Rystiggo
rozanolixizumab
Species
Monkey
Longest study
26 wk
Genotox
Not conducted Not conducted
Carcinogenicity
Not conducted Not conducted
Repro
Conducted Conducted
First dose
Not conducted Not stated publicly
Speciesopen answer page →
Species
Cynomolgus monkey only
“The repeat dose studies were primarily performed in cynomolgus monkey, as the NHP was found to be the only pharmacological relevant species.”
Why that species
Much weaker (nanomolar) affinity for mouse and rat FcRn and no binding to rabbit FcRn
“Affinity (KDs) for rozanolixizumab for mouse and rat FcRn was much weaker (nanomolar range) and binding to rabbit FcRn was not observed at all.”
Surrogate molecule
No surrogate in toxicology; the clinical antibody was tested in cynomolgus monkeys (mouse surrogate 4470 used in pharmacology only)
“The ability of a mouse surrogate (4470) of rozanolixizumab to increase clearance of IgG was evaluated in a mouse disease model of immune thrombocytopenia (ITP).”
Study lengthopen answer page →
Longest pivotal study
26 weeks
“General toxicity studies of 4-, 13- and 26-weeks’ duration were conducted in cynomolgus monkey administered up to 150 mg/kg UCB7665 by SC injection every 3 days.”
Pivotal GLP studies
Cynomolgus monkey 4-, 13- and 26-week studies, up to 150 mg/kg SC every 3 days; monkey ePPND
“General toxicity studies of 4-, 13- and 26-weeks’ duration were conducted in cynomolgus monkey administered up to 150 mg/kg UCB7665 by SC injection every 3 days.”
Route in tox
Subcutaneous and intravenous
“This included GLP-compliant general toxicology studies of up to 26- weeks duration where animals received IV or SC doses of up to 150 mg/kg rozanolixizumab every three days”
Skipped studiesopen answer page →
Genotoxicity
Not conducted
“No genetic toxicology studies were conducted.”
Carcinogenicity
Not conducted; weight-of-evidence assessment judged studies unnecessary
“Based on a weight of evidence assessment, conduct of carcinogenicity studies were deemed not necessary for UCB7665.”
Reproductive & developmental
Monkey ePPND (0, 50, 150 mg/kg SC every 3 days, GD 20 to parturition): embryonic losses in 3 of 19 females at both doses
“Subcutaneous administration of 0, 50, or 150 mg/kg UCB7665 every 3 days to pregnant female cynomolgus monkeys from gestational day (GD) 20 through parturition caused embryonic losses in 3 of 19 females at both doses.”
Safety pharmacology
Incorporated into 4- and 13-week monkey studies; no cardiovascular, neurobehavioral or respiratory effects
“No stand-alone safety pharmacology studies were conducted. There were no test article-related effects on cardiovascular, neurobehavioral, or respiratory (no plethysmography) safety pharmacology parameters that were incorporated into the 4- and 13-week general toxicity studies.”
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 Rystiggo 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 monoclonal antibodies 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 adverse effects up to 150 mg/kg SC every 3 days for 4, 13 and 26 weeks; reduced IgG, total protein and albumin (pharmacology) (FDA integrated review, p. 91)
NOAEL / key findings
No adverse effects up to 150 mg/kg SC every 3 days for 4, 13 and 26 weeks; reduced IgG, total protein and albumin (pharmacology)
“No adverse effects were seen in male and female cynomolgus monkeys administered subcutaneous (SC) doses of up to 150 mg/kg UCB7665 every 3 days for 4, 13, and 26 weeks.”
Risksopen answer page →
Immune & cytokine safety
No cytokine release in any of four in vitro assay formats
“All assays, conducted using appropriate positive and negative controls, did not indicate the potential for stimulation of UCB7665-induced cytokine release.”
Biodistribution & persistence
TCR in human and cynomolgus tissues: generally similar staining patterns between species
“The staining patterns were generally similar between species; however, the study report did not specify whether specific binding was membranous or cytoplasmic.”
Modality-specific risk
Infection risk from FcRn blockade reducing circulating IgG
“Infections were of special interest because Fc receptor inhibition results in a reduction of circulating IgG, which potentially increases the risk of infection.”