Xtandi (Enzalutamide) Receives FDA Approval for Metastatic Castration-Sensitive Prostate Cancer; NMPA Approval in China Follows in Late November

December 17, 2019 /Bio ValleyBIOON/ --PfizerPfizer and its partner Astellas recently announced that the U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) for the prostate cancer drug Xtandi (Chinese brand name: Anketan; generic name: enzalutamide), for the treatment of male patients with metastatic hormone-sensitive prostate cancer (mHSPC). This indication was approved throughFDAapproved under the Priority Review Program.

Currently, Xtandi has been established as the standard-of-care medication for castration-resistant prostate cancer (CRPC). Since its initial approval in 2012, it has treated more than 420,000 patients worldwide. The approval of the indication for metastatic hormone-sensitive prostate cancer (mHSPC) means that clinicians can now offer Xtandi to male patients earlier in the treatment journey for advanced prostate cancer. It is estimated that there were 40,000 patients with metastatic castration-sensitive prostate cancer (mCSPC) in the United States in 2019. mCSPC indicates that the cancer has spread to other parts of the body but still responds to androgen-lowering drugs or surgical treatment.

With this new approval, Xtandi is now the first and onlyFDAProducts approved for the treatment of three distinct types of advanced prostate cancer: non-metastatic castration-resistant prostate cancer (CRPC), metastatic CRPC, and mCSPC.

Notably, in late November this year, Xtandi (enzalutamide) was approved in China for the treatment of adult patients with metastatic castration-resistant prostate cancer (mCRPC) who are asymptomatic or mildly symptomatic and have not received chemotherapy, following failure of androgen deprivation therapy (ADT). Prostate cancer is the second most common malignant tumor in men worldwide and has become the most common male urological malignancy in China.Tumor。

FDAApproval of Xtandi for the treatment of mCSPC was based on data from the randomized Phase III ARCHES study. The study enrolled a total of 1,150 patients with mHSPC. The results demonstrated that the study met its primary endpoint of radiographic progression-free survival (rPFS): compared with the placebo plus androgen deprivation therapy (ADT) arm, the Xtandi plus ADT arm showed a statistically significant 61% reduction in the risk of radiographic progression (HR=0.39 [95% CI: 0.30–0.50]; p<0.0001). At the time of the final rPFS analysis, overall survival (OS) data were not yet mature. The safety profile of Xtandi in this study was consistent with that observed in studies of castration-resistant prostate cancer (CRPC). The incidence of Grade 3–4 adverse events was 23.6% in the Xtandi plus ADT arm and 24.7% in the placebo plus ADT arm. No unexpected adverse events were reported.

Currently, the new indication application for Xtandi in the treatment of mHSPC is also under review by regulatory authorities in the European Union and Japan. The applications in these countries and regions are based on data from two Phase III clinical studies, ARCHES and ENZAMET. The ENZAMET study enrolled a total of 1,125 patients with mHSPC and met its primary endpoint: compared with the standard non-steroidal anti-androgen (NSAA; bicalutamide, nilutamide, or flutamide) plus ADT regimen, the Xtandi plus ADT regimen significantly reduced the risk of death by 33% (HR=0.67 [95% CI: 0.52–0.86]; p=0.002). The 3-year overall survival (OS) rate was 80% in the Xtandi plus ADT group, compared with 72% in the NSAA plus ADT group. Adverse events during the follow-up period were consistent with known safety profiles related to disease stage, patient age, and study protocols. The incidence of seizures and fatigue was higher in the Xtandi plus ADT group, as was the rate of treatment discontinuation due to adverse events.

Globally, prostate cancer is the second leading cause of cancer-related death in men, after lung cancer. Prostate cancer typically occurs in older men and is often driven by excessive levels of male hormones, including testosterone (an androgen). The standard clinical approach to treatment involves reducing androgen levels in the body, which can be achieved through surgical castration and/or androgen deprivation therapy (ADT). Metastatic prostate cancer refers to cases where cancer cells have spread beyond the prostate to other parts of the body, such as the bones, lymph nodes, bladder, and rectum. If patients at this stage still respond to treatments that lower testosterone levels—whether through surgery or medication—the disease is considered hormone-sensitive (or castration-sensitive). It is estimated that in 2019, more than 40,000 new cases of metastatic hormone-sensitive prostate cancer (mHSPC) will be diagnosed in the United States.

Xtandi (Ankotan, enzalutamide), co-developed and co-marketed by Astellas and Pfizer, is an androgen receptor signaling inhibitor administered orally once daily. Xtandi directly targets the androgen receptor (AR) and acts at three steps in the AR signaling pathway: (1) inhibition of androgen binding—where androgen binding induces conformational changes that trigger receptor activation; (2) prevention of nuclear translocation—the translocation of AR into the nucleus is an essential step in AR-mediated gene regulation; and (3) impairment of DNA binding—the binding of AR to DNA is critical for regulating gene expression.

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.

Xtandi is the world’s best-selling prostate cancer drug, with sales reaching $3.6 billion in 2018. As part of their clinical development program in prostate cancer, Pfizer and Astellas are currently conducting another Phase III clinical study, EMBARK (ClinicalTrials.gov identifier: NCT02319837), to evaluate the therapeutic potential of Xtandi plus leuprolide combination therapy and Xtandi monotherapy versus leuprolide monotherapy in men with high-risk non-metastatic hormone-sensitive prostate cancer (HSPC). (Bioon.com)

Original Source:XTANDI® (ENZALUTAMIDE) APPROVED BY U.S. FDA FOR THE TREATMENT OF METASTATIC CASTRATION-SENSITIVE PROSTATE CANCER