ORION CORPORATION
PRESS RELEASE
16 SEPTEMBER 2024 at 11.30 EEST

        
Darolutamide plus androgen deprivation therapy significantly reduced the risk of radiological progression or death by 46% compared to placebo plus ADT in patients with metastatic hormone-sensitive prostate cancer

• Results from the pivotal Phase III ARANOTE trial evaluating darolutamide plus androgen deprivation therapy (ADT) showed a statistically significant increase in radiological progression-free survival (rPFS) compared to placebo plus ADT in patients with metastatic hormone-sensitive prostate cancer
• 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
• Safety analysis reconfirms the established tolerability profile of darolutamide as observed in the ARAMIS and ARASENS trials
• Data from ARANOTE trial presented as a late-breaking oral presentation at the ESMO 2024 Congress and simultaneously published in The Journal of Clinical Oncology

Abstract: LBA68

Results from the Phase III ARANOTE trial have shown that darolutamide plus androgen deprivation therapy (ADT) significantly reduced the risk of radiological progression or death by 46% compared to placebo plus ADT (HR 0.54; 95% CI 0.41–0.71; P<0.0001), in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Consistent benefits in rPFS were observed across prespecified subgroups, including patients with high- and low-volume mHSPC. Treatment emergent adverse event (TEAEs) were low and similar between treatment groups. The results were presented at the 2024 ESMO Congress and have been simultaneously published in The Journal of Clinical Oncology.

“Darolutamide, a compound originated by Orion R&D, continues to deliver clinical benefit in patients with metastatic hormone-sensitive prostate cancer, now in ARANOTE with ADT alone and earlier in ARASENS in combination with ADT and docetaxel. These results also reflect our fruitful collaboration with Bayer for more than ten years with a focus to deliver new personalised treatment options to the patients with prostate cancer,” said Professor, M.D., Ph.D. Outi Vaarala, Senior Vice President of Innovative Medicines and Research & Development at Orion.

Bayer plans to submit the data from the ARANOTE trial to health authorities globally to support the expanded use of darolutamide in patients with mHSPC. Darolutamide is already approved for the treatment of patients with mHSPC under the brand name Nubeqa® in combination with ADT and docetaxel in more than 80 markets, and for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease, in over 85 countries around the world. The product is developed jointly by Orion and Bayer.

Detailed results from ARANOTE
Darolutamide plus ADT significantly reduced the risk of radiological progression or death by 46% (HR 0.54; 95% CI 0.41–0.71; P<0.0001), compared with placebo plus ADT. Consistent benefits in rPFS were observed across patient subgroups, including high- and low-volume mHSPC, with a risk reduction by 40% and 70% (HR 0.60; 95% CI 0.44-0.80 and HR 0.30; 95% CI 0.15-0.50) respectively. An analysis of immature data of overall survival (OS), which measures the time from treatment until death from any cause, was suggestive of a potential benefit with darolutamide plus ADT (HR=0.81, 95% CI 0.59-1.12) vs placebo plus ADT. The ARANOTE data also suggested numerical clinical benefits across all other secondary endpoints including delaying the time to CRPC (HR 0.40; 95% CI, 0.32–0.51), time to PSA progression (HR 0.31; 95% CI 0.23–0.41), time to pain progression (HR 0.72; 95% CI, 0.54–0.96), and time to initiation of subsequent systemic therapy (HR 0.40; 95% CI, 0.29–0.56), compared to placebo plus ADT.

Incidences of treatment-emergent adverse events (TEAEs) were low (most were grade 1 or 2) and similar between treatment arms, and treatment discontinuations due to TEAEs were lower in patients receiving darolutamide compared to placebo plus ADT (6.1% vs 9.0%). The most frequently reported AEs (incidence of ≥10%) for darolutamide plus ADT vs placebo, were anemia (20.4% and 17.6%, respectively), arthralgia (12.4% and 11.3%, respectively), and urinary tract infections (11.7% and 7.7%, respectively). The incidence of fatigue was lower with darolutamide plus ADT vs placebo (5.6% and 8.1%, respectively). Incidence of TEAEs of interest were minimal between treatment arms, with a difference of ≤2% for coronary artery disorders, cardiac arrhythmias, and vasodilation/flushing.

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. 669 patients were randomized 2:1 to receive either 600mg of darolutamide twice daily or 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 darolutamide
Darolutamide is an oral androgen receptor inhibitor (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.

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 compared to 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 scan 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 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 2022, an estimated 1.5 million men were diagnosed with prostate cancer, and about 397,000 died from the disease worldwide.¹ Prostate cancer diagnoses are projected to increase from 1.4 million annually in 2020 to 2.9 million by 2040.²     

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 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 metastatic castration-resistant prostate cancer (mCRPC), a condition with limited survival.

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

References

1. Bray F et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.21834 Accessed: August 2024.
2. James ND et al. Lancet 2024; 403: 1683–722.
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.