The FDA has accepted the new drug application (NDA) for ribociclib (LEE011, Novartis) and has granted the drug priority review for the first-line treatment of postmenopausal women with hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2–) advanced or metastatic breast cancer in combination with letrozole. The NDA was partly based on results from a phase 3 trial that showed that ribociclib plus letrozole reduced the risk of disease progression or death by 44% compared with letrozole alone (hazard ratio, 0.556; P = 0.00000329), significantly extending progression-free survival (PFS).
A priority review designation requires the FDA to take action on an application within six months of its filing date compared with 10 months under a standard review. The FDA grants priority review to applications for new drug candidates that treat serious conditions, such as advanced breast cancer, for which there is no cure, and that, if approved, would provide a significant improvement in treatment safety or efficacy.
Ribociclib is a selective cyclin-dependent kinase inhibitor, a class of drugs that helps slow the progression of cancer by inhibiting two proteins, cyclin-dependent kinase 4 and 6 (CDK4/6). These proteins, when overactivated in a cell, can allow cancer cells to grow and divide too quickly. Ribociclib is not approved for any indication in any market at this time.
Novartis is continuing to evaluate ribociclib through the MONALEESA (Mammary ONcology Assessment of LEE011’s Efficacy and SAfety) clinical trial program, which includes MONALEESA-2, MONALEESA-3, and MONALEESA-7. These studies are evaluating ribociclib in multiple endocrine-therapy combinations in a range of patients, including men and premenopausal women.
MONALEESA-2 is a phase 3, randomized, double-blind, placebo-controlled, global registration study designed to evaluate the safety and efficacy of ribociclib in combination with letrozole compared with that of letrozole alone in postmenopausal women with HR+/HER2– advanced breast cancer who had received no prior therapy for their breast cancer. The trial randomly assigned 668 subjects to receive either ribociclib 600 mg/daily (three weeks on and one week off) or placebo in combination with letrozole 2.5 mg/daily. The study’s primary endpoint is PFS. Secondary endpoints include overall survival, the overall response rate, the clinical benefit rate, health-related quality of life, safety, and tolerability.
The MONALEESA-3 trial is evaluating ribociclib in combination with fulvestrant compared with fulvestrant alone in men and postmenopausal women with HR+/HER2– advanced breast cancer who have received no or a maximum of one prior endocrine therapy.
The MONALEESA-7 trial is investigating ribociclib in combination with endocrine therapy and goserelin compared with endocrine therapy and goserelin alone in pre-menopausal women with HR+/HER2– advanced breast cancer who have not previously received endocrine therapy.
Both the MONALEESA-3 and MONALEESA-7 trials are fully enrolled.
Up to one-third of patients with early-stage breast cancer will subsequently develop metastatic disease. Advanced breast cancer comprises metastatic breast cancer (stage 4) and locally advanced breast cancer (stage 3). Survival rates for women with advanced breast cancer are lower than those for women with earlier-stage disease. The five-year relative survival rate for stage 3 breast cancer is approximately 72%, whereas metastatic (stage 4) breast cancer has a five-year relative survival rate of approximately 22%.
Source: Novartis; November 1, 2016.