Thinking the unthinkable on Covid vaccine approvals

With the EU regulator already reviewing two coronavirus vaccines, could it beat the US FDA to the punch?

Policy and regulation

The Covid-19 pandemic has opened up another regulatory divergence between the US FDA and its opposite number in the EU. While in the US the possible approval of a Covid-19 vaccine takes on increasingly political dimensions, the European Medicines Agency has already quietly begun rolling reviews of two vaccines.

Not only that, but one of these is Astrazeneca’s AZD1222, the project whose clinical trials had been halted over an unexplained illness. This might be taken as a signal that the EU regulator is more favourably disposed towards a quick green light, though surely it is a step too far to suggest that the first vaccine might be approved in the EU before the US.

Still, it is worth asking the question. Already the EMA has shown itself willing to move quickly during the pandemic by using a rolling review process; this is not equivalent to the commonly used US rolling submission, but is a special regulatory tool used to speed assessment during a public health emergency.

Gilead’s Covid-19 antiviral Veklury, for instance, received conditional EU approval on 3 July, 65 days after the start of a rolling review. In the US the drug got emergency use authorisation on 1 May, just 23 days after a rolling BLA was initiated, and over three months before this rolling process was completed.

Who’s fastest?

Of course, each filing has to be assessed on its merits, and for now the FDA looks to have moved faster than the EMA. However, no Covid-19 vaccine makers have started a US regulatory process yet.

The EU regulator is already assessing two vaccines, yesterday saying Biontech/Pfizer’s BNT162b2 was under rolling review. This comprises only the first batch of preclinical data, and no conclusion can be reached on safety or efficacy, the EMA cautioned.

A week ago the agency had put in motion the first such rolling review, pertaining to preclinical studies of AZD1222. Clinical trials of AZD1222 had been halted on September 9 over a subject’s unexplained illness; dosing at UK sites resumed shortly afterwards.

Astra made no formal comment on the rolling review process, but Biontech did. “Formal submission could be finalised following the rolling review, pending demonstration of vaccine efficacy and safety and confirmation ... that the submitted data are adequate,” the German group stated yesterday.

Some will read in this a potentially looser stance versus the US. The FDA has for some time been communicating to companies that it wants to see a median of at least two months' safety observations on trial participants as part of any emergency use application.

This issue has taken on huge importance, with President Donald Trump clearly fearing that it would preclude a vaccine approval before the November 3 US election. The FDA reiterated this stance yesterday in an appendix to an upcoming vaccines advisory panel, drawing instant ire from President Trump.

At last month’s FT Pharma and Biotech Summit Stephane Bancel, chief executive of Moderna, which is developing mRNA-1273, denied any political interference, saying nobody had “asked us to go faster or to go slower”.

But he said manufacturing constraints meant a vaccine was unlikely to be made available for weeks after a potential emergency use authorisation. The FDA is requesting extensive manufacturing information at least a month before submission of an emergency application.

This, together with the requirement for an adcom for each vaccine, shows the FDA stamping its authority, and combined with a review time of several weeks makes a pre-election approval look like a pipe dream. Emergency use approval “could take longer than many investors are expecting”, Leerink analyst wrote today.

It is not only investors who might have to rethink the timelines, in the US and EU alike.

Timelines for generation of data necessary for formal approval of Operation Warp Speed Covid-19 vaccines. Numbers refer to expected events. Source: JHU-UW Symposium & Leerink.

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