Regulatory Experience Assessing the Carcinogenic Potential of a Monoclonal Antibody Inhibiting PCSK9, Bococizumab, Including a 2-Year Carcinogenicity Study in Rats.
Int J Toxicol
; 41(5): 389-401, 2022.
Article
en En
| MEDLINE
| ID: mdl-35672934
ABSTRACT
Bococizumab is an anti-PCSK9 monoclonal antibody that was intended for the treatment of hypercholesterolemia. After reviewing the 6-month rat toxicity study data, in which there was a low spontaneous tumor incidence, unrelated to bococizumab administration, the U.S. FDA granted a carcinogenicity waiver request based on a weight-of-evidence assessment of low carcinogenic risk. Subsequently, after reviewing 6-month rat toxicity study data from another anti-PCSK9 antibody, RN317, with a similar low tumor incidence (unrelated to RN317), the U.S. FDA rescinded the bococizumab carcinogenicity study waiver and requested a full 2-year rat carcinogenicity study be conducted. The resulting 2-year carcinogenicity study demonstrated no bococizumab-related increase in tumors, confirming the weight-of-evidence evaluation and alleviating concerns regarding the carcinogenic potential. Here we report the scientific and regulatory background that led to the request for a rat carcinogenicity study, the feedback on the design of the carcinogenicity study, and the results from this study which affirmed the original weight-of-evidence assessment of low carcinogenic risk.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Carcinógenos
/
Hipercolesterolemia
Límite:
Animals
Idioma:
En
Revista:
Int J Toxicol
Asunto de la revista:
TOXICOLOGIA
Año:
2022
Tipo del documento:
Article
País de afiliación:
Estados Unidos