LONDON - The EU has secured a supply of the most advanced COVID-19 vaccine in development, in a deal with Astrazeneca plc for up to 400 million doses of AZD-1222, with deliveries starting by the end of 2020.

The agreement has been signed with the ‘inclusive vaccines alliance’ formed by Germany, France, Italy and the Netherlands, but will also make AZD-1222 available for other countries in Europe.

While the four countries spearheaded this negotiation, on June 12 EU health ministers gave the European Commission a mandate to negotiate advance purchase agreements for up to six different COVID-19 vaccines, for all member states, using a €2.3 billion emergency fund.

“It was very important for us that the European discussion took place for all of Europe – the four countries have done it on behalf of Europe,” said Pascal Soriot, Astrazeneca CEO, making the announcement from his home via Zoom in the middle of Saturday afternoon, June 13.

To date, Astrazeneca has advance purchase agreements for 300 million doses with the U.S.; 100 million for the U.K.; 700 million doses for the Gavi vaccines alliance and the Coalition for Epidemic Preparedness Innovation, for use in low- and middle-income countries; and a manufacturing agreement with the Serum Institute of India for 1 billion doses.

Astrazeneca also is in discussions with other governments, including China, Russia, Brazil and Japan.

Soriot said AZD-1222, which uses an adenovirus to deliver the genetic code for the spike protein that the SARS-CoV-2 virus uses to engage and enter human host cells, will be delivered at cost – of around €2 per dose – during the pandemic.

Supply chains, tech transfer, facilities lined up

There are now independent supply chains in place in Europe, the U.S. and Asia, and technology transfer, validation of facilities and staff training has begun.

On June 11, Cambridge, U.K.-based Astrazeneca said Emergent Biosolutions Inc. of Gaithersburg, MD, will be the U.S. manufacturing partner. AZD-1222 is one of several vaccine candidates being funded by Operation Warp Speed, the U.S. government program to accelerate development and manufacturing. The agreement with Emergent is valued at approximately $87 million.

The advance purchase agreements now in place cover Astrazeneca’s direct costs, but, Soriot said, there is an opportunity cost for the company. “I have hundreds of employees dedicated to working on this vaccine. They are spending time working on the vaccine which is time they should be spending on other products.”

“That’s why it was important to share the risk with governments,” said Soriot, “The cost is not that high on a unit basis [but at] 7 billion times €2, there’s no way a company like ours can carry the cost.”

Of course, everyone loses if AZD-1222 is not effective. Soriot said he “has good hope it will work, from the data we have so far.”

Astrazeneca is still blinded to the results of the phase I/II U.K. trial carried out by scientists at Oxford University who designed the vaccine, but with the U.K. Medicines and Healthcare products Agency having given approval for phase III, Soriot said he “assumes” there is positive efficacy and safety data.

It is expected the results of the phase I/II will be published before the end of this month.

‘Not cutting corners'

The U.K. arm of the phase III trial currently is recruiting 10,000 volunteers, with an emphasis on recruiting health care workers, who are more at risk of exposure to the virus. The U.S. phase III will recruit 30,000 volunteers in July.

There are concerns that with the number of infections falling, it will not be possible to show efficacy in these field trials. Given this, Astrazeneca has launched a study in 5,000 volunteers in Brazil, where infections are still on the rise, and also is working on starting trials in other countries in Latin America, which is now the epicenter of the global pandemic.

While manufacturing commercial supplies in parallel to running the clinical program, Soriot pledged there are no short cuts in terms of safety and efficacy. “By the end of development, 50,000 plus people will have received the vaccine. [The] safety database will be as large as any vaccine ever developed before,” he said.

“We are moving very quickly, but not cutting corners. We are working hand in hand with regulators … talking to them on a daily basis, sharing data. The regulators could not do that for every drug, but this is a priority,” said Soriot.

It will be known by the end of August or early September if AZD-1222 is effective.

“If it works, it will be the first to be rolled out at scale,” said Soriot. “We take this as a very serious responsibility.”

If not, it has been agreed that the AZD-1222 manufacturing capacity will be freed up for other COVID-19 vaccines coming through the pipeline.

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