U.S. FDA approves darolutamide, a new treatment for men with non-metastatic castration-resistant prostate cancer (nmCRPC)

ORION CORPORATION PRESS RELEASE 31 JULY 2019 at 7.30 EEST             
         

U.S. FDA approves darolutamide, a new treatment for men with non-metastatic castration-resistant prostate cancer (nmCRPC)

Approval of darolutamide 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. Darolutamide was approved under the FDA Priority Review designation.

The U.S. Food and Drug Administration (FDA) has granted approval to darolutamide, a non-steroidal androgen receptor inhibitor (ARi), under the brand name Nubeqa®. The FDA approval is for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and is based on the Phase III ARAMIS trial showing darolutamide plus androgen deprivation therapy (ADT) demonstrated a highly significant improvement in the primary efficacy endpoint of metastasis-free survival (MFS), with a median of 40.4 months versus 18.4 months for placebo plus ADT group (p<0.0001).

The compound, which is developed jointly by Orion Corporation and Bayer was approved under the FDA Priority Review designation, which is reserved for medicines that may provide significant improvements in the safety or effectiveness of the treatment for serious conditions. The androgen receptor inhibitor (ARi) has 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.

“Patients with nmCRPC are usually asymptomatic, but have a rising blood 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 a new therapeutic option that addresses these questions” said Christer Nordstedt, Senior Vice President, Research and Development, Orion Corporation.

Prostate cancer that has not spread to other parts of the body but is associated with a rising blood prostate-specific antigen (PSA) level even when the amount of testosterone is reduced with ADT treatment to very low levels in the body is known as nmCRPC. In the U.S., over 73,000 men are estimated to have a CRPC diagnosis in 2019. About one-third of men with nmCRPC go on to develop metastases within two years.

“The approval of Nubeqa® in the US is a significant event for prostate cancer patients, their caregivers, healthcare professionals as well as for Orion and Bayer. The fact that Orion’s latest oncology invention, Nubeqa was approved under the FDA Priority Review process, speaks for the value of treatment option,” said Timo Lappalainen, President and CEO of Orion Corporation.

In the ARAMIS trial, overall survival (OS) and time to pain progression were additional secondary efficacy endpoints. A positive trend in OS was  observed; OS data were not yet mature at the time of final MFS analysis. 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, demonstrated a benefit in favor of darolutamide.  

The only adverse reactions occurring more frequently in the darolutamide plus ADT arm (≥2 percent over placebo plus ADT) were fatique (16% vs. 11%), pain in extremity (6% vs. 3%), and rash (3% vs. 1%). Discontinuation due to adverse events occurred in 9 percent of patients in both arms of the study.

Preclinical studies demonstrated lower blood-brain barrier penetration of darolutamide compared to other currently available androgen receptor inhibitors. A high concentration of these compounds in the central nervous system may lead to undesired side effects.

Bayer has filed for approval of the compound  in the European Union (EU), Japan and with other health authorities.

About the ARAMIS trial
The FDA approval of darolutamide is based on the ARAMIS trial, a randomized (2:1), double-blind, placebo-controlled, multi-center Phase III study which evaluated the safety and efficacy of oral darolutamide 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.

Darolutamide has been approved in the U.S. under the brand name Nubeqa®. It is currently not approved by the European Medicines Agency or any other health authority outside the U.S.

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

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. However, in nearly all cases, the cancer eventually becomes resistant to conventional hormone therapy.

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. The field of treatment options for castration-resistant patients is evolving rapidly, but until recently, there have been no effective treatment options for CRPC patients who have rising PSA levels while on ADT and no detectable metastases. In men with progressive nmCRPC, a rapid PSA doubling time has been consistently associated with reduced time to first metastasis and death.

About Orion
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.

About Bayer
Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to benefit people by supporting efforts to overcome the major challenges presented by a growing and aging global population. At the same time, the Group aims to increase its earning power and create value through innovation and growth. Bayer is committed to the principles of sustainable development, and the Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2018, the Group employed around 117,000 people and had sales of 39.6 billion euros. Capital expenditures amounted to 2.6 billion euros, R&D expenses to 5.2 billion euros. For more information, go to:
http://bayer.com

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

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.

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