EU Authorizes AstraZeneca’s COVID-19 Vaccine as Dose Delivery Crisis Deepens

The European Commission granted a conditional marketing authorization on Friday for AstraZeneca’s (AZ) COVID-19 vaccine just hours after an expert panel gave its blessing to the low-cost vaccine that can be shipped and held at normal refrigerator temperatures — as the bloc intensified efforts to secure delivery of initial doses and some EU members questioned the vaccine’s effectiveness for older individuals.

The European Medicines Agency (EMA)’s human medicines committee based its positive recommendation on the vaccine to the commission on four phase 3 trials ― conducted in the UK, Brazil and South Africa ― involving 24,000 participants.

The studies showed an efficacy of nearly 60 percent, with 64 of 5,258 trial participants with COVID-19 infections given the vaccine vs. 154 of 5,210 of trial participants with COVID-19 infections receiving control injections. While each of the four trials provided safety data, only two of them provided actual efficacy numbers. The vaccine works by using a modified adenovirus to target the SARS-CoV-2 spike protein to generate neutralizing antibodies and T-cells.

The EMA recommended administering the two needed doses between four and 12 weeks of each other, with the vaccine indicated for those 18 years of older. Side effects were found to be minimal and EMA officials said AZ would be conducting postmarket studies for at least a year to gather follow-up safety data and determine how long immunity would last.

Germany’s vaccine authority recommended not authorizing the vaccine for people aged 65 and older and other EU member states also questioned whether those over age 65 should be excluded from the recommendation, given limited efficacy data for older adults. But the EMA and scientists at Oxford University, which co-developed the vaccine, said immune responses were similar in older adults and there is no reason to believe the vaccine wouldn’t be safe or effective for this population.

AZ CEO Pascal Soriot promised that more information on elderly populations would be available when data from a now fully enrolled 30,000-participant trial in the U.S. is released this month. The results of the U.S. trial are expected to form the basis of an Emergency Use Authorization submission to the FDA (DID, Dec. 4, 2020).

As UK regulators did when they approved the AZ vaccine in December, the EMA panel excluded phase 3 trial data from a subset of participants who appeared to be better protected after receiving a half dose followed by a full dose (DID, Jan. 4). The regulatory body said the data didn’t allow reliable conclusion to be drawn.

The authorization means that the EU now has three available vaccines, including the highly effective messenger-RNA vaccines from Pfizer/BioNTech and Moderna.

But the good news of the conditional authorization was tempered by an ongoing wrangle between the company and the European Commission about the delivery of doses as scheduled.

AZ took the unusual step of releasing a redacted version of its supply contract, seeking to show that it is only committed to making its “best effort” to supply to the agreed schedule. Commission officials said the company’s shock announcement that it would cut its initial supply to the EU by 60 percent meant that the block would only receive 31 million doses by March. AZ reportedly said it can supply an additional 8 million, but the EU contends that the contract does not allow it to reduce its supply to the EU while fully supplying the UK.

Per its contract, AZ is committed to supplying the bloc with up to 400 million doses on a set schedule, but the two parties have been warring over what delivery guarantees the contract’s “best effort” clause provides.

The commission plans to establish a “transparency and authorization mechanism,” giving it the authority potentially to stop vaccine exports to other countries, like the U.S., until all the European Union contractual agreements have been met. Under the mechanism, set to last through March, drugmakers will be required to notify the commission abouts any “intention to export vaccines produced in the EU.”

The mechanism does exempt vaccine distribution to the World Health Organization (WHO)-backed COVAX initiative, which has secured approximately 2 billion vaccine doses and aims to inoculate 20 percent of each participating nation’s population with deliveries starting this quarter (DID, Jan. 25). — Jason Scott