Bayer Announces Japanese Approval of Nubeqa (darolutamide) for Non-Metastatic Castration-Resistant Prostate Cancer

January 26, 2020 /BioValleyBIOON/ -- German pharmaceutical giantBayer(Bayer) recently announced that the Japanese Ministry of Health, Labour and Welfare (MHLW) has approved Nubeqa (darolutamide) for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC) in men, namelyTumorProstate cancer patients whose disease has not yet metastasized to other parts of the body and who no longer respond to medical or surgical therapies aimed at lowering testosterone levels. This drug will provide clinicians in Japan with a new treatment option that can significantly prolong metastasis-free survival (MFS) in the management of patients with nmCRPC.

Nubeqa is an oral non-steroidal androgen receptor (AR) inhibitor developed by Bayer in collaboration with the Finnish pharmaceutical company Orion. The drug has been approved in the United States and Brazil, with applications underway or planned in the European Union and other regions.

This approval is based on data from the pivotal Phase III ARAMIS study. The results demonstrated that, in patients with non-metastatic castration-resistant prostate cancer (nmCRPC), darolutamide plus androgen deprivation therapy (ADT) significantly prolonged metastasis-free survival (median MFS: 40.4 months vs. 18.4 months; p<0.0001) and reduced the risk of metastasis or death by 59% (HR=0.41; 95% CI: 0.34–0.50) compared with placebo plus ADT. The darolutamide plus ADT regimen exhibited a favorable safety profile in this study.

Globally, prostate cancer is the second most common malignancy in menTumor, in 2018, an estimated 1.2 million people were diagnosed with prostate cancer, and 358,000 died from the disease. Prostate cancer is the fifth leading cause of cancer-related deaths among men, primarily affecting men over the age of 50, with the risk increasing as they age.Castration-Resistant Prostate Cancer (CRPC) refers to prostate cancer that continues to progress despite androgen deprivation therapy (ADT) reducing testosterone levels in the body to very low levels. Approximately one-third of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) develop metastases within two years. Patients with nmCRPC are typically asymptomatic, and the primary treatment goal is to delay the spread of prostate cancer while limiting treatment-related side effects.

ARAMIS was a randomized, multicenter, double-blind, placebo-controlled study that enrolled 1,509 patients who were receiving androgen deprivation therapy (ADT) as standard of care and were at high risk for metastatic disease. In the study, patients were randomized in a 2:1 ratio to receive either darolutamide (600 mg twice daily) or placebo, in addition to ADT. The primary endpoint was metastasis-free survival (MFS), defined as the time from randomization to evidence of metastasis or death. Secondary endpoints included overall survival (OS), time to pain progression, time to initiation of first cytotoxic chemotherapy, time to first symptomatic skeletal event (SSE), and the safety and tolerability profile of darolutamide.

The results showed that, compared with the placebo + ADT group, the darolutamide + ADT group achieved a statistically significant improvement in MFS (HR = 0.41, 95% CI: 0.34–0.50, p < 0.001), indicating a 59% reduction in the risk of metastasis or death, thereby meeting the primary endpoint of the study. The median MFS was 18.4 months in the placebo + ADT group and 40.4 months in the darolutamide + ADT group, representing an overall extension of median MFS by 22 months.

In terms of overall survival (OS), the darolutamide + ADT regimen demonstrated a favorable trend compared with the placebo + ADT regimen, with a 29% reduction in the risk of death (HR=0.71, 95% CI: 0.50–0.99, p=0.045). Regarding progression-free survival (PFS), the darolutamide + ADT regimen significantly prolonged PFS compared with the placebo + ADT regimen (median PFS: 36.8 months vs. 14.8 months; HR=0.38, 95% CI: 0.32–0.45, p<0.001), reducing the risk of local progression, distant metastasis, or death by 62%.

Furthermore, all other secondary endpoints favored darolutamide, including time to pain progression (40.3 months vs. 25.4 months; HR=0.65, 95% CI: 0.53–0.79, p<0.001) and time to cytotoxic chemotherapy (not reached vs. 38.2 months; HR=0.43, 95% CI: 0.31–0.60, p<0.001). Another secondary endpoint, time to first symptomatic skeletal event (SSE), also favored darolutamide. Importantly, the incidence of treatment-emergent adverse events (AEs) occurring in ≥5% of patients or classified as grade 3–5 was comparable between the two groups; only fatigue occurred in more than 10% of patients (12.1% in the darolutamide group vs. 8.7% in the placebo group), and quality-of-life outcomes were similar between the two groups. (Bioon.com)

Original Source:Bayer receives approval for darolutamide in Japan