COVID-19 Vaccine Regulatory Strategy Evolving With The Pandemic
Executive Summary
AstraZeneca and Novavax have not filed EUAs for their vaccines, and they never might. The pathway remains viable in the short-term, but as BLAs are approved and supplies are no longer short, the window may close.
Reported decisions by AstraZeneca PLC and Novavax, Inc. to alter development and launch strategies for their coronavirus vaccines may not necessarily affect the US campaign against the virus, but could upset global efforts, as well as the US place in them.
With US vaccine supply now outpacing demand, the immediate domestic need for another product is waning. But the impact of US plans to provide vaccine to other countries may wane as well without US Food and Drug Administration sign-off of additional products.
AstraZeneca now is considering skipping the emergency use authorization process and working toward the more labor-intensive and time-consuming full biologics license application, according to the Wall Street Journal. Novavax maintains its commitment to obtain an EUA, but now is not expected to submit the application until June at the earliest, the Washington Post reported.
The US is expected to receive ample supplies of both products once they are available and could immediately send them to other nations where needs are greater. Novavax signed a deal with Operation Warp Speed in 2020 to supply 100 million doses to the US. (Also see "Novavax Plays Down EU COVID Vaccine Contract Delay" - Scrip, 26 Mar, 2021.)
AstraZeneca has agreed to provide 300 million doses to the US government, some of which has already been delivered even though it cannot be used domestically. (Also see "US Is Holding On To Its Supply Of AstraZeneca COVID-19 Vaccine" - Pink Sheet, 12 Mar, 2021.)
But US vaccine diplomacy efforts likely will remain in an awkward position while both companies complete their regulatory filings. The AstraZeneca and Novavax decisions will extend the time before the FDA can assess the applications and potentially make the products available. Globally, the lack of US approval could hinder sales, especially in countries that view FDA approval as a suitable for market availability.
Even if neither product is needed domestically, offering other nations only the products that have not been authorized, while keeping supplies of those with the FDA’s blessing, may not present the look President Biden is seeking for his plans to position the US as a global COVID-19 vaccine supplier.
FDA quality checks of 10 million AstraZeneca vaccine doses remain ongoing to determine whether they can be shared with other countries, the White House said 10 May. Ultimately the US is hoping to release 60 million doses for use around the world. The vaccine was made at the problematic Emergent BioSolutions, Inc. plant in Baltimore, where contamination was discovered. (Also see "Of Patents And Production: Industry-White House Row Over Vaccine Exports Highlights Policy Divide" - Pink Sheet, 26 Apr, 2021.)
AZ Again Says FDA Submission Progressing
AstraZeneca did not confirm the reports of its BLA strategy, stating that it “continues to progress our FDA submission” for the vaccine. The company also noted the size of the pending application, including the extensive clinical trial dataset that has already been developed.
“It is important to note the substantial size of the file,” the company said. “In addition to the US trial data, the filing will also include analyses and pharmacovigilance from all studies to date, in addition to real-world evidence data.”
AstraZeneca’s delay could be a result of lingering questions about the results of its clinical trial, as well as the appearance of cerebral venous sinus thrombosis (CVST) with thrombocytopenia, a rare blood clot that emerged with a similar product from Janssen Biotech Inc.. The FDA recommended holding use of the Janssen product for several days while the events were investigated, but concluded administration could continue. (Also see "AstraZeneca’s COVID Vaccine US Filing Is Delayed – Really Delayed. Here Are Two Theories Why" - Pink Sheet, 21 Apr, 2021.)
Novavax did not respond to questions about the timing of its EUA filing.
The company released a statement 10 May announcing a protocol amendment to its phase III PREVENT-19 trial explaining that “because of increasing availability of emergency use COVID-19 vaccines and public health recommendations for their use, a blinded crossover was initiated in April.” The final analysis for the trial now “will be conducted on events accrued prior to participants receiving crossover vaccine.” An interim analysis had been planned after accrual of 72 events and a final analysis after 144 events, according to the statement. Final data is expected in the second quarter.
Several vaccine sponsors were forced to implement crossover designs in order to limit trial drop-outs once the FDA began issuing EUAs. (Also see "Trial Dropouts Illustrate Worries For J&J, Other Later Entrants To COVID Vaccine Space" - Pink Sheet, 24 Feb, 2021.)
Novavax was predicted to receive its EUA this month or potentially in June if the FDA wanted results of a larger trial conducted in the US and Mexico in the submission. (Also see "Novavax Sets Out Vaccine Strategy For New COVID-19 Variants" - Scrip, 2 Mar, 2021.)
EUA Pathway May Be Affected By US Supply
The decision by Pfizer Inc. and BioNTech SE to begin their rolling submission for full licensure of their COVID-19 vaccine may not be influencing vaccine regulatory strategy yet.
Norman Baylor, a former head of the FDA Center for Biologics Evaluation and Research’s Office of Vaccine Research and Review and now president and CEO of Biologics Consulting, told the Pink Sheet that supply dynamics likely will determine when the EUA pathway falls out of favor.
Baylor said with the vaccine still not available to everyone in the US, even with sinking demand, more products can use the pathway.
“The first BLA approval will not include children below the age of 16, so this is a gap,” he said. “Bottom line, EUA is still a pathway for authorizing vaccines against COVID-19, but the window will be closing as these vaccines are licensed by the FDA.”
The FDA also said that vaccine licensure does not preclude other EUAs from being granted. If supply is limited or licensure is only in a small population, the agency still could consider the product not adequate to address the public health emergency, as outlined in federal law.
Pfizer and BioNTech are providing the FDA with updated manufacturing and clinical data for the BLA, which is expected to be completed in the coming weeks and warrant a priority review. (Also see "Keeping Track: First COVID Vaccine BLA Kicks Off; Oncology Submissions From Hutchmed, Takeda And Shorla" - Pink Sheet, 7 May, 2021.) The companies also received FDA approval on 10 May to expand the indication to children age 12 to 15. (See sidebar.)
VRBPAC To Consider COVID-19 Vaccine Pediatric Development
In addition, the FDA’s Vaccines and Related Biological Products Advisory Committee will discuss further expansion of COVID-19 vaccine use in children during a 10 June virtual meeting.
FDA officials are expected to provide an update on their approach to vaccine EUAs for children age 12 to 17, as well as discuss the path for extending the indication to children younger than 12.
No specific products will be discussed, the agency said in a press release announcing the meeting. As with previous COVID-19 VRBPAC meetings, the agency plans to livestream the event on YouTube and other platforms.
Sponsors are hoping younger adolescents will be able to be vaccinated in time for the beginning of the 2021-2022 school year. (Also see "Adolescent Recruitment For COVID-19 Vaccine Trials Is Worry For Operation Warp Speed" - Pink Sheet, 12 Jan, 2021.)