Orion and Bayer expand clinical development program for darolutamide in prostate cancer

• 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

About darolutamide

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.