On July 17, 2024 Orion reported that the Phase III ARANOTE trial, investigating darolutamide plus ADT in patients with metastatic hormone-sensitive prostate cancer (mHSPC), has met its primary endpoint of rPFS (Press release, Orion, JUL 17, 2024, View Source [SID1234644909]). Darolutamide plus ADT significantly increased rPFS compared to placebo plus ADT. The safety data were comparable between both treatment arms and reconfirm the established tolerability profile of darolutamide in advanced prostate cancer.

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

                  Schedule Your 30 min Free Demo!

Darolutamide is already approved 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, and patients with metastatic hormone-sensitive prostate cancer (mHSPC, in combination with ADT and docetaxel).

"The results of the ARANOTE trial reconfirm that darolutamide, a compound discovered by Orion scientists, is a viable treatment option for patients with metastatic hormone-sensitive prostate cancer. In these patients, darolutamide has now shown efficacy with and without docetaxel, and thus, pending regulatory approval, can provide choices for the personalised treatment regime. I would like to thank all the patients and the investigators who participated in the ARANOTE trial," said Professor, M.D., Ph.D. Outi Vaarala, Senior Vice President of Innovative Medicines and Research & Development at Orion.

Detailed results of the ARANOTE trial are planned to be presented at a forthcoming scientific congress. Bayer plans to submit the data from the study to relevant global health authorities to support expanded use of darolutamide in men with mHSPC.

ARANOTE is part of a robust clinical development program investigating darolutamide across various stages of prostate cancer, which includes the Phase III ARASTEP trial evaluating darolutamide plus ADT versus ADT alone in hormone-sensitive high-risk biochemical recurrence (BCR) prostate cancer, who have no evidence of metastatic disease by conventional imaging and a positive PSMA PET/CT at baseline. Furthermore, darolutamide is also being investigated by Bayer in the collaborative Phase III DASL-HiCaP (ANZUP1801) trial led by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP). The study evaluates darolutamide as an adjuvant treatment for localized prostate cancer with very high risk of recurrence.

About the ARANOTE trial
The ARANOTE trial is a randomized, double-blind, placebo-controlled Phase III study designed to assess the efficacy and safety of darolutamide plus ADT in patients with mHSPC. A total of 669 patients were randomized to receive 600mg of darolutamide twice daily or matching placebo in addition to ADT.

The primary endpoint of this study is rPFS, measured as time from randomization to date of first documented radiological progressive disease or death due to any cause, whichever occurs first. Secondary endpoints include overall survival (time to death from any cause), time to first castration-resistant event, time to initiation of subsequent anti-cancer therapy, time to prostate-specific antigen (PSA) progression, PSA undetectable rates, time to pain progression, and safety assessments.

About metastatic hormone-sensitive prostate cancer
Prostate cancer is the second most common cancer in men and the fifth most common cause of cancer death in men worldwide.1 In 2020, an estimated 1.4 million men were diagnosed with prostate cancer, and about 375,000 died from the disease worldwide.2

At the time of diagnosis, most men have localized prostate cancer, meaning their cancer is confined to the prostate gland and can be treated with curative surgery or radiotherapy. mHSPC is a stage in the disease where the cancer has spread outside of the prostate to other parts of the body. Up to 10% of men will already present with mHSPC when first diagnosed.3, 4, 5 For patients with mHSPC, ADT is the cornerstone of treatment, often in combination with chemotherapy docetaxel and/or an androgen receptor inhibitor (ARi). Despite treatment, most men with mHSPC will eventually progress to castration-resistant prostate cancer (CRPC), a condition with limited survival.

About darolutamide
Darolutamide is an oral ARi with a distinct chemical structure that binds to the androgen 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. This is also supported by 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 the maintained verbal learning and memory observed in the darolutamide arm of the Phase II ODENZA trial.

Darolutamide is approved under the brand name Nubeqa in more than 85 countries 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. It is also approved in combination with ADT and docetaxel for the treatment of patients with mHSPC in over 80 markets including the U.S., Japan, EU, and China. The product is developed jointly by Orion and Bayer.