Pfizer to apply for COVID-19 vaccine EUA after mid-November safety data milestone

Pfizer and BioNTech’s earlier timeline for their mRNA vaccine candidate had suggested the companies would seek regulatory review ‘as early as October 2020’. However, with the FDA now requiring two months of safety data – as per its COVID-19 vaccine guidance published earlier this month – Pfizer's revised timeline puts the availability of this information into November at the earliest.

Pfizer's timeline is now as follows: It ‘may know’ whether or not the vaccine candidate is effective by the end of this month. Safety data is expected in the third week of November. Pfizer will apply for an EUA ‘soon after’ this safety data is available.

Bourla: ‘There is a great deal of confusion regarding exactly what it will take for our vaccine's approval’

Pfizer chairman and CEO Albert Bourla has published an open letter [dated Friday 16 October] outlining the company’s COVID-19 timeline, stating that it is essential for the public to understand its estimated timelines to ensure trust and clear up ‘a great deal of confusion’.

He highlights there are three key areas the COVID-19 vaccine must demonstrate success in if it is to apply for authorization from the FDA.

Firstly, the vaccine must be proven effective (meaning it can help prevent COVID-19 disease in at least a majority of vaccinated patients). Secondly, must also be proven safe – requiring robust safety data from thousands of patients. Finally, Pfizer must show the vaccine can be consistently manufactured at the highest quality standards.

Part 1: Prove the vaccine is effective

Bourla reiterates that Pfizer is ‘operating at the speed of science’.

“This means we may know whether or not our vaccine is effective by the end of October,” he said. “To do so, we must accumulate a certain number of COVID-19 cases in our trial to compare the effectiveness of the vaccine in vaccinated individuals to those who received a placebo. Since we must wait for a certain number of cases to occur, this data may come earlier or later based on changes in the infection rates.

“As Pfizer is blinded to who received the vaccine versus the placebo, a committee of independent scientists will review the complete data and they will inform us if the vaccine is effective or not based on predetermined criteria at key interim analysis points throughout the trial.

“Pfizer will continue running the trial through its final analysis point even if it is declared effective at an earlier stage. In the spirit of candor, we will share any conclusive readout (positive or negative) with the public as soon as practical, usually a few days after the independent scientists notify us.”

Part 2: Prove the vaccine is safe

The safety data will be the set of data that takes the longest for Pfizer to gather: and thus it is this part that will determine when it can submit a request for EUA.

It is also the part of vaccine development with the most attention: with it being crucial for vaccine developers and regulators to assure the public a vaccine is safe if it is to receive large scale uptake.

The FDA’s guidance – released earlier this month - says data from Phase 3 studies should include a median follow-up duration of at least two months after completion of the full vaccination regimen, to help provide adequate information to assess a vaccine’s benefit-risk profile (particularly with regards to any adverse effects, and to assess a longer term protective effect).

“Our internal standards for vaccine safety and those required by regulators are set high,” says Bourla. “In the instance of Emergency Use Authorization in the US for a potential COVID-19 vaccine, FDA is requiring that companies provide two months of safety data on half of the trial participants following the final dose of the vaccine.

“Based on our current trial enrollment and dosing pace, we estimate we will reach this milestone in the third week of November. Safety is, and will remain, our number one priority, and we will continue monitoring and reporting safety data for all trial participants for two years.”

Pfizer's Phase 2/3 clinical trial has enrolled 37,864 participants and 31,062 participants have received their second vaccination (figures published October 12).

Part 3: Show the vaccine can be consistently manufactured

Like others in the vaccine race, Pfizer has been building up vaccine manufacturing capacity and capabilities with partnerships and agreements over the last six months. Pfizer’s readiness to manufacture a vaccine at scale is ahead of other elements, says Bourla.

“Pfizer has been investing at risk since the early days of the pandemic to perfect our manufacturing processes and rapidly build up capacity. We expect to have our manufacturing data ready for submission before the safety milestone is reached,” he said.

Pfizer’s earlier timeline – working on the basis of seeking regulatory approval in October – had suggested producing up to 100 million doses by the end of 2020 and around 1.3 billion doses by the end of 2021. Bourla’s update does not address the impact of the new timeline on production.