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The slides from the Novavax presentation are available as a PDF file from here ( https://www.fda.gov/media/164812/download ). Note a few slides in the video presentation have been updated from the deck you can download. 2/

While the original Novavax formula held up well for multiple variants including BA.1 and BA.5, the company believes the reduced performance from the newer BQ.1.1 and XBB.1 variants is due to mutations in regions that were previously conserved even in BA.2 and BA.5. 3/

Novavax found that antibody levels were lower but similar to those induced by the bivalent mRNA vaccines and those levels were likely associated with continued protection against severe outcomes.

Novavax expects to update its vaccine composition to restore cross-reactivity for future variants. 4/

Independent US government and NIH analysis was performed on Novavax's US/Mexico phase 3 clinical trial to determine correlates of risk and correlates of protection 2 weeks after the second dose over the subsequent 7-59 days ( https://www.nature.com/articles/s41467-022-35768-3 ).

This clinical trial was run later than others so the majority of COVID cases were caused by variants, mostly Alpha but also Beta, Gamma, Epsilon, and Iota. Overall they found efficacy of 90%. 5/

The researchers found that anti-spike IgG antibody response in the Novavax vaccine actually correlated more strongly with protection than neutralizing antibody levels. Although neutralizing antibody responses are important, Novavax knows from other studies that the vaccine induces high levels of IgG antibodies capable of a range of immunological mechanisms. 6/

The anti-spike IgG antibody level correlates were measured to be the following estimate of vaccine efficacy:
95% = 6,934 BAU/ml
88% = 1,000 BAU/ml
65% = 100 BAU/ml

The neutralizing antibody level correlates were measured to be the following estimate of vaccine efficacy:
93% = 1,000 IU50/ml
82% = 100 IU50/ml
76% = 50 IU50/ml

7/

The study also found that correlate results supported that both spike IgG and nAb (neutralizing antibody) performed similarly as correlates as previously found in mRNA vaccine correlate studies allowing for a potential common correlate for both recombinant protein (Novavax) and mRNA (Pfizer/Moderna) COVID-19 vaccines to be used. 8/

Novavax also presented results from their USA adolescent clinical trial (age 12-17) showing high levels of neutralization after receiving a third dose about 10 months after dose 2 for both BA.1 and BA.4/5 variants. 9/

Novavax once again spoke about how IgG and nAb levels were similar between their original vaccine formula, a BA.1 specific booster, and bivalent booster for both BA.1 and BA.5 variants leading to their decision not to release a bivalent version of their vaccine this past fall. 10/

The company presented what everyone has been wondering, how well does the Novavax vaccine hold up against the BQ.1.1 "Cerberus" and XBB.1 "Hippogryph" variants. Since the original formula of Novavax seemed to hold up well for BA.1, BA.2, and BA.5 what about these newer even more immune evasive variants?

Their results compare people with 3 and 4 doses of only Novavax, 3 mRNA monovalent, 4 mRNA monovalent, 3 mRNA monovalent + 1 mRNA bivalent, and 3 mRNA monovalent + 1 Novavax doses. 11/

With all combinations of vaccines the neutralization response was significantly suppressed with BQ.1.1 and even lower responses with XBB.1.

Whether you have only Novavax, only mRNA, a bivalent mRNA, or combination, the neutralization responses for the latest variants while slightly different are all in the same ballpark. 12/

Dr. Wang's testing the neutralization levels for BQ.1.1 resulted in this order:
396 = Novavax x 4
337 = mRNA x 3 + bivalent mRNA x 1
334 = Novavax x 3
261 = mRNA x 4
176 = mRNA x 3 + Novavax x 1
139 = mRNA x 3

Dr. Wang's testing the neutralization levels for XBB.1 resulted in this order:
162 = mRNA x 3 + bivalent mRNA x 1
137 = mRNA x 4
108 = mRNA x 3
82 = Novavax x 4
80 = mRNA x 3 + Novavax x 1
72 = Novavax x 3

13/

Whether people had only Novavax doses (3 or 4) or they decided to get a Novavax dose after 3 RNA, the neutralization levels were almost identical. 14/

Trying to determine why the original Novavax vaccine elicits much lower neutralization with BQ.1.1 and XBB, they used their own monoclonal antibody designs to determine where binding failed. Their images show the Spike protein in blue, the Receptor Binding Domain (RBD) in grey, the epitope the antibody binds to in pink, and their antibody in green/yellow. 15/

With the NVX.425.6 monoclonal, for the original strain, BA.2 and BA.5 they found no mutations in the RBD which provided very good neutralization. BQ.1.1 has a mutation in K444T and XBB has mutations in K445P and G446S and these structural changes result in decreased binding and lower neutralization from Novavax elicited antibodies. 16/

With the NVX.35.13 monoclonal, original strain and BA.2 had no mutations in the RBD where the antibody binds but they found BA.5 and BQ.1.1 had mutations in F486V and XBB had a mutation in F486S that decreased binding and lowered neutralization from Novavax elicited antibodies. 17/

Novavax believes changes to these regions in the virus are the cause of lower neutralization results seen in the clinical studies. The original Novavax vaccine elicited antibodies for certain regions on the virus (epitopes) which had mostly been conserved in later variants such as Delta, BA.1, BA.2, and mostly in BA.5. When those previously conserved regions are altered as with BQ.1.1 and XBB variants, neutralization response decreases. 18/

Their NVX.322.3 monoclonal shows there still are some conserved epitopes that antibodies elicited from the Novavax vaccine can bind to with no mutations in the original strain, BA.2, BA.5, BQ.1.1, and XBB variants. This may help explain why the original Novavax vaccine still provides some neutralization against BQ.1.1 and XBB. 19/

Novavax concludes their presentation pointing out that the breadth of immune response against future-drift variants makes the Novavax technology an appealing choice for future vaccination campaigns. They showed that even their original vaccine formula is showing comparable performance to currently available vaccines including bivalents. 20/

Novavax is prepared to create and deliver recommended monovalent or bivalent vaccines for the fall vaccination season based on guidance from the FDA. They would like the strain recommendation to be provided by the end of Q1 (similar to influenza) to allow 6 months for vaccine manufacture, release and distribution. 21/