Nuvaxovid
COVID-19 vaccine, recombinant spike protein nanoparticle, Matrix-M-adjuvanted · SARS-CoV-2 spike (nanoparticle)Australia: Study 2019nCoV-101 Part 1, started May 2020
Fendrix: what was done before first-in-human, and what came after?
hepatitis B vaccine (rDNA), AS04C-adjuvanted · HBsAg VLPs; TLR4 (AS04C adjuvant)
Before first-in-human
First-in-human: where
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.
Repeat-dose tox before first-in-human
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.
First-in-human starting dose
Not stated in public reviews
Why it's blank
The public FDA and EMA reviews of Fendrix don't say how the first human dose was chosen. That rationale is in the IND, which is confidential, so it is missing for most approved products.
How it's usually set for vaccines outside oncology
Find the highest dose with no adverse effects (NOAEL) in each animal species, convert it to a human equivalent dose, usually by body surface area, pick the most appropriate species, then divide by a safety factor (default 10) to get the maximum recommended starting dose.
“In general, one should consider using a safety factor of at least 10. The MRSD should be obtained by dividing the HED by the safety factor.”
This product's starting point
NOAEL / key findings: No NOAEL stated; minor dose-related immunostimulatory effects with MPL; minor reversible injection-site inflammation in rabbit (EMA assessment report, p. 9)
Longest repeat-dose systemic studies
Longest repeat-dose study and recovery
14-day IV MPL study in Beagle dog; rabbit IM vaccine study duration not stated
“Repeated-dose toxicity studies were presented, up to 7 days in rats and 14 days in Beagle dogs, where MPL was given once daily by the intravenous route, maximising the exposure.”
Pivotal GLP studies
Rabbit IM repeat-dose vaccine study; MPL alone IV daily up to 7 days (rat) and 14 days (Beagle dog)
“Repeated-dose toxicity studies were presented, up to 7 days in rats and 14 days in Beagle dogs, where MPL was given once daily by the intravenous route, maximising the exposure.”
DART package
Species: DART
Rabbit (teratogenicity) and rat (pre- and postnatal development)
“Reproductive toxicity studies including a teratogenicity study in the rabbit and a pre-and postnatal study in the rat showed no evidence of maternal toxicity, teratogenicity or any effect on the in utero development of the F1 offspring.”
Reproductive & developmental
Rabbit teratogenicity and rat pre/postnatal studies: no maternal toxicity, teratogenicity or F1 developmental effects
“Reproductive toxicity studies including a teratogenicity study in the rabbit and a pre-and postnatal study in the rat showed no evidence of maternal toxicity, teratogenicity or any effect on the in utero development of the F1 offspring.”
PPND / ePPND: when
Rat pre- and postnatal study completed before the marketing application
“Reproductive toxicity studies including a teratogenicity study in the rabbit and a pre-and postnatal study in the rat showed no evidence of maternal toxicity, teratogenicity or any effect on the in utero development of the F1 offspring.”
Carcinogenicity
Species: carcinogenicity
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.
Carcinogenicity model
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.
Carcinogenicity timing
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.
Same question, other vaccines
PreHevbrio
hepatitis B vaccine (recombinant), 3-antigen · HBsAg S/pre-S1/pre-S2 VLPsIsrael, Thailand and Singapore: legacy dose-ranging studies, one with a first-in-human part up to 20 µg
Arexvy
respiratory syncytial virus vaccine, adjuvanted (AS01E) · RSV preF3; TLR4 (AS01E adjuvant)Not stated in public reviews
Cervarix
human papillomavirus bivalent (types 16, 18) vaccine, recombinant, AS04-adjuvanted · HPV 16/18 L1 VLPs; TLR4 (AS04 adjuvant)Not stated in public reviews
Cyfendus
anthrax vaccine adsorbed, adjuvanted · B. anthracis PA; TLR9 (CpG 7909 adjuvant)Not stated in public reviews
Flublok
influenza vaccine, recombinant hemagglutinin · Influenza HANot stated in public reviews
Gardasil
human papillomavirus quadrivalent (types 6, 11, 16, 18) vaccine, recombinant · HPV 6/11/16/18 L1 VLPsNot stated in public reviews
Gardasil 9
human papillomavirus 9-valent vaccine, recombinant · HPV 9-valent L1 VLPsNot stated in public reviews
HBVaxPro
hepatitis B vaccine (rDNA) · HBsAg VLPsNot stated in public reviews
Heplisav-B
hepatitis B vaccine (recombinant), adjuvanted · HBsAg; TLR9 (CpG 1018 adjuvant)Not stated in public reviews
Mosquirix
RTS,S/AS01 malaria vaccine · P. falciparum CSP-HBsAg (RTS,S) VLPs; TLR4 (AS01 adjuvant)Not stated in public reviews
Shingrix
zoster vaccine recombinant, AS01B-adjuvanted · VZV glycoprotein E; TLR4 (AS01B adjuvant)Not stated in public reviews