Ribociclib Granted Breakthrough Therapy Designation for HER2-Negative Breast Cancer

August 11, 2016

The FDA has granted Breakthrough Therapy Designation to Novartis for ribociclib (LEE011), in combination with letrozole (Femara), for treating hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced or metastatic breast cancer.

The US Food and Drug Administration (FDA) has granted Breakthrough Therapy Designation to Novartis for ribociclib (LEE011), in combination with letrozole (Femara), for treating hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) advanced or metastatic breast cancer. Ribociclib is a selective cyclin dependent kinase (CDK4/6) inhibitor and letrozole is a nonsteroidal aromatase inhibitor, which lowers estrogen production, and is used to treat breast cancer in postmenopausal women.

The growth of ER-positive breast cancer is dependent on cyclin D1, and thus there is role for CDK4/6 inhibition. Currently, palbociclib (Ibrance) is the only CDK4/6 inhibitor FDA-approved for postmenopausal, ER-positive, HER2-negative metastatic breast cancer.

The phase III MONALEESA-2 trial was conducted at 294 clinical trial sites globally and randomized 668 patients in a 1:1 ratio stratified by the presence of liver and/or lung metastases. Patients received ribociclib 600 mg/daily (3 weeks on and 1 week off), or placebo, in combination with letrozole 2.5 mg/daily per the approved label.

Novartis' trial of ribociclib in combination with letrozole in postmenopausal women who had received no prior therapy for their advanced disease met the primary endpoint of clinically meaningful improvement in progression-free survival (PFS).

The most common all grade adverse events were neutropenia (85%), nausea (39%), leukopenia (39%), fatigue (23%), anemia (23%), lymphopenia (23%).  

The FDA's Breakthrough Therapy Designation speed up the development and review of new therapies that treat serious or life-threatening conditions, if the therapy has demonstrated substantial improvement over an available therapy on at least one clinically significant endpoint. The designation includes all of the Fast Track program features, as well as more intensive FDA guidance on an efficient drug development program.

"Despite advancements in treatment, an estimated 40,000 individuals in the United States die each year from advanced breast cancer," said Alessandro Riva, MD, Global Head, Oncology Development and Medical Affairs, Novartis Oncology in a news release. "This designation shows the potential of LEE011, and we look forward to close collaboration with the FDA and the advanced breast cancer community to provide a new treatment option for women living with HR+/HER2- advanced breast cancer as quickly as possible."