US FDA Leaves Pfizer’s Efficacy Data Out Of Under 5 EUA Due To ‘Data Maturity,’ Lack of ‘Confidence’
Executive Summary
Moderna’s ‘more mature’ vaccine efficacy data in children under 6 get agency highlight due to what Peter Marks called a ‘confidence’ difference in the numbers, the but CBER chief also said differences between Moderna’s and Pfizer’s vaccines are ‘subtle’ in this age group.
The US Food and Drug Administration’s authorization materials for Pfizer Inc./BioNTech SE and Moderna, Inc.’s COVID-19 vaccines in the youngest Americans includes one noticeable difference between the two products – while Moderna’s vaccine efficacy data for young children is highlighted, Pfizer’s more premature data is missing.
The difference reflects a higher level of confidence FDA said it has in the available Moderna data.
FDA issued the authorizations for Moderna’s COVID-19 vaccine for children 6 months to 17 years of age and for Pfizer’s COVID-19 vaccine for children 6 months through 4 years on age 17 June, marking the first time COVID-19 vaccines were cleared for children under 5 in the US.
Moderna’s application included a greater wealth of data that is reflected in agency’s communications. (Also see "COVID Vaccines For 5 and Under: Pfizer Pivot To 3 Shots Leaves Meager Data Package Compared To Moderna" - Pink Sheet, 13 Jun, 2022.)
FDA’s press release on the new emergency use authorizations includes vaccine effectiveness data seen in Moderna’s trial for children 6 through 23 months and 2 through 5 years of age. The health care provider fact sheet for Moderna’s vaccine in this age group also includes the efficacy data.
Pfizer’s more preliminary efficacy figure is notably absent in both the release and Pfizer’s health care provider fact sheet.
“The Moderna data on effectiveness was more mature than the Pfizer three-dose data, we were able to feel confident in the numbers that were given,” Peter Marks, director of FDA’s Center for Biologics Evaluation and Research said on a 17 June press call.
Marks said FDA is “comfortable” with the effectiveness and safety of both of the vaccines given both met their primary immunobridging objectives – efficacy was a secondary endpoint – but said FDA “will have to wait a little bit longer for Pfizer to have more mature effectiveness data to have the kind of confidence that we’d like to put out numbers.”
FDA’s vaccines advisory committee member Amanda Cohn, the Centers for Disease Control and Prevention’s Chief Medical Officer for the National Center for Immunizations and Respiratory Diseases, had specifically cautioned the agency against using Pfizer’s more preliminary efficacy estimate out of concern that people would wrongly compare the two sponsors products to each other and think Pfizer’s was better. (Also see "Moderna, Pfizer Nab Unanimous Votes For Pediatric COVID Vaccines But Advisors Hint At Moderna Dosing Advantage" - Pink Sheet, 15 Jun, 2022.)
FDA Declines To Play Favorites, Says Differences Are ‘Subtle’
Despite the differences in available data and the practical differences in a two-shot (Moderna) versus three-shot (Pfizer) primary vaccine series, both Marks and FDA Commissioner Robert Califf declined to offer a preference for one product over the other.
“The differences between the two are so much less than the fundamental benefit to risk balance,” Califf said, adding that he’d recommend his grandchildren in this age range get the first shot available.
The two vaccines have “their own nuanced benefits and risks compared to each other. … It may be that the Moderna vaccine brings an immune response slightly more rapidly. On the other hand, the three-dose Pfizer regiment may also bring a greater immune response after the third dose, and there are some subtle differences in the safety profile. But again, these are relatively subtle,” said Marks, who like Califf recommended getting whichever product is available.
Simultaneous Authorization Did Not ‘Delay’ Moderna
At the press briefing, Marks also addressed continued concerns that FDA held up its review and authorization of Moderna’s vaccine in younger children so it could clear it at the same time as Pfizer’s shot for this age group.
Marks pushed back on the idea that FDA “delayed” Moderna’s clearance and said one reason the timing converged was because FDA was dealing with a larger application for Moderna. The sponsor’s vaccine for the older pediatric populations had been held up for about a year due to concerns the vaccine might come with a heightened risk of adverse heart events compared to Pfizer’s vaccine. (Also see "Moderna COVID Vaccine’s Myocarditis Risk Has Improved With Time, US FDA Says" - Pink Sheet, 13 Jun, 2022.)
“We had a lot of material to work through for the Moderna submission that needed to be analyzed. There was an entire submission from six months through 17 years of age. It was very important to get that correct.”
FDA officials had previously indicated they could approve a vaccine for a younger age group ahead of an older one. However, when asked whether FDA could have broken out the data Moderna had on children under 6 and focused on that part of the application first to speed up the authorization in the age range with complete unmet need, since children five and older already had access to Pfizer’s vaccine, Marks suggested that could have been problematic.
“Could you have tried to break things out differently? I guess we could have tried a variety of different things. But at the end of the day, what we did made the most sense because there are issues for approving a vaccine for a very young population and then having a doughnut hole, where you do not have an approval, that could have created a whole other set of issues,” Marks said.
Marks also argued that the convergence of the authorizations has it benefits as it “actually gives people choice and gives those who want to get into the nuance options.”
Less Pediatric Lag For Updated Vaccines
The agency expects parents will not have to experience the same time lag in getting babies, toddlers and preschoolers access to updated COVID-19 vaccines that has occurred with the first generation of shots.
“The most important thing as we move forward to know, is that as we move into the younger age range, as with boosters, we won’t have to do the same kind of waiting, because we now have the immunobridging we need. We understand what doses are correct for these populations. And so much as the same way as we may change the strains in older individuals we will be able to change strains in younger individuals. And I do not anticipate any substantial delays here if we decide that younger children need an updated strain.”
FDA’s current guidance on updating vaccines to address emerging SARS-CoV-2 variants indicates that “ideally the modified vaccine would be evaluated in subjects spanning the age range for the authorized use of the prototype vaccine,” but says that in certain situations if a more limited age range is studied “it may be reasonable to extrapolate the data to other age groups for which the prototype is authorized or approved.”
The agency will convene a second meeting of its Vaccines and Related Biologicals Products Advisory Committee on 28 June to discuss whether and how the SARS-CoV-2 strain composition of COVID-19 vaccines should be modified. (Also see "COVID Vaccines: US FDA Should Play More Activist Role In Development Of Modified Formulations" - Pink Sheet, 7 Apr, 2022.)