerned, either.

FDA reviews of Pfizer/Biontech’s Comirnaty and Moderna’s mRNA-1273 did not find any imbalances in thrombotic events.

Astra, which told Evaluate Vantage that patient safety was its “highest priority”, will now have to wait for the results of Denmark’s investigation. But the big question is whether an all-clear would restore confidence in a vaccine already damaged by questions about efficacy in over-65s, which led to restrictions in some EU countries and might have contributed to low uptake in Europe.  

Astra has a chance to redeem AZD1222 with its US study, which is due to read out by the end of the month. With safety as well as efficacy now under the spotlight, the stakes for this trial could not be higher.

Via https://www.evaluate.com/node/16708/amp