Journavx
suzetrigine
Species
MonkeyRat
Longest study
13 wk
Genotox
Conducted Conducted
Carcinogenicity
Not conducted Not conducted
Repro
Conducted Conducted
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
Rat and cynomolgus monkey
“The following studies were submitted: primary and secondary pharmacology, safety pharmacology in the monkey in addition to in vitro human ether-à-go-go-related gene (hERG) assays; absorption, distribution, metabolism, excretion (ADME) and pharmacokinetic (PK) studies; repeat-dose toxicology studies in the rat and monkey for durations of 28 days and 13 weeks”
Why that species
Monkey: NaV1.8 potency and metabolic profile similar to human
“Based on similarities in potency against NaV1.8 and metabolic profile between monkeys and humans, monkeys were considered an appropriate species for use in the pivotal nonclinical safety studies.”
Surrogate molecule
No surrogate; the clinical compound was tested
“In a 13-week monkey study, animals were treated with SUZ at 0, 20, 50, and 150 mg/kg via oral gavage.”
Study lengthopen answer page →
Longest pivotal study
13 (13-week rat and monkey)
“repeat-dose toxicology studies in the rat and monkey for durations of 28 days and 13 weeks”
Pivotal GLP studies
91-day repeat-dose rat and monkey studies
“In addition, the safety of SUZ and impurities/degradants in the drug substance and drug product was evaluated in 91-day repeat-dose toxicity studies in rats and monkeys.”
Route in tox
Oral (gavage)
“In a 13-week monkey study, animals were treated with SUZ at 0, 20, 50, and 150 mg/kg via oral gavage.”
Skipped studiesopen answer page →
Genotoxicity
Negative in Ames, in vitro TK6 micronucleus and in vivo rat bone marrow micronucleus assays
“Suzetrigine was not mutagenic in the bacterial reverse mutation assay (Ames test), or clastogenic in the in vitro micronucleus assay with a human TK6 lymphoblastoid cell line, or in the in vivo rat bone marrow micronucleus assay.”
Carcinogenicity
Not completed (long-term studies not done for acute-use approval)
“Long-term animal studies have not been completed to evaluate the carcinogenic potential of suzetrigine.”
Reproductive & developmental
Rat fertility: no male effects up to 1000 mg/kg; increased preimplantation loss in females at 15 mg/kg
“SUZ doses up to 1000 mg/kg did not affect male reproductive performance when administered at least 28 days before mating and throughout mating. In a female fertility study in rats, increased preimplantation loss was observed at oral SUZ doses of 15 mg/kg when administered prior to mating and through gestation day (GD) 7.”
Safety pharmacology
No effect on hERG (IC50 >10 µM) for suzetrigine and its M6 metabolite
“SUZ and M6-SUZ were evaluated in good laboratory practice (GLP) in vitro human ether-à-go-go-related gene (hERG) assays, and they had no effect on hERG channel activity (IC50 greater than 10µM).”
First doseopen answer page →
First-in-human starting dose
Not stated in public reviews
Why it's blank
The public FDA and EMA reviews of Journavx 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 small molecules 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: 91-day rat (females): ovarian cysts, fewer corpora lutea, pituitary and mammary hyperplasia (FDA integrated review, p. 66)
NOAEL / key findings
91-day rat (females): ovarian cysts, fewer corpora lutea, pituitary and mammary hyperplasia
“In the 91-day rat study, oral administration of SUZ to female rats for 91 days resulted in ovarian cyst formation, decreased number of corpora lutea, pituitary gland hyperplasia, and mammary hyperplasia/dilatation.”
Risksopen answer page →
Immune & cytokine safety
Not a skin sensitizer in the mouse local lymph node assay
“SUZ was not a skin sensitizer in a local lymph node assay in the mouse.”
Biodistribution & persistence
Reversible melanin binding: rat uveal tract, pigmented skin and meninges peaked at 1-4 h, undetectable by 72 h
“Radioactivity concentrations in melanin-containing tissues in rats (i.e., the uveal tract, pigmented skin, and meninges) peaked between 1 and 4 hours postdose then declined to undetectable levels by 72 hours postdose.”
Modality-specific risk
Female reproductive toxicity, fertility and developmental effects
“General toxicity studies and reproductive toxicity studies performed in rats suggested SUZ may pose risks with respect to adverse effects on female reproductive tissues, fertility, pregnancy, and development.”