- Phase III study ARASTEP initiated in hormone-sensitive prostate cancer, in patients with high-risk biochemical recurrence (BCR) who have no evidence of metastatic disease by conventional imaging and a positive PSMA PET/CT at baseline
- Fifth major clinical trial for androgen receptor inhibitor (ARi) darolutamide, covering prostate cancer from early to metastatic stage
Orion and Bayer further expand the global clinical development program for the oral androgen receptor inhibitor (ARi) darolutamide in prostate cancer. The new Phase III clinical study, ARASTEP, will investigate the efficacy of darolutamide plus androgen deprivation therapy (ADT) versus ADT alone in hormone-sensitive prostate cancer, in patients with high-risk biochemical recurrence (BCR) who have no evidence of metastatic disease by conventional imaging and a positive PSMA PET/CT at baseline. BCR is defined as rising prostate-specific antigen (PSA) levels with a doubling time of <12 months1 after primary treatment (surgery or radiotherapy)2. 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 as well as metastatic hormone-sensitive prostate cancer (mHSPC).
“Darolutamide has already shown its beneficial treatment effects in two patient groups: patients with non-metastatic castration-resistant prostate cancer who are at high risk of developing metastatic disease as well as in patients with metastatic hormone-sensitive prostate cancer in combination with chemotherapy. As a natural continuum we want to assess the potential of darolutamide in the earlier stage of disease, and further expand the patient population that can benefit from darolutamide,” said Professor, M.D., Ph.D. Outi Vaarala, Senior Vice President of Innovative Medicines and Research and Development at Orion.
The compound is also being investigated in further studies across various stages of prostate cancer, including in the ARANOTE Phase III trial evaluating darolutamide plus androgen deprivation therapy (ADT) versus ADT alone for metastatic hormone-sensitive prostate cancer (mHSPC), as well as the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) led international Phase III co-operative group DASL-HiCaP (ANZUP1801) trial evaluating darolutamide as an adjuvant treatment for localised prostate cancer with very high risk of recurrence.
Darolutamide is jointly developed by Orion and Bayer.
About the ARASTEP trial
The ARASTEP trial is a randomized, double-blind, placebo-controlled Phase III study of darolutamide plus androgen deprivation therapy (ADT) versus placebo plus ADT in hormone-sensitive prostate cancer, in patients with high-risk biochemical recurrence (BCR) who have no evidence of metastatic disease by conventional imaging and a positive PSMA PET/CT at baseline. The primary endpoint of this study is radiological progression-free survival (rPFS), measured by PSMA PET/CT assessed by independent central review. The trial is expected to enroll approximately 750 participants. Patients will be randomized to receive the standard regimen of 600mg of darolutamide twice a day or matching placebo, plus ADT.
About hormone-sensitive prostate cancer and biochemical recurrence (BCR)
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.3
Hormone-sensitive prostate cancer is a type of prostate cancer that needs androgens (male hormones) to grow and therefore stops growing when androgens are not present. Almost all early-stage prostate cancers are androgen-dependent.4
Up to 50% of patients with prostate cancer develop elevated prostate-specific antigen (PSA) levels in their blood after primary therapy (surgery and/or radiation therapy).5 This disease state is called biochemical recurrence (BCR). Current treatment options for patients with biochemical recurrent prostate cancer include prostatectomy, intending to be curative. If these treatments are unsuccessful, androgen deprivation therapy (ADT) is an option to control disease.2
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. This is 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 trial6 and the maintained verbal learning and memory observed in the darolutamide arm of the Phase II ODENZA trial.7
The product is approved under the brand name Nubeqa® in more than 80 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 for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC) in a number of markets including the U.S., Japan, EU and China. Filings in other regions are underway or planned by Bayer.
Tuukka Hirvonen, Investor Relations
tel. +358 10 426 2721
- Simon NI, Parker C, Hope TA, Paller CJ, Best Approaches and Updates for Prostate Cancer Biochemical Recurrence. Am Soc Clin Oncol Educ Book. 2022 Apr;42: 1–8.
- Fakhrejahani, F., Madan, R.A. & Dahut, W.L. Management Options for Biochemically Recurrent Prostate Cancer. Curr. Treat. Options in Oncol. 2017;18 (26).
- 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 March 2023.
- National Cancer Institute. NCI Dictionary of Cancer Terms. Hormone-sensitive prostate cancer. https://www.cancer.gov/publications/dictionaries/cancer-terms/def/hormone-sensitive-prostate-cancer. Accessed March 2023.
- Lin X, Kapoor A, Gu Y, Chow MJ, Xu H, Major P, et al. Assessment of biochemical recurrence of prostate cancer (Review). Int J Oncol. 2019 Dec;55(6):1194-212.
- Fizazi, K et al. Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer. N Engl J Med. 2019; 380:1235–1246.
- Colomba E. et al. ODENZA: A French prospective, randomized, open-label, multicenter, cross-over phase II trial of preference between darolutamide and enzalutamide in men with asymptomatic or mildly symptomatic metastatic castrate-resistant prostate cancer (CRPC). J Clin Onc 2021; 39 (15_suppl): 5046-5046.
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Orion is a globally operating Finnish pharmaceutical company – a builder of well-being. We develop, manufacture and market human and veterinary pharmaceuticals and active pharmaceutical ingredients. Orion has an extensive portfolio of proprietary and generic medicines and self-care 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 2022 amounted to EUR 1,341 million and the company had about 3,500 employees at the end of the year. Orion's A and B shares are listed on Nasdaq Helsinki.