FDA Grants Priority Review for Abemaciclib in Advanced Breast Cancer

New Drug Application submission is based on the MONARCH 1 and MONARCH 2 studies

On 10 July 2017, Eli Lilly and Company announced that the US Food and Drug Administration (FDA) has accepted and filed its New Drug Application (NDA) for abemaciclib, a cyclin-dependent kinase (CDK)4/6 inhibitor, and given the NDA a Priority Review designation. The NDA includes the company's submission of abemaciclib for two indications: abemaciclib monotherapy for patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer who had prior endocrine therapy and chemotherapy for metastatic disease; and for abemaciclib in combination with fulvestrant in women with HR-positive, HER2-negative advanced breast cancer who had disease progression following endocrine therapy. This submission is based on the MONARCH 1 and MONARCH 2 studies, respectively.

In 2015, the FDA granted abemaciclib Breakthrough Therapy Designation based on data from the breast cancer cohort expansion of the phase I trial, JPBA, which studied the efficacy and safety of abemaciclib in women with advanced or metastatic breast cancer. A drug that receives Breakthrough Therapy Designation may be eligible for Priority Review, which 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.

Lilly is working closely with the FDA and anticipates agency action on this application in the first quarter of 2018. In addition, Lilly intends to submit abemaciclib to European regulators in the third quarter of 2017 and to Japanese regulators before the end of 2017.

In many cancers, uncontrolled cell growth arises from a loss of cell cycle regulation due to increased signalling from CDK4 and CDK6. Abemaciclib (LY2835219) is an investigational, oral cell cycle inhibitor, designed to block the growth of cancer cells by specifically inhibiting CDK4 and CDK6, and was most active against Cyclin D1 and CDK4 in cell-free enzymatic assays. In breast cancer, Cyclin D1/CDK4 has been shown to promote phosphorylation of the retinoblastoma protein (Rb), cell proliferation and tumour growth. In HR-positive breast cancer cell lines, sustained target inhibition by abemaciclib reduced phosphorylation of Rb, inducing cell cycle arrest.

Abemaciclib is evaluated in the comprehensive MONARCH clinical programme, which includes the following studies:

  • MONARCH 1: A global phase II study evaluating the efficacy and safety of abemaciclib monotherapy in patients with HR-positive, HER2-negative advanced breast cancer who had prior endocrine therapy and chemotherapy for metastatic disease.
  • MONARCH 2: A global phase III study evaluating the efficacy and safety of abemaciclib, in combination with fulvestrant, in patients with HR-positive, HER2-negative advanced breast cancer who progressed on endocrine therapy.
  • MONARCH 3: A global phase III study evaluating the efficacy and safety of abemaciclib, in combination with an aromatase inhibitor, as initial endocrine-based therapy for postmenopausal women with HR-positive, HER2-negative advanced breast cancer who have had no prior systemic treatment for advanced disease.
  • monarcHER:A global phase II study evaluating abemaciclib plus trastuzumab (with or without fulvestrant) in women with HR-positive, HER2-positive advanced breast cancer.
  • MONARCH plus: A phase III study evaluating the efficacy and safety of abemaciclib, in combination with endocrine therapies, to support registration in China. 
  • neoMONARCH:A phase II study evaluating abemaciclib in the neoadjuvant setting, alone or in combination with the non-steroidal aromatase-inhibitor anastrozole, in postmenopausal women with previously untreated early stage HR-positive, HER2-negative breast cancer.
  • monarchE: A global phase III study evaluating the efficacy and safety of abemaciclib in the adjuvant setting in patients with high-risk, early breast cancer.

In addition to its current MONARCH clinical trials evaluating abemaciclib in breast cancer, a phase III trial of abemaciclib in lung cancer is also underway.

The Lilly’s press release contains forward-looking statements about abemaciclib as a potential treatment for patients with breast cancer and reflects Lilly's current beliefs.