Pfizer and Astellas Seek FDA Approval to Expand Xtandi Use in mHSPC with Priority Review Granted

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Pfizer and its partner Astellas recently announced that the U.S. FDA has accepted a supplemental new drug application (sNDA) for Xtandi (enzalutamide) for male patients with metastatic hormone-sensitive prostate cancer (mHSPC) and granted it priority review, with a PDUFA target date in the fourth quarter of 2019.

Currently, Xtandi is approved in the United States for the treatment of castration-resistant prostate cancer (CRPC) and has become a standard-of-care medication for clinical CRPC. If this supplemental New Drug Application (sNDA) is approved, it will further unlock the potential of Xtandi.

This sNDA is based on data from two pivotal Phase III clinical studies (ARCHES and ENZAMET). The ARCHES study enrolled a total of 1,150 patients with metastatic hormone-sensitive prostate cancer (mHSPC) to evaluate the efficacy and safety of Xtandi combined with androgen deprivation therapy (ADT). The results were presented in February 2019 at the American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium and published in July in the Journal of Clinical Oncology. The results demonstrated that the primary endpoint was met: compared with placebo plus ADT, the Xtandi plus ADT regimen significantly reduced the risk of radiographic progression by 61% in patients with mHSPC.

The ENZAMET study enrolled a total of 1,125 patients with metastatic hormone-sensitive prostate cancer (mHSPC) to evaluate the efficacy and safety of Xtandi plus androgen deprivation therapy (ADT), compared against a positive control regimen of ADT plus standard nonsteroidal antiandrogen (NSAA) therapy (bicalutamide, nilutamide, or flutamide). The results were presented this June at the American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in The New England Journal of Medicine. The study met its primary endpoint: compared with the standard NSAA plus ADT regimen, the Xtandi plus ADT regimen significantly reduced the risk of death by 33% in patients with mHSPC. The 3-year overall survival rate was 80% in the Xtandi plus ADT group versus 72% in the standard NSAA plus ADT group.

The safety analysis results from the two studies were consistent with those from previous clinical trials of Xtandi in the treatment of CRPC. Based on these findings, Pfizer and Astellas have also submitted regulatory applications in the European Union and Japan to seek an expanded indication for Xtandi in the treatment of male patients with mHSPC.

Xtandi is a once-daily oral androgen receptor signaling inhibitor that inhibits multiple steps in the androgen receptor signaling pathway, designed to interfere with the ability of testosterone to bind to prostate cancer cells. It has been shown to reduce cancer cell growth and induce tumor cell death.

Xtandi was first approved for marketing in 2012 for the treatment of metastatic castration-resistant prostate cancer (mCRPC). In 2018, Xtandi received further approval in the United States and Japan for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC), and in the European Union for the treatment of high-risk nmCRPC.

Currently, Xtandi and Johnson & Johnson’s Zytiga are the two best-selling products in the prostate cancer field. Zytiga was launched in 2011, and although Xtandi entered the market one year later, its sales grew rapidly, surpassing Zytiga in 2017. In 2018, Zytiga generated $3.5 billion in sales, while Xtandi reached $3.624 billion. EvaluatePharma predicts that the nmCRPC indication will serve as a key catalyst for Xtandi’s growth, with sales expected to reach $4.467 billion by 2024, making it a blockbuster product in the field of prostate cancer treatment.

The fate of Zytiga may be poised for a dramatic shift. In October last year, the U.S. District Court for the District of New Jersey ruled that U.S. Patent No. 8,822,438 for Zytiga was invalid; this patent was originally set to expire in 2027. Currently, patent litigation concerning Zytiga is ongoing in the United States. If the patent is ultimately declared invalid, Zytiga will face severe repercussions, with its sales expected to plummet precipitously following the market entry of generic versions.

In addition to the two aforementioned drugs, newly approved therapies for prostate cancer in recent years include Johnson & Johnson’s Erleada and Bayer’s Nubeqa. Erleada, a next-generation androgen receptor inhibitor approved in 2018, was the first drug authorized in the United States and Europe for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC). The application for its new indication in metastatic castration-sensitive prostate cancer (mCSPC) has entered the FDA’s Real-Time Oncology Review (RTOR) program. The industry holds strong optimism regarding Erleada’s commercial prospects; EvaluatePharma predicts that the drug’s global sales will reach $2.115 billion in 2024. Nubeqa, an oral non-steroidal androgen receptor inhibitor, received FDA approval in late July of this year for the treatment of nmCRPC, while its development for metastatic hormone-sensitive prostate cancer (mHSPC) has advanced to Phase III clinical trials. Unlike other existing nmCRPC medications, Nubeqa does not cross the blood-brain barrier, thereby resulting in fewer potential drug interactions and central nervous system side effects.

Furthermore, the PARP inhibitors Zejula and Lynparza have demonstrated robust efficacy data in BRCA-mutated prostate cancer and homologous recombination repair-deficient prostate cancer, respectively. In the realm of immunotherapy, BMS’s combination therapy Opdivo + Yervoy and Merck’s Keytruda (combined with chemotherapy, Lynparza, and Xtandi, respectively) have yielded strong data in patients with refractory metastatic castration-resistant prostate cancer (mCRPC).

It is foreseeable that the field of prostate cancer will soon witness a blossoming of diverse therapeutic advances: androgen deprivation therapy, targeted agents, and immunotherapy will provide multiple important new treatment options for patients with various types of prostate cancer.

Reference Source:

1、U.S. FDA GRANTS XTANDI® (ENZALUTAMIDE) APPLICATION PRIORITY REVIEW FOR THE TREATMENT OF MEN WITH METASTATIC HORMONE-SENSITIVE PROSTATE CANCER

2. Articles on Sina Medicine Website