CDK4/6 Inhibitor LEE011 (Ribociclib) Receives FDA Breakthrough Therapy Designation

Designation considers the first-line treatment for hormone receptor-positive/HER2-negative advanced breast cancer

On 3 August 2016 Novartis announced that the US Food and Drug Administration (FDA) has granted Breakthrough Therapy designation to LEE011 (ribociclib), in combination with letrozole, for the treatment of hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. LEE011 is a selective cyclin dependent kinase (CDK4/6) inhibitor.

The Breakthrough Therapy designation is based primarily on positive results of the phase III MONALEESA-2 trial of LEE011 in combination with letrozole in postmenopausal women who had received no prior therapy for their advanced disease. The MONALEESA-2 trial met the primary endpoint of clinically meaningful improvement in progression-free survival (PFS) at a pre-planned interim analysis. Results of this study will be presented at an upcoming medical congress and will form the basis of regulatory discussions in the US, Europe and other countries for use in this indication.

Up to one-third of patients with early-stage breast cancer will subsequently develop metastatic disease. Survival rates for women living with advanced breast cancer are lower than those for women with earlier stage disease. The 5-year relative survival rate for stage III breast cancer is approximately 72%, while metastatic, stage IV breast cancer has a 5-year relative survival rate of approximately 22%.

According to the FDA, Breakthrough Therapy designation is intended to expedite the development and review of potential new medicines 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 programme features, as well as more intensive FDA guidance on an efficient drug development programme.

LEE011 has been studied in non-clinical models and is currently being evaluated in combination with additional endocrine agents as part of the MONALEESA (Mammary ONcology Assessment of LEE011's Efficacy and SAfety) clinical trial programme. LEE011 is not approved for any indication in any market at this time.

MONALEESA-2 is a phase III randomised, double blind, placebo controlled, multicentre global registration trial to evaluate the safety and efficacy of LEE011 in combination with letrozole compared to letrozole alone in postmenopausal women with hormone receptor-positive/HER2-negative advanced breast cancer who received no prior therapy for their advanced breast cancer. MONALEESA-2 met the primary endpoint of clinically meaningful improvement in PFS at the pre-planned interim analysis and is continuing to assess overall survival data.

MONALEESA-3 is a trial evaluating LEE011 in combination with fulvestrant compared to fulvestrant alone in men and post-menopausal women with hormone receptor-positive/HER2-negative advanced breast cancer who have received no or a maximum of one prior endocrine therapy. MONALEESA-3 is fully enrolled.

MONALEESA-7 is a trial investigating LEE011 in combination with endocrine therapy and goserelin compared to endocrine therapy and goserelin alone in pre-menopausal women with hormone receptor-positive/HER2-negative advanced breast cancer who have not previously received endocrine therapy. MONALEESA-7 is fully enrolled and is the only phase III study that focuses solely on pre and perimenopausal women with advanced breast cancer.

LEE011 was developed by Novartis Institutes for BioMedical Research under a research collaboration with Astex Pharmaceuticals.

The press release from Novartis contains forward-looking statements.