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Precedia/Protein and VLP vaccines/Cyfendus/Flexibility

Cyfendus: what flexibility did regulators accept, and why?

anthrax vaccine adsorbed, adjuvanted · B. anthracis PA; TLR9 (CpG 7909 adjuvant)
Check my plan vs. these
Flexibility accepted
Efficacy modelAccepted
Effectiveness established from animal post-exposure survival studies under the Animal Rule instead of human efficacy trials
Why: Rapidly progressing, fatal inhalational anthrax makes clinical efficacy trials not feasible or ethical; Animal Rule applies · Within the guideline · Serious disease
“Because of the rapid progression and fatal nature of inhalational anthrax, clinical trials to demonstrate effectiveness of a PEP anthrax vaccine are not feasible or ethical. Therefore, animal post-exposure survival data were used as the basis for demonstration of effectiveness of CYFENDUS for the proposed indication, under the Animal Rule”
✓ VerifiedFDA summary basis for approval, p. 4Source ↗
“No deficiencies were identified with the nonclinical animal studies”
✓ VerifiedFDA summary basis for approval, p. 19Source ↗

Same question, other vaccines

Arexvy

respiratory syncytial virus vaccine, adjuvanted (AS01E) · RSV preF3; TLR4 (AS01E adjuvant)
Toxicity studies used AS01B adjuvant (double immunoenhancer dose) instead of the clinical AS01E formulation

Cervarix

human papillomavirus bivalent (types 16, 18) vaccine, recombinant, AS04-adjuvanted · HPV 16/18 L1 VLPs; TLR4 (AS04 adjuvant)
No genotoxicity or carcinogenicity studies with the vaccine (MPL adjuvant genotoxicity tested only)

Fendrix

hepatitis B vaccine (rDNA), AS04C-adjuvanted · HBsAg VLPs; TLR4 (AS04C adjuvant)
No distribution or excretion data for the final vaccine or AS04C adjuvant

Flublok

influenza vaccine, recombinant hemagglutinin · Influenza HA
No nonclinical toxicity or pharmacology studies with the quadrivalent vaccine; package bridged from trivalent RIV3

Gardasil

human papillomavirus quadrivalent (types 6, 11, 16, 18) vaccine, recombinant · HPV 6/11/16/18 L1 VLPs
No dedicated safety pharmacology studies; physical signs monitored within toxicity studies

Gardasil 9

human papillomavirus 9-valent vaccine, recombinant · HPV 9-valent L1 VLPs
No safety pharmacology study

HBVaxPro

hepatitis B vaccine (rDNA) · HBsAg VLPs
No dedicated nonclinical studies with HBVaxPro; data extrapolated from HEXAVAC, PROCOMVAX and the thiomersal-containing vaccine

Heplisav-B

hepatitis B vaccine (recombinant), adjuvanted · HBsAg; TLR9 (CpG 1018 adjuvant)
Adjuvant-alone 8-week repeat-dose study designs not representative of the clinical dose regimen

Mosquirix

RTS,S/AS01 malaria vaccine · P. falciparum CSP-HBsAg (RTS,S) VLPs; TLR4 (AS01 adjuvant)
No reproductive and developmental toxicity studies

Nuvaxovid

COVID-19 vaccine, recombinant spike protein nanoparticle, Matrix-M-adjuvanted · SARS-CoV-2 spike (nanoparticle)
Rat DART used Matrix-M1 below the absolute human dose (maximum volume of clinical formulation)

PreHevbrio

hepatitis B vaccine (recombinant), 3-antigen · HBsAg S/pre-S1/pre-S2 VLPs
Pivotal repeat-dose toxicity study in rats not GLP-compliant

Shingrix

zoster vaccine recombinant, AS01B-adjuvanted · VZV glycoprotein E; TLR4 (AS01B adjuvant)
Vaccine DART only in rats at 40% of the human dose; no full-human-dose rabbit study

Summary across all 13 vaccines →