Bayer Submits Darolutamide for Marketing Authorization in Japan for Non-Metastatic Castration-Resistant Prostate Cancer

March 06, 2019/Bio ValleyBIOON/--German pharmaceutical giantBayer(Bayer) recently announced that it has submitted a marketing authorization application to the Japanese Ministry of Health, Labour and Welfare (MHLW) for darolutamide for the treatment of patients with castration-resistant prostate cancer (CRPC). This submission is based on data from the pivotal Phase III ARAMIS clinical trial of darolutamide in non-metastatic castration-resistant prostate cancer (nmCRPC). The results demonstrated that, in patients with nmCRPC, the darolutamide plus androgen deprivation therapy (ADT) regimen significantly reduced the risk of metastasis or death by 59% compared with placebo plus ADT. The study also showed that the darolutamide plus ADT regimen had a favorable safety profile compared with placebo plus ADT.

Recently, Bayer has completed the rolling submission of a new drug application to the U.S. FDA for darolutamide in the treatment of nmCRPC. In the United States,FDADarolutamide had previously been granted Fast Track designation for the treatment of nmCRPC. Bayer is also in discussions with regulatory authorities in other countries regarding the submission of applications for darolutamide. Darolutamide was developed by Bayer in collaboration with Orion, a Finnish pharmaceutical company. In addition to nmCRPC, the two companies are advancing another Phase III clinical study, ARASENS, to evaluate the efficacy and safety of darolutamide in treating metastatic hormone-sensitive prostate cancer (mHSPC).

Darolutamide is an oral nonsteroidal androgen receptor antagonist with a unique chemical structure, exhibiting strong binding affinity to the receptor and potent antagonistic activity, thereby inhibiting receptor function and the growth of prostate cancer cells.

Senior Vice President of Bayer Pharmaceuticals Division andTumorScott Z. Fields, Head of Development, stated, “In the early stages of prostate cancer, patients are typically asymptomatic. Therefore, it is crucial to provide patients with treatment options that significantly delay metastatic progression while limiting treatment-related side effects, enabling them to maintain their daily lives. With this submission, we are one step closer to delivering a potential new therapeutic option for CRPC to patients and physicians in Japan.”

Molecular structure of darolutamide (Image source: Wikipedia)

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 but were at high risk for metastatic disease. In the study, patients were randomized in a 2:1 ratio to two groups, receiving 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 study results showed that, compared with the placebo + ADT regimen group, the darolutamide + ADT regimen 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 disease 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 treatment groups; only fatigue occurred in more than 10% of patients (12.1% in the darolutamide + ADT group vs. 8.7% in the placebo + ADT group), and quality-of-life outcomes were similar between the two treatment groups.

These data were presented in mid-February this year at the American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium held in San Francisco, USA.Tumorpresented at the ASCO GU symposium and simultaneously published in The New England Journal of Medicine (NEJM). (Bioon.com)

Original Source:Bayer submits darolutamide for marketing authorization in Japan