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Inside information: Phase III ARANOTE trial of darolutamide in combination with androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer meets primary endpoint

ORION CORPORATION
STOCK EXCHANGE RELEASE – INSIDE INFORMATION
17 JULY 2024 at 8.30 EEST     

        
Inside information: Phase III ARANOTE trial of darolutamide in combination with androgen deprivation therapy in men with metastatic hormone-sensitive prostate cancer meets primary endpoint

• Orion and Bayer’s Phase III ARANOTE trial meets primary endpoint, significantly increasing radiological progression-free survival (rPFS) with darolutamide + androgen deprivation therapy (ADT) compared to placebo plus ADT.
• Safety analysis shows darolutamide plus ADT to be comparable to placebo plus ADT, reconfirming the established tolerability profile of darolutamide as observed in the ARAMIS and ARASENS trials.
• Darolutamide plus ADT now has positive data both with and without docetaxel based on two pivotal phase III studies in metastatic hormone-sensitive prostate cancer (mHSPC).
  
  
• Bayer plans to present the pivotal data at a forthcoming scientific congress and prepare for submission with health authorities globally to extend the indication of darolutamide.
  
  

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. 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.

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.

Orion Corporation

Liisa Hurme President and CEO

Outi Vaarala SVP, Innovative Medicines and Research & Development

                                                
Contact person:
Outi Vaarala, SVP, Innovative Medicines and Research & Development, Orion Corporation
Tel. +358 10 426 3472
outi.vaarala@orionpharma.com

Reference

1. Sung H et al. Ca Cancer J Clin 2021; 71:209–249.
2. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians. https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.3322/caac.21660 Accessed: June 2024.
3. Piombino C et al. Cancers (Basel). 2023 Oct 11;15(20):4945.
4. Helgstrand JT et al. Cancer. 2018;124(14):2931-2938.
5. Buzzoni C et al. Eur. Urol. 2015;68:885–890.
   
   

Publisher:
Orion Corporation
Communications
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Orion is a globally operating Finnish pharmaceutical company – a builder of well-being for over a hundred years. We develop, manufacture and market human and veterinary pharmaceuticals and active pharmaceutical ingredients. Orion has an extensive portfolio of proprietary and generic medicines and consumer health products. The core therapy areas of our pharmaceutical R&D are oncology and pain. Proprietary products developed by Orion are used to treat cancer, neurological diseases and respiratory diseases, among others. Orion's net sales in 2023 amounted to EUR 1,190 million and the company had about 3,600 employees at the end of the year. Orion's A and B shares are listed on Nasdaq Helsinki.