The FDA approved Novartis's ribociclib for the first-line treatment of hormone receptor (HR)+/HER2− advanced breast cancer in combination with an aromatase inhibitor. This is the second approval for the cyclin-dependent kinase 4 and 6 (CDK4/6) class of kinase inhibitors.

CDKs are crucial regulatory enzymes that control cell cycle transitions and therefore cell proliferation. Although CDK inhibitors have been in development since the 1990s, drug developers struggled with efficacy and toxicity issues until they focused on selective inhibition of CDK4 and CDK6.

Pfizer was first to market, with its 2015 accelerated approval of CDK4/6 inhibitor palbociclib for HR+/HER2− advanced breast cancer. Novartis now plans to compete in part by offering competitive and flexible pricing options. Analysts forecast global annual sales of up to US$1.7 billion for ribociclib, shows the Clarivate Analytics Cortellis database.

Both ribociclib and palbociclib are breakthrough therapy designees.

Despite blockbuster expectations for palbociclib and ribociclib, the development of many of the remaining CDK inhibitors appears to have stalled. One of the few remaining candidates under active development is Lilly's CDK4/6 inhibitor ademaciclib, which is in phase III trials for breast cancer and non-small-cell lung cancer and phase II trials for pancreatic cancer. Key issues holding up the field include uncertainty over how to define the tumour types that might benefit, how to optimize treatment schedules and how to combine these drugs with other therapeutics (Nat. Rev. Drug Discov. 14, 130–146; 2015).

Ribociclib was discovered as part of a structure-based drug discovery collaboration between Novartis and Astex Pharmaceuticals, a fragment-based drug discovery company that is now a subsidiary of Otsuka Pharmaceutical.