Oral cell cycle inhibitor has mono and combined therapy potential

Eli Lilly and Company has announced the FDA granted the submission Priority Review acceptance of its New Drug Application (NDA) for abemaciclib, the company’s cyclin-dependent kinase (CDK)4 & 6 oral cell cycle inhibitor. With the designation, abemaciclib is on accelerated path to approval—one that included regulators designating the cell cycle inhibitor a Breakthrough Therapy in 2015.

“A drug that receives Breakthrough Therapy Designation may be eligible for Priority Review,” said Lilly of the FDA program that aims to speed review of drugs that represent significant advances 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.” Lilly said it anticipates FDA action on this application in the first quarter of 2018. Similarly, the company intends to submit abemaciclib to EMA and Japanese regulators later this year.

The NDA for abemaciclib covers two indications, the first is a monotherapy for advanced breast cancer patients who are hormone-receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-) and have had prior endocrine therapy (plus chemotherapy for metastatic disease). The second indication is abemaciclib in combination with fulvestrant in women with advanced HR+ and HER2- breast cancer with disease progression after endocrine therapy.

With nearly 1.7 million new cases diagnosed in 2012, Lilly said advanced breast cancer is the most common cancer among women. In many cancers, including advanced breast cancers, Lilly said uncontrolled cell growth stems from poor cell cycle regulation because of increased CDK4 and CDK6 signaling. Abemaciclib, according to Lilly, is designed to block the growth of cancer cells by “specifically inhibiting cyclin-dependent kinases, CDK4 and CDK6. The drug has demonstrated, “most active against Cyclin D1 and CDK4 in cell-free enzymatic assays.” Cyclin D1/CDK4 can also promote “phosphorylation of the retinoblastoma protein (Rb), cell proliferation and tumor growth,” which can induce cell cycle arrest.

"Breast cancer is a complex disease, and the need still exists for new treatment options as patients face a significant disease burden,” commented Levi Garraway, Lilly Oncology’s Senior Vice President, Global Development and Medical Affairs. “We look forward to working with the FDA and bringing this important potential treatment option to patients as soon as possible."