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
Arexvy: what was done before first-in-human, and what came after?
respiratory syncytial virus vaccine, adjuvanted (AS01E) · RSV preF3; TLR4 (AS01E 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
Preliminary results of the GLP rabbit repeat-dose study supported initiation of the first clinical study (pre-IND)
“Section 15 includes a summary of available results from the ongoing pharmacology studies and the preliminary results of the GLP repeat-dose toxicity study conducted in rabbits with the”
First-in-human starting dose
Not stated for first-in-human; final 120 µg RSVPreF3 + 50 µg AS01E dose selected on clinical data
“The final formulation, antigen and adjuvant doses (120 µg RSVPreF3 with 50 µg AS01E) was selected based on clinical data.”
Longest repeat-dose systemic studies
Longest repeat-dose study and recovery
Two GLP rabbit IM studies: injections on Days 1, 15 and 29, then 4-week recovery
“Two GLP-compliant repeated dose toxicity studies (and) were conducted in New Zealand White rabbits (10/sex/group), which received three intramuscular injections (Day 1, Day 15 and Day 29, followed by a 4- week recovery period.)”
Pivotal GLP studies
Two GLP rabbit IM studies of RSVPreF3 alone or with AS01B, three injections two weeks apart, with 4-week recovery
“Two GLP-compliant repeated dose toxicity studies (and) were conducted in New Zealand White rabbits (10/sex/group), which received three intramuscular injections (Day 1, Day 15 and Day 29, followed by a 4- week recovery period.)”
DART package
Species: DART
Rabbit (RSVPreF3 alone; complete RSVPreF3/AS01E product) and rat (RSVPreF3 alone)
“The Applicant has provided two DART studies with RSVPreF3 (without adjuvant): one in rabbit (doses of 120 μg antigen) and one in rat (doses of 48 μg antigen). In addition, the report from a DART study with the complete product (i.e., RSVPreF3/AS01E; full human dose, 120 μg PreF3) in rabbit was provided.”
Reproductive & developmental
Rabbit (RSVPreF3; RSVPreF3/AS01E) and rat (RSVPreF3) DART: no effects on female fertility, embryo-fetal or pre/postnatal development
“In addition, the report from a DART study with the complete product (i.e., RSVPreF3/AS01E; full human dose, 120 μg PreF3) in rabbit was provided. In neither of the studies effects were observed on female fertility, embryo-foetal, pre- and postnatal development.”
PPND / ePPND: when
Rabbit (RSVPreF3 or AS01B) and rat (RSVPreF3) developmental studies with postnatal phase, completed before the marketing application
“Study number 3: A Developmental Toxicity Study (Including Teratogenicity and Postnatal Investigations) of RSVPreF3 or AS01B by Intramuscular Injection in Rabbits. Study number: 20152506. Performing laboratory: . Study initiation date: November 08, 2018 Final report date: September 17, 2019”
Carcinogenicity
Species: carcinogenicity
Not conducted (not required for vaccines)
“The absence of carcinogenicity studies is accepted and not required for vaccines.”
Carcinogenicity model
Not conducted (not required for vaccines)
“The absence of carcinogenicity studies is accepted and not required for vaccines.”
Carcinogenicity timing
Not required for vaccines
“The absence of carcinogenicity studies is accepted and not required for vaccines.”
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
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
Fendrix
hepatitis B vaccine (rDNA), AS04C-adjuvanted · HBsAg VLPs; TLR4 (AS04C 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