Regulatory Experience Assessing the Carcinogenic Potential of a Monoclonal Antibody Inhibiting PCSK9, Bococizumab, Including a 2-Year Carcinogenicity Study in Rats

Buetow, Bernard S. ✉; Cappon, Gregg D.; Aschenbrenner, Laura M.; Updyke, Lawrence; Torti, Vince R.; Evans, Mark; Dalton, Shana R.; Bailey, Steven; Bowman, Christopher J.

Angol nyelvű Szakcikk (Folyóiratcikk) Tudományos
Megjelent: INTERNATIONAL JOURNAL OF TOXICOLOGY 1091-5818 1092-874X 41 (5) pp. 389-401 Paper: 10915818221106397 2022
  • SJR Scopus - Toxicology: Q3
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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data from another anti-PCSK9 antibody, RN317, with a similar low tumor incidence (unrelated to RN317), the U.S. FDA rescinded the bococizumab carcinogenicity study waiver and requested a full 2-year rat carcinogenicity study be conducted.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.
Hivatkozás stílusok: IEEEACMAPAChicagoHarvardCSLMásolásNyomtatás
2025-01-03 16:29