Darolutamide receives approval for additional prostate cancer indication in Japan

• Darolutamide approved for metastatic prostate cancer as well as non-metastatic castration-resistant prostate cancer  
• New approval is based on data from the pivotal Phase III ARASENS trial

The Ministry of Health, Labor and Welfare (MHLW) in Japan has approved the oral androgen receptor inhibitor (ARi) darolutamide plus ADT in combination with docetaxel in the indication of metastatic prostate cancer. The MHLW approval is based on the positive results from the Phase III ARASENS trial, which demonstrated that darolutamide plus androgen deprivation therapy (ADT) in combination with docetaxel significantly reduced the risk of death by 32.5% compared to ADT with docetaxel, in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Additionally, the darolutamide combination showed consistent benefits across clinically relevant secondary endpoints, with the overall incidence of treatment-emergent adverse events being similar between treatment arms. These results were published in The New England Journal of Medicine.¹

Darolutamide is already approved in Japan for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) under the brand name Nubeqa®.

Darolutamide plus ADT in combination with docetaxel was recently recommended for EU marketing authorisation for the treatment of mHSPC by the European Medicine Agency’s Committee for Medicinal Products for Human Use (CHMP), with a final decision expected in the coming months. The compound is already approved in its second indication, mHSPC, in a number of markets including the U.S. Filings in other regions are underway or planned by Orion’s collaboration partner Bayer.

Darolutamide is being investigated in a broad development program with three additional ongoing or planned large clinical studies, to evauate its potential across prostate cancer patients from the early- to the late-stage of this disease. This includes the ARANOTE Phase III trial evaluating darolutamide plus androgen deprivation therapy (ADT) versus ADT alone for mHSPC.

Darolutamide is developed jointly by Orion and Bayer.

About the ARASENS Trial

The ARASENS trial is a randomized, Phase III, multi-center, double-blind, placebo-controlled trial which was prospectively designed to investigate the efficacy and safety of oral darolutamide, an androgen receptor inhibitor (ARi), plus androgen deprivation therapy (ADT) and the chemotherapy docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC). A total of 1,306 newly diagnosed patients were randomized in a 1:1 ratio to receive 600 mg of darolutamide twice a day or matching placebo, plus ADT and docetaxel.

The primary endpoint of this trial was overall survival (OS). Secondary endpoints included time to castration-resistant prostate cancer (CRPC), time to pain progression, time to first symptomatic skeletal event (SSE), time to initiation of subsequent anticancer therapy, all measured at 12‐week intervals, as well as adverse events (AEs) as a measure of safety and tolerability. Results from this trial were published in the New England Journal of Medicine.¹ A plain language summary publication of these data was published in Future Oncology.² The ARASENS trial demonstrated that darolutamide plus androgen deprivation therapy (ADT) and docetaxel significantly reduced the risk of death by 32.5% compared to ADT plus docetaxel.¹ Improvements in the secondary endpoints supported the benefit observed in the primary endpoint, overall survival.¹

About Metastatic Hormone-Sensitive Prostate Cancer

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

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. Upon relapse, when the disease will metastasise or spread, or if the disease is newly diagnosed, but has already spread, the disease is hormone-sensitive and androgen deprivation therapy (ADT) is the cornerstone of treatment for this hormone-sensitive disease. Current treatment options for men with metastatic hormone-sensitive prostate cancer (mHSPC) include hormone therapy, such as ADT, androgen receptor pathway inhibitors plus ADT or a combination of docetaxel chemotherapy and ADT. Despite these treatments, a large proportion of men with mHSPC will eventually experience progression to metastatic castration-resistant prostate cancer (mCRPC), a condition with limited survival.

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 trial⁴ and the maintained verbal learning and memory observed in the darolutamide arm of the Phase II ODENZA trial.⁵

The product is approved under the brand name Nubeqa® in more than 80 countries around the world, including the U.S., EU, Japan and China, 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. Filings in other regions are underway or planned by Bayer. 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. Information about these trials can be found at www.clinicaltrials.gov. In addition, a study to explore the potential of darolutamide in the early setting for patients who have experienced a rise in their prostate specific antigen (PSA) levels following surgery or radiation, is also planned.