Politics, Policy & Law
Offit, McClellan testimonies aim to bolster trust in COVID-19 vaccine developers, review process
During a House Committee on Energy and Commerce hearing on Wednesday, Paul Offit and Mark McClellan both highlighted multiple “guardrails” designed to protect the COVID-19 vaccine authorization and approval process from political pressure.
Committee members’ questions revolved largely around the ability to trust government agencies and COVID-19 vaccine developers.
Before offering testimony to bolster trust in the vaccine review process, Offit, a member of FDA’s Vaccines and Related Biological Products Advisory Committee and director of the vaccine education center at the Children’s Hospital of Philadelphia, acknowledged the growing mistrust of the agency following emergency use authorizations for hydroxychloroquine and convalescent plasma. “We shouldn’t need this meeting, because we should trust the FDA. We don’t trust the FDA, largely because of what has happened with the administration pushing the FDA to do things it shouldn’t have been doing,” he said.
President Donald Trump has further eroded trust by repeatedly stating at a recent press conference that the White House will make the final decision about criteria for approving vaccines and accusing FDA of attempting to delay approvals for political reasons (see “FDA should distance from White House”; “Trump Contradicts Hahn”).
And in a Tuesday op-ed in The Washington Post, McClellan, who directs the Duke-Margolis Center for Health Policy, and six other former FDA commissioners called out the “deeply troubling ways” the White House has been influencing FDA (see “Former FDA Leaders Call Out White House”).
At the hearing, McClellan said that vaccine developers are aware of FDA’s recommendations in its forthcoming EUA guidance and have designed their trials to reflect the higher standards the agency has said it would apply to COVID-19 vaccines (see “FDA Will Require Data Similar to BLA Standard”).
He added that companies have provided “more transparency than has generally been the case about exactly what their trial plans are” and have written a letter stating they would adhere to FDA’s processes. Moderna Inc. (NASDAQ:MRNA), Pfizer Inc. (NYSE:PFE) and partner BioNTech SE (NASDAQ:BNTX), AstraZeneca plc (LSE:AZN; NYSE:AZN) and Johnson & Johnson (NYSE:JNJ), which have financial support from Operation Warp Speed, have all published the complete protocols for their pivotal trials (see “J&J Could Deliver Late November Readout”; “CEOs pledge rigorous Phase III testing”).
McClellan acknowledged concerns that the accelerated development timelines stimulated by Operation Warp Speed suggests corners had been cut, and pointed out that “FDA is firewalled off from even Warp Speed.” The initiative “is different from the review that’s going on independently by the FDA,” and there is “independent oversight within this very accelerated process to make sure – and that’s FDA’s role – to make sure we’re not cutting corners on the safety and effectiveness evidence,” he said.
Furthermore, Offit and McClellan both emphasized data safety monitoring boards, FDA’s advisory committee, the Centers for Disease Control and Prevention Advisory Committee on Immunization Practices and the integrity of government scientists as shields against premature vaccine authorization.
McClellan added that he trusts the vaccine advisory committee will leave politics out of its recommendations. “They’ll use the FDA’s expert oversight and experience to enable FDA to make an informed decision that reflects all of the science.”
Offitt echoed that decisions would be made based on the science. “I’m on the FDA’s vaccine advisory committee. If you wonder how we operate, I can tell you how we operate. We operate as scientists, clinicians, academicians. That’s what we are. Politics doesn’t enter into that at all,” he said.
Measuring vaccine value
Rep. Morgan Griffith (R-Va.) also raised concerns during the hearing about how vaccine developers are measuring efficacy, citing a Sept. 22 op-ed in The New York Times by Scripps Research’s Eric Topol and University of Maryland’s Peter Doshi criticizing the fact that the primary endpoints for the most advanced COVID-19 vaccines aim to determine, at a minimum, prevention of mild rather than severe disease. They had stated, “To say a vaccine works should mean that most people no longer run the risk of getting seriously sick.”
In response, Offit said, “I think they’re exactly wrong. I think it’s actually much harder to prevent asymptomatic infection or mildly symptomatic infection. If you can prevent that, you’re much more likely to prevent moderate to severe disease.”
Of the four pivotal vaccine studies receiving Warp Speed funding, only J&J’s ENSEMBLE study states that the primary endpoint measures moderate to severe COVID-19. The pharma’s definition for moderate disease requires at least one symptom indicating pneumonia or pulmonary dysfunction; or at least two symptoms associated with mild disease.
Moderna’s study requires similar symptomatology, though it does not explicitly define it as moderate disease, for assessment of the primary endpoint; the other two trials from Pfizer and BioNTech and AstraZeneca only mandate symptomatic COVID-19.
The design of a U.K. Phase III trial of a Novavax Inc. (NASDAQ:NVAX) candidate suggests that company’s opinion is closer to that of Topol and Doshi. The study has prevention of symptomatic COVID-19 and prevention of moderate or severe COVID-19 as co-primary endpoints, though the biotech has not yet disclosed its definition for moderate COVID-19.
Gregory Glenn, president for R&D at Novavax, previously told BioCentury the requirement to demonstrate efficacy in moderate to severe COVID-19 is more stringent, and will enhance confidence that the vaccine produces meaningful protection (see “Novavax COVID-19 Trial”).