Cyfendus (anthrax vaccine adsorbed, adjuvanted): what safety margin did regulators accept?

Cyfendus: what safety margin did regulators accept?

anthrax vaccine adsorbed, adjuvanted · B. anthracis PA; TLR9 (CpG 7909 adjuvant)

Safety margin at NOAEL

Not stated in public reviews

Not reported in the public reviews. Reviewers summarise selectively, so this usually means it wasn't discussed publicly, not that it wasn't studied.

NOAEL / key findings

Injection-site necrosis and granulomatous inflammation judged adverse but expected to resolve

“The necrosis and granulomatous inflammation at the injection sites were considered adverse reactions and were expected to resolve over time.”

✓ VerifiedFDA summary basis for approval, p. 16Source ↗

respiratory syncytial virus vaccine, adjuvanted (AS01E) · RSV preF3; TLR4 (AS01E adjuvant)

Rabbit developmental toxicity study: full antigen dose ≈20x the human dose by body weight (3 kg rabbit, 60 kg human)

human papillomavirus bivalent (types 16, 18) vaccine, recombinant, AS04-adjuvanted · HPV 16/18 L1 VLPs; TLR4 (AS04 adjuvant)

No adverse systemic effects at dosages up to more than 50-fold the human dose (body weight basis)

hepatitis B vaccine (rDNA), AS04C-adjuvanted · HBsAg VLPs; TLR4 (AS04C adjuvant)

Safety pharmacology only: no cardiorespiratory effects up to 63-fold the human dose (bodyweight basis); no repeat-dose margin stated

human papillomavirus quadrivalent (types 6, 11, 16, 18) vaccine, recombinant · HPV 6/11/16/18 L1 VLPs

Mouse repeat-dose: ~1450-fold the projected human dose on a body weight basis

human papillomavirus 9-valent vaccine, recombinant · HPV 9-valent L1 VLPs

Rat reproduction studies: up to 240 and 160 times the human dose (mg/kg) without fertility or fetal effects

hepatitis B vaccine (recombinant), adjuvanted · HBsAg; TLR9 (CpG 1018 adjuvant)

Monkey NOAEL 0.5 mg/kg CpG adjuvant, >10-fold the clinical mg/kg dose, for systemic immunostimulation

RTS,S/AS01 malaria vaccine · P. falciparum CSP-HBsAg (RTS,S) VLPs; TLR4 (AS01 adjuvant)

Rabbit study used RTS,S/AS01B with twice the antigen and adjuvant content of Mosquirix; no numeric margin stated

COVID-19 vaccine, recombinant spike protein nanoparticle, Matrix-M-adjuvanted · SARS-CoV-2 spike (nanoparticle)

Rat DART study: dose exceeds the human dose 40-fold on a weight-adjusted basis

hepatitis B vaccine (recombinant), 3-antigen · HBsAg S/pre-S1/pre-S2 VLPs

DART: rats given a dose equivalent to the adult human dose; no numeric multiple stated

zoster vaccine recombinant, AS01B-adjuvanted · VZV glycoprotein E; TLR4 (AS01B adjuvant)

Full human dose given to rabbits, with more doses than clinically; no numeric multiple stated

influenza vaccine, recombinant hemagglutinin · Influenza HA

Not stated in public reviews

hepatitis B vaccine (rDNA) · HBsAg VLPs

Not stated in public reviews