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.
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(unrelated to RN317), the U.S. FDA rescinded the bococizumab carcinogenicity study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.