Clinical Trial Update

Bayer And Orions Nubeqa Phase III ARASENS Trial In Metastatic Hormone-sensitive Prostate Cancer Meets Primary Endpoint

December 06,2021 11:04 AM
- By Admin

The phase III ARASENS trial investigating the use of the oral androgen receptor inhibitor (ARi) Nubeqa (darolutamide) in metastatic hormone-sensitive prostate cancer (mHSPC) has met its primary endpoint.

In the ARASENS trial, darolutamide in combination with docetaxel and androgen deprivation therapy (ADT) significantly increased overall survival (OS) compared to docetaxel and ADT. The overall incidence of reported adverse events was similar between treatment arms. Detailed results of the study are planned to be presented at an upcoming scientific congress.

The ARASENS trial is the only phase III randomized, multi-center, double-blind trial which was prospectively designed to evaluate the efficacy and safety of a combination of an ARi with docetaxel and ADT compared to docetaxel and ADT in patients with mHSPC.

Darolutamide is approved in multiple markets around the world, including the US, the European Union, Japan and China, under the brand name Nubeqa, for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease. Filings in other regions are underway or planned. The product is developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company.

“For patients with mHSPC, there remains a significant need for new therapeutic approaches that improve treatment outcomes. ARASENS was prospectively designed to investigate whether combining darolutamide with docetaxel and ADT could lead to an increase in overall survival for men with mHSPC,” said Scott Z. Fields, senior vice president and head of oncology development at Bayer's Pharmaceutical Division. “We are especially grateful to the patients and investigators for participating in this important trial and look forward to presenting the full results at an upcoming meeting.”

Bayer plans to discuss the data from ARASENS trial with health authorities worldwide regarding the submission for marketing authorization in this indication.

The ARASENS trial is a randomized, phase III, multi-center, double-blind, placebo-controlled trial which was prospectively designed to investigate the safety and efficacy of oral darolutamide, an androgen receptor inhibitor (ARi), in combination with the chemotherapy docetaxel and androgen deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). 1,306 newly diagnosed patients were randomized in a 1:1 ratio to receive 600 mg of darolutamide twice a day or matching placebo, in addition to docetaxel and standard ADT.

The primary endpoint of this trial is overall survival (OS). Secondary endpoints include time to castration-resistant prostate cancer (CRPC), time to initiation of subsequent anticancer therapy, time to first symptomatic skeletal event (SSE), time to pain progression, all measured at 12-week intervals, as well as adverse events as a measure of safety and tolerability.

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.

Darolutamide is an oral androgen receptor inhibitor (ARi) with a distinct chemical structure that binds to the receptor with high affinity and exhibits strong antagonistic activity, thereby inhibiting the receptor function and the growth of prostate cancer cells. The low potential for blood-brain barrier penetration for darolutamide is supported by preclinical models and neuroimaging data in healthy humans. A low blood-brain barrier penetration would explain the overall low incidence of central nervous system (CNS)-related adverse events (AEs) compared to placebo as seen in the ARAMIS phase III trial and significant improvement in verbal memory in the phase II ODENZA trial. The product is approved under the brand name Nubeqa in several markets around the world for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease. The compound is also being investigated in further studies across various stages of prostate cancer, including another Phase III trial in metastatic hormone-sensitive prostate cancer (mHSPC) (ARANOTE) as well as a Phase III trial evaluating darolutamide as an adjuvant treatment for localized prostate cancer with very high risk of recurrence (DASL-HiCaP).