Orion Corporation. (1/23/20). "Press Release: Marketing Authorization Granted for Darolutamide in Japan".

	Region	Japan
	Organisation	Bayer Pharma AG
	Group	Bayer (Group)
	Product	Nubeqa®
	Product 2	phase 3 study

The Japanese Ministry of Health, Labor and Welfare (MHLW) has granted marketing authorization for darolutamide, under the brand name Nubeqa®, for the treatment of men with non-metastatic castration-resistant prostate cancer (nmCRPC).

The approval is based on the Phase III ARAMIS trial evaluating the efficacy and safety of darolutamide plus androgen deprivation therapy (ADT) compared to placebo plus ADT, showing a highly significant improvement in the primary efficacy endpoint of metastasis-free survival (MFS), with a median 40.4 months for darolutamide plus ADT versus 18.4 months for placebo plus ADT (HR=0.41, 95% CI 0.34-0.50; P<0.001). The androgen receptor inhibitor (ARi), which is jointly developed by Orion and Bayer is already approved in the U.S. and Brazil and filings in the European Union and other regions are underway or planned by Bayer.

“Patients with nmCRPC are usually asymptomatic, but have a rising blood prostate specific antigen (PSA) despite ADT treatment, and it is important to prevent their cancer from becoming metastatic and symptomatic. The overarching goals of treatment in this setting are to delay the spread of prostate cancer and limit the burdensome side effects of therapy. Darolutamide provides nmCRPC patients now also in Japan a new therapeutic option that addresses these questions” said Christer Nordstedt, Senior Vice President, Research and Development, Orion Corporation.

In Japan, over 89,000 men are estimated to be diagnosed with prostate cancer annually, making it the second most-common cancer diagnosis in Japanese men after stomach cancer. Prostate cancer that is treated with ADT but keeps progressing even when the amount of testosterone is reduced to very low levels in the body is known as castration-resistant prostate cancer (CRPC).1 In men with progressive nmCRPC, a rapid prostate specific antigen (PSA) doubling time has been consistently associated with reduced time to first metastasis and death.1

In the ARAMIS trial, overall survival (OS) and time to pain progression were additional secondary efficacy endpoints. At the time of final MFS analysis, a positive trend in OS was observed; OS data were not yet mature. The MFS result was additionally supported by a delay in time to pain progression as compared to placebo plus ADT. All other secondary endpoints, time to cytotoxic chemotherapy, and time to a symptomatic skeletal event (SSE), demonstrated a benefit in favor of darolutamide.

Adverse reactions occurring more frequently in the darolutamide plus ADT arm (=2% absolute increase in frequency compared to placebo plus ADT) were fatigue (16% vs. 11%), pain in extremity (6% vs. 3%), and rash (3% vs. 1%). Discontinuation due to adverse events occurred in 9% of patients in both arms of the study.

About the ARAMIS trial

The approval of darolutamide in Japan is based on the results of the ARAMIS trial, a randomized (2:1), double-blind, placebo-controlled, multi-center Phase III study which evaluated the safety and efficacy of the compound in patients with nmCRPC who are currently being treated with androgen deprivation therapy (ADT) and are at high risk for developing metastatic disease. In the clinical study, 1,509 patients were randomized in a 2:1 ratio to receive 600 mg of darolutamide orally twice daily or placebo along with ADT. Patients with a history of seizure were allowed in the study.

About darolutamide

Darolutamide is an 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. Darolutamide is also being investigated in a Phase III study in metastatic hormone-sensitive prostate cancer (ARASENS trial). Information about these trials can be found at www.clinicaltrials.gov.

The product is also approved in the U.S. and Brazil under the brand name Nubeqa®. It is currently not approved by the European Medicines Agency.

About castration-resistant prostate cancer (CRPC)

Prostate cancer is the second most commonly diagnosed malignancy in men worldwide.2 In 2018, an estimated 1.2 million men were diagnosed with prostate cancer, and about 358,000 died from the disease worldwide.2 Prostate cancer is the fifth leading cause of death from cancer in men.2 Prostate cancer results from the abnormal proliferation of cells within the prostate gland, which is part of a man’s reproductive system.3 It mainly affects men over the age of 50, and the risk increases with age.4

Treatment options range from surgery to radiation treatment to therapy using hormone-receptor antagonists, i.e., substances that stop the formation of testosterone or prevent its effect at the target location.5 However, in nearly all cases, the cancer eventually becomes resistant to conventional hormone therapy.6

CRPC is an advanced form of the disease where the cancer keeps progressing despite ADT treatment, even when the amount of testosterone is reduced to very low levels in the body.1,7 In men with progressive nmCRPC, a rapid prostate specific antigen (PSA) doubling time has been consistently associated with reduced time to first metastasis and death.1

Contact persons:

Christer Nordstedt, PhD, MD, Senior Vice President, Research and Development, Orion Corporation
Tel. +358 10 426 2099
christer.nordstedt@orion.fi

Contact person for investors:
Tuukka Hirvonen, Investor Relations, Orion Corporation
Tel. +358 50 966 2721
tuukka.hirvonen@orion.fi

Contact person for media:
Terhi Ormio, Vice President, Communications, Orion Corporation
Tel. +358 50 966 4646
terhi.ormio@orion.fi

References:

1. Howard, Lauren; Moreira, Daniel M; DeHoedt, Amanda; Aronson, William J., et al. Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer. BJU Int 2017;120: E80-E86.

2. GLOBOCAN 2018: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2018. Prostate Cancer. https://onlinelibrary.wiley.com/doi/epdf/10.3322/caac.21492. Accessed July 2019.

3. American Cancer Society. What is Prostate Cancer? https://www.cancer.org/content/dam/CRC/PDF/Public/8793.00.pdf. Accessed July 2019.

4. American Cancer Society. Prostate Cancer Risk Factors. https://www.cancer.org/content/dam/CRC/PDF/Public/8794.00.pdf. Accessed July 2019.

5. National Cancer Institute. Hormone Therapy for Prostate Cancer. https://www.cancer.gov/types/prostate/prostate-hormone-therapy-fact-sheet. Accessed July 2019.

6. Nakazawa, Mary; Paller, Channing; Kyprianou, Natasha. Mechanisms of Therapeutic Resistance in Prostate Cancer. Curr Oncol Rep (2017) 19:13.

7. Mayo Clinic. Prostate cancer screening: Should you get a PSA test? https://www.mayoclinic.org/tests-procedures/psa-test/in-depth/prostate-cancer/art-20048087. Accessed July 2019.

Publisher:
Orion Corporation
Communications
Orionintie 1A, FI-02200 Espoo, Finland
www.orion.fi

Orion is a globally operating Finnish pharmaceutical company – a builder of well-being. Orion develops, manufactures and markets human and veterinary pharmaceuticals and active pharmaceutical ingredients. The company is continuously developing new drugs and treatment methods. The core therapy areas of Orion’s pharmaceutical R&D are central nervous system (CNS) disorders, oncology and respiratory diseases for which Orion develops inhaled Easyhaler® pulmonary drugs. Orion’s net sales in 2018 amounted to EUR 977 million and the company had about 3,200 employees at the end of the year. Orion’s A and B shares are listed on Nasdaq Helsinki.

Record changed: 2023-06-05