Pfizer Inc. today announced it has completed the submission of a New Drug Application (NDA) to the United States Food and Drug Administration (FDA) for palbociclib. This NDA requests FDA approval of palbociclib, in combination with letrozole, for the treatment of postmenopausal women with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer who have not received previous systemic treatment for their advanced disease. The submission is based on the final results of PALOMA-1, a randomized, Phase 2 trial comparing palbociclib plus letrozole versus letrozole alone in this population of patients.
Palbociclib received Breakthrough Therapy designation from the FDA in April 2013, for the first-line systemic treatment of women with advanced or metastatic ER+, HER2- breast cancer. This designation was based on interim data from the PALOMA-1 trial.
The FDA has a 60-day filing review period to determine whether the NDA is complete and acceptable for filing. Pfizer will communicate the Agency’s decision.
“Today’s submission marks an important milestone for Pfizer and palbociclib, and a potential advance for women with advanced breast cancer,” said Garry Nicholson, President, Pfizer Oncology.
Palbociclib is an investigational oral targeted agent that selectively inhibits cyclin-dependent kinases (CDKs) 4 and 6 to regain cell cycle control and block tumor cell proliferation.
Loss of cell cycle control is a hallmark of cancer and CDK 4/6 are overactivated in numerous cancers, leading to loss of proliferative control.
CDK 4/6 are key regulators of the cell cycle that trigger cellular progression from growth phase (G1) into phases associated with DNA replication (S).
CDK 4/6, whose increased activity is frequent in estrogen receptor-positive (ER+) breast cancer (BC), are key downstream targets of ER signaling in ER+ BC.
Preclinical data suggest that dual inhibition of CDK 4/6 and ER signaling is synergistic, and it has been shown to stop growth of ER+ BC cell lines in the G1 phase.
Palbociclib is not approved for any indication in any market.