Bayer has announced regulatory submissions in Japan and China seeking approval for darolutamide, an oral androgen receptor inhibitor (ARi), for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). The applications to the Ministry of Health, Labor and Welfare (MHLW) in Japan and the Center of Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) request authorization for darolutamide in combination with docetaxel and androgen deprivation therapy (ADT). These submissions are based on the pivotal Phase III ARASENS trial results, which demonstrated a statistically significant improvement in overall survival for patients with mHSPC.
The ARASENS trial, a randomized, Phase III, multi-center, double-blind study, compared darolutamide plus ADT and docetaxel to ADT plus docetaxel in 1,306 newly diagnosed mHSPC patients. The primary endpoint, overall survival (OS), showed a statistically significant benefit for the darolutamide arm. Secondary endpoints included time to castration-resistant prostate cancer (CRPC), time to pain progression, and time to first symptomatic skeletal event (SSE).
"Prostate cancer is the most common new cancer diagnosis in Japanese men annually," said Christine Roth, Member of the Executive Committee of Bayer’s Pharmaceutical Division and Head of the Oncology Strategic Business Unit at Bayer. "The submission to the MHLW for darolutamide in this new indication is an important next step in Bayer’s commitment to bring forward a potential new therapy for eligible patients with mHSPC to extend lives and delay disease progression, while providing a promising safety profile."
In China, the incidence and mortality rates of prostate cancer are increasing, with nearly a third of newly diagnosed patients presenting with metastatic disease. Roth noted, "There is therefore a significant need for treatment options that extend overall survival and delay disease progression. Bringing forward this potential new treatment option with high efficacy and a favorable safety profile to more appropriate patients around the world, is part of Bayer’s broader commitment to improve outcomes for men living with prostate cancer."
Darolutamide, marketed under the brand name Nubeqa™, is already approved in over 60 markets, including the U.S., the European Union (EU), Japan, and China, for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) who are at high risk of developing metastatic disease. Darolutamide is characterized by its distinct chemical structure, high-affinity binding to the androgen receptor, and strong antagonistic activity, inhibiting receptor function and prostate cancer cell growth. Preclinical and neuroimaging data suggest a low potential for blood-brain barrier penetration, potentially contributing to a low incidence of central nervous system (CNS)-related adverse events.
Bayer and Orion Corporation, a Finnish pharmaceutical company, jointly develop darolutamide. Bayer is also investigating darolutamide in other studies across various stages of prostate cancer, including another Phase III trial in mHSPC (ARANOTE) and an ANZUP-led international co-operative group Phase III trial evaluating darolutamide as an adjuvant treatment for localized prostate cancer with a very high risk of recurrence (DASL-HiCaP, ANZUP1801).
Prostate cancer is the second most commonly diagnosed malignancy in men worldwide. In 2020, an estimated 1.4 million men were diagnosed with prostate cancer, and about 375,000 died from the disease worldwide. Current treatment options for mHSPC include hormone therapy, androgen receptor pathway inhibitors plus ADT, or a combination of docetaxel and ADT. However, a significant proportion of men with mHSPC eventually progress to metastatic castration-resistant prostate cancer (mCRPC), a condition associated with limited survival.
