Nonclinical safety of tildrakizumab, a humanized anti-IL-23p19 monoclonal antibody, in nonhuman primates.
Regul Toxicol Pharmacol
; 108: 104476, 2019 Nov.
Article
em En
| MEDLINE
| ID: mdl-31536773
ABSTRACT
Tildrakizumab (also known as MK-3222), is a high-affinity, humanized, immunoglobin G1κ monoclonal antibody targeting the p19 subunit of interleukin-23 recently approved for the treatment of moderate to severe plaque psoriasis in the US, Europe, and Australia. The safety profile of tildrakizumab was characterized in nonclinical studies using a pharmacologically relevant cynomolgus monkey model. In repeat-dose toxicity studies, cynomolgus monkeys were chronically treated with subcutaneous (SC) injections of 100â¯mg/kg of tildrakizumab every 2 weeks up to 9 months. Tildrakizumab was well tolerated, with no toxicological findings (including assessment of reproductive organs; hormonal effects; and cardiovascular, respiratory, and central nervous system function) at systemic exposures approximately 90 times higher than the recommended human dose of 100â¯mg. An embryofetal developmental study conducted in pregnant monkeys revealed no treatment-related effects to the developing fetus following SC administration of tildrakizumab 100â¯mg/kg. In a pre- and postnatal development study, 2 neonatal deaths due to potential viral infection at 100â¯mg/kg were considered of uncertain relationship to the treatment based on a lack of historical data on the occurrence of viral infection in neonate cynomolgus monkeys. The results of this comprehensive nonclinical safety program support the safe use of tildrakizumab.
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MEDLINE
Assunto principal:
Anticorpos Monoclonais Humanizados
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En
Ano de publicação:
2019
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Article