Regulatory Experience Assessing the Carcinogenic Potential of a Monoclonal Antibody Inhibiting PCSK9, Bococizumab, Including a 2-Year Carcinogenicity Study in Rats
| Autor: | Bernard S. Buetow, Gregg D Cappon, Laura M. Aschenbrenner, Lawrence Updyke, Vince R. Torti, Mark Evans, Shana R. Dalton, Steven Bailey, Christopher J. Bowman |
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| Rok vydání: | 2022 |
| Předmět: | |
| Zdroj: | International Journal of Toxicology. 41:389-401 |
| ISSN: | 1092-874X 1091-5818 |
| DOI: | 10.1177/10915818221106397 |
| Popis: | 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data from another anti-PCSK9 antibody, RN317, with a similar low tumor incidence (unrelated to RN317), the U.S. FDA rescinded the bococizumab carcinogenicity study waiver and requested a full 2-year rat carcinogenicity study be conducted.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. |
| Databáze: | OpenAIRE |
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