Pfizer Inc. has announced that the New Drug Application (NDA) for palbociclib has been accepted for filing and granted Priority Review by the United States Food and Drug Administration (FDA).
This NDA will depend on the FDA’s approval of palbociclib, in combination with letrozole, as a first-line treatment for 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.
Palbociclib is an investigational oral drug that inhibits cyclin-dependent kinases (CDKs) 4 and 6. This blockade allows a tight control of the cell cycle and inhibits tumor cell proliferation, since the majority of cancers exhibit an over-activation of these two cyclins, resulting in uncontrolled tumor growth.
Data gathered from different preclinical studies has demonstrated that in ER+ breast cancer cell lines that have an increased activity of CDK4/6, inhibition of both these cyclins together with ER signaling can stop tumor cell proliferation.
Pfizer’s NDA submission is based on the promising results of the PALOMA-1 clinical study, a randomized, Phase 2 trial comparing 125mg of palbociclib once daily for three out of four weeks in repeated cycles, plus letrozole versus 2.5 mg of letrozole alone once daily on a continuous regimen, in post-menopausal women with ER+, HER2- advanced breast cancer.
This study was conducted in collaboration with the Jonsson Cancer Center’s Revlon/UCLA Women’s Cancer Research Program and set its primary endpoint to progression-free survival, which increased by 50% when patients received the combination therapy.
If palbociclib receives the FDA’s Priority Review status, which is only given to experimental drugs that can offer significant advances in treatment or may fill an unmet medical need, it will lead to an accelerated review time, from 10 months to 6 months.
The FDA has also determined that the Prescription Drug User Fee Act (PDUFA) goal date for a decision is April 13, 2015.
Back in April 2013, palbociclib received Breakthrough Therapy designation from the FDA, for the first-line systemic treatment of women with advanced or metastatic ER+, HER2- breast cancer.
“If approved as a first-line therapy in combination with letrozole, palbociclib will be an important new option for the thousands of women in the U.S. who are living with metastatic breast cancer,” Garry Nicholson, president, Pfizer Oncology, said in a company’s press release. “We look forward to continuing to work closely with the FDA through the review process.”
Just recently, Pfizer initiated a multi-center, open-label expanded access program (EAP) for palbociclib in the United States, where post-menopausal women with HR+, HER2- advanced breast cancer, eligible for letrozole therapy but not other palbociclib clinical trials, can be given palbociclib treatment.
For patients and healthcare professional who might be interested in learning more about the palbociclib EAP, information is available here (trial number: NCT02142868).