Eli Lilly and Company has announced that the US Food and Drug Administration (FDA) has granted Priority Review designation for its New Drug Application (NDA) for Verzenio (abemaciclib), a cyclin-dependent kinase (CDK)4 & 6 inhibitor. The NDA was based upon the positive interim results from MONARCH 3, a study of abemaciclib in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of women with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. The results were presented at the European Society for Medical Oncology (ESMO) 2017 Congress, and recently published in the Journal of Clinical Oncology.
"On the heels of our recent FDA approval of Verzenio, we are pleased with this important step forward in the agency's consideration to expand the use of Verzenio in metastatic breast cancer," said Levi Garraway, M.D., Ph.D., senior vice president, global development and medical affairs, Lilly Oncology. "We look forward to ongoing collaboration with the FDA to advance this important treatment across the spectrum of care for patients living with advanced or metastatic breast cancer."
Priority Review aims to expedite the review of applications for drugs that, if approved, would represent a significant advance in treatment. With Priority Review of a new drug, the FDA's goal is to take action within eight months of receiving an application, compared with the standard review timeframe of 12 months. In the third quarter of 2017, Lilly completed EU and Japan regulatory submissions for abemaciclib.
Verzenio (abemaciclib) is an inhibitor of CDK4 and CDK6, which are activated by binding to D-cyclins. In estrogen receptor-positive (ER+) breast cancer cell lines, cyclin D1 and CDK4 & 6 promote phosphorylation of the retinoblastoma protein (Rb), cell cycle progression, and cell proliferation.
Verzenio disrupts the cell cycle. Preclinically, Verzenio dosed daily without interruption as a single agent or in combination with antiestrogens resulted in reduction of tumor size. In vitro, continuous exposure to Verzenio inhibited Rb phosphorylation and blocked progression from G1 to S phase of the cell cycle, resulting in senescence and apoptosis (cell death). Inhibiting CDK4 & 6 in healthy cells can result in side effects, some of which may be serious. Clinical evidence also suggests that Verzenio crosses the blood-brain barrier.