Pfizer Submits New Indication NDA for CDK 4/6 Inhibitor Palbociclib in China

On December 7, the Center for Drug Evaluation (CDE) under China’s National Medical Products Administration announced on its website that it had accepted two new drug marketing applications submitted by Pfizer for the CDK4/6 inhibitor palbociclib. According to a press release previously issued by Pfizer, palbociclib is the world’s first CDK4/6 inhibitor. It has received Breakthrough Therapy designation from the U.S. Food and Drug Administration (FDA) and was approved for marketing in the United States and China in 2015 and 2018, respectively, for the treatment of advanced breast cancer. Based on publicly available information, the specific new indications included in this submission have not yet been determined.

Source: CDE Official Website

According to an earlier press release from Pfizer, palbociclib, the world’s first selective CDK4/6 inhibitor launched by the company, blocks tumor cell proliferation by inhibiting CDK4/6 and restoring cell cycle control. The company’s 2019 financial report showed that palbociclib generated sales as high as $4.961 billion in 2019, making it one of the key drivers of Pfizer’s performance growth, which underscores the substantial clinical demand for this drug.

In China, palbociclib was approved for marketing in 2018, with the indication of: in combination with aromatase inhibitors for the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) locally advanced or metastatic breast cancer, as initial endocrine therapy for postmenopausal female patients. Global registration studies have shown that the median progression-free survival (PFS) of HR+/HER2- breast cancer patients treated with palbociclib in combination with letrozole is up to 24.8 months.

The submission of a new indication marketing application for palbociclib in China means that this innovative therapy is expected to benefit more cancer patients. According to public information, palbociclib has also been approved in the United States for female breast cancer patients whose disease progresses after endocrine therapy, as well as for male patients with advanced breast cancer.

Among these, palbociclib was approved by the FDA in November 2017 for use in combination with fulvestrant to treat postmenopausal women and men with HR+/HER2- advanced or metastatic breast cancer whose disease had progressed following endocrine therapy. In the Phase 3 clinical trial named MONARCH 2, patients receiving fulvestrant 500 mg plus palbociclib 150 mg demonstrated a statistically significant improvement in investigator-assessed median progression-free survival (PFS) of 7.1 months compared to those receiving fulvestrant plus placebo (16.4 months vs. 9.3 months). The study met its primary endpoint of PFS, confirming that the combination therapy provides patients with another effective non-chemotherapy option for combating the disease.

Additionally, in April 2019, the FDA approved palbociclib in combination with an aromatase inhibitor or fulvestrant for the treatment of male patients with HR+/HER2- advanced or metastatic breast cancer. This approval was based on data from electronic health records and real-world post-marketing use of palbociclib in male patients. Analysis revealed that palbociclib demonstrated a similar safety profile in both male and female patients. This also implies that palbociclib holds promise for benefiting male breast cancer patients who have limited treatment options.

Breast cancer is the leading malignant tumor posing a serious threat to women's health worldwide. It is estimated that 90% of breast cancer cases are diagnosed at an early stage. The most common subtype is hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer, accounting for 70% of all breast cancer patients. Approximately 30% of patients diagnosed with early-stage HR+/HER2- breast cancer still face a risk of cancer recurrence. In contrast to the diverse treatment options available for early-stage breast cancer, the overall median survival for patients with advanced breast cancer is only 2–3 years, with a 5-year survival rate of approximately 20%, highlighting an urgent need for innovative therapeutic approaches.

It is worth noting that men can also develop breast cancer. However, due to the rarity of male breast cancer cases, conducting clinical trials for this population is challenging, which has, to some extent, delayed their access to innovative therapies. The approval of palbociclib has brought new treatment options for these patients.

In addition to breast cancer, palbociclib is being investigated for new indications in clinical studies. Notably, its combination with Roche’s PI3Kα inhibitor and endocrine therapy has demonstrated promising efficacy in a Phase 1/1b clinical trial involving patients with PIK3CA-mutated solid tumors. A Phase 3 clinical trial evaluating this combination regimen in patients with HR+/HER2- metastatic breast cancer harboring PIK3CA mutations was initiated in the first quarter of this year.

References:

[1] Center for Drug Evaluation, National Medical Products Administration of China (CDE). Retrieved Dec 7, 2020, from http://www.cde.org.cn/news.do?method=changePage&pageName=service&frameStr=21#

[2] Pfizer uses real-world data to score Ibrance breast cancer nod in males. Retrieved Apr5, 2019, from https://www.fiercepharma.com/pharma/pfizer-uses-real-world-data-to-score-ibrance-breast-cancer-nod-males

[3] Faslodex receives US FDA approval for the treatment of advanced breast cancer in combination with abemaciclib. Retrieved Nov 16, 2017, from AstraZeneca's official website

Source: Yiyao Guanlan

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