Regulatory Experience Assessing the Carcinogenic Potential of a Monoclonal Antibody Inhibiting PCSK9, Bococizumab, Including a 2-Year Carcinogenicity Study in Rats. (September 2022)

• Record Type: Journal Article
• Authors: Buetow, Bernard S.; Cappon, Gregg D; Aschenbrenner, Laura M.; Updyke, Lawrence; Torti, Vince R.; Evans, Mark; Dalton, Shana R.; Bailey, Steven; Bowman, Christopher J.
• Is Part Of: International journal of toxicology. Volume 41:Number 5(2022)
• Page Start: 389
• Page End: 401
• Publication Date: 2022-09
• Subjects: carcinogenicity -- monoclonal antibody -- Sprague Dawley rat -- PCSK9; Toxicology -- Periodicals; 615.9005
• DOI: 10.1177/10915818221106397
• Languages: English
• ISSNs: 1091-5818

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data from another anti-PCSK9 antibody, RN317, with a similar low tumor incidence (unrelated to RN317), the U.S. FDA rescinded the bococizumab carcinogenicity study waiver and requested a full 2-year rat carcinogenicity study be conducted.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.