Request for Xtandi to Treat Metastatic Hormone-sensitive Prostate Cancer Before FDA

The U.S. Food and Drug Administration (FDA) has agreed to review Astellas Pharma and Pfizer‘s application for Xtandi (enzalutamide), requesting its approved use be expanded to include men whose metastatic prostate cancer still responds to hormone therapy.

The supplemental new drug application, covering men with metastatic hormone-sensitive prostate cancer (mHSPC) in the U.S., was granted priority review. A decision is expected in the final months of 2019.

“We are pleased to receive the priority review designation, which reflects the need for more treatment options for men living with metastatic hormone-sensitive prostate cancer,” Chris Boshoff, MD, PhD, chief development officer of Oncology at Pfizer Global Product Development, said in a press release. “The submission is supported by a strong data package, including two Phase 3 trials investigating Xtandi in men living with this form of prostate cancer.”

Xtandi, developed by Pfizer and Astellas Pharma, is a form of hormone therapy that aims to prevent male hormones from sending chemical signals that stimulate cancer growth; it does so by blocking the activity of their receptor. The treatment was developed for advanced forms of prostate cancer.

The FDA approved Xtandi’s use in men with late-stage castration-resistant prostate cancer (CRPC) in 2012. Now, Pfizer and Astellas are requesting that its label also include men with mHSPC.

The submission was based on data from two Phase 3 trials — ARCHES (NCT02677896) and ENZAMET (NCT02446405) — assessing the safety and efficacy of Xtandi in combination with androgen deprivation therapy (ADT), compared to ADT alone, or with a standard nonsteroidal anti-androgen therapy in this patient group.

Findings from ARCHES, a company sponsored trial, were recently published in The Journal of Clinical Oncology and presented at the 2019 Genitourinary Cancers Symposium (ASCO GU) in San Francisco.

These reported results showed that ARCHES met its primary goal, with Xtandi plus ADT lowering the risk of radiographic progression or death by 61% in treated patients with mHSPC, compared to those given ADT and a placebo. The frequency of severe side effects was similar in patients in both groups.

Results from ENZAMET, a trial led by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) and sponsored by the University of Sydney, were published in The New England Journal of Medicine and presented at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting in Chicago.

ENZAMET also met its primary overall survival goals, reported findings showed, with 80% of mHSPC patients given Xtandi in combination with ADT surviving more than three years, compared to 72% of those given ADT plus a nonsteroidal antiandrogen therapy (bicalutamide, nilutamide or flutamide). Xtandi’s safety profile was consistent with data from previous clinical trials in men with CRPC.

“The complementary data from the ARCHES and ENZAMET trials in men with mHSPC take us another step closer to understanding Xtandi’s full potential in helping address unmet needs in prostate cancer,” said Andrew Krivoshik, MD, PhD, senior vice president and head of the Oncology Therapeutic Area at Astellas. “Xtandi is a current standard of care in castration-resistant prostate cancer and we look forward to working with the FDA to potentially make Xtandi available to men earlier in their prostate cancer journey.”

Data from both trials was also used to in similar expanded label requests to the European Medicines Agency (EMA) and to the Pharmaceuticals and Medical Devices Agency (PMDA) in Japan.