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- Title
Successful Integration of Nonclinical and Clinical Findings in Interpreting the Clinical Relevance of Rodent Neoplasia with a New Chemical Entity.
- Authors
Johnson, Mark D.; Louden, Calvert; De Jonghe, Sandra; Ways, Kirk; Mamidi, Rao N. V. S.; Proctor, James
- Abstract
Canagliflozin, a sodium glucose co-transporter 2 (SGLT2) inhibitor, has been developed for the treatment of adults with type 2 diabetes mellitus (T2DM). During the phase 3 program, treatment-related pheochromocytomas, renal tubular tumors, and testicular Leydig cell tumors were reported in the 2-year rat toxicology study. Treatment-related tumors were not seen in the 2-year mouse study. A cross-functional, mechanism-based approach was undertaken to determine whether the mechanisms responsible for tumorigenesis in the rat were of relevance to humans. Based on findings from nonclinical and clinical studies, the treatment-related tumors observed in rats were not deemed to be of clinical relevance. Here, we describe the scientific and regulatory journey from learning of the 2-year rat study findings to the approval of canagliflozin for the treatment of T2DM.
- Subjects
SODIUM-glucose cotransporters; CANAGLIFLOZIN; CARCINOGENICITY; ANIMAL models in research; TYPE 2 diabetes treatment; PHEOCHROMOCYTOMA; LEYDIG cell tumors
- Publication
Toxicologic Pathology, 2015, Vol 43, Issue 1, p48
- ISSN
0192-6233
- Publication type
Article
- DOI
10.1177/0192623314557179