The recent first global approval of ribociclib has been reviewed in detail in the First Global Approval report in Adis journal Drugs, based on the development milestones tracked in AdisInsight.
In March 2017, ribociclib (Kisqali®), developed by Novartis in collaboration with Astex Pharmaceuticals, received its first global approval in the USA for the first-line treatment, in combination with an aromatase inhibitor, of advanced breast cancer – specifically as initial endocrine-based therapy for the treatment of postmenopausal women with hormone receptor (HR) positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer.1 The FDA granted this application a priority review and breakthrough therapy designation. It has also been submitted for approval in the EU for the same indication.
Ribociclib is an oral, small-molecule inhibitor of cyclin-dependent kinase (CDK) 4 and 6 that inhibits the involvement of CDKs in cell cycle progression and cellular proliferation, resulting in G1 phase cell-cycle arrest. This is thought to help overcome the resistance developed to the hormonal therapy used to treat advanced breast cancer.
It is estimated that more than 250,000 women in the US will be diagnosed with breast cancer in 2017, making it the most common form of cancer in the country.2
This approval is the first to follow that of the first-in-class palbociclib (Ibrance®) in February 2015, developed by Pfizer.3 These next-generation CDK inhibitors have been designed to be more selective, hopefully avoiding some of the toxicities and muted efficacy seen with earlier non-specific CDK inhibitors. Although there are no direct head-to-head comparisons, late-stage study results indicate similar efficacy for the two drugs. However, ribociclib has been shown to prolong the QT interval in a concentration-dependent manner, so will require close monitoring of patients.
Gabriel N. Hortobagyi, MD, Professor of Medicine, Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center and the Principal Investigator in the pivotal trial4, 5 of ribociclib leading to its approval states that:
“combination therapy with a CDK4/6 inhibitor like ribociclib and an aromatase inhibitor should be a new standard of care for initial treatment of HR+ advanced breast cancer.” 6
Ribociclib is also under further Phase III investigation in breast cancer and is being evaluated in phase I or II trials for various solid tumour types and haematological malignancies.
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