Orion Corporation and Bayer today announced that the U.S. Food and Drug Administration (FDA) has accepted the New Drug Application (NDA) for review and granted Priority Review for darolutamide for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC) in the U.S.
The NDA and Priority Review status were based on data from the Phase III ARAMIS trial in men with nmCRPC.1 Darolutamide is an investigational, non-steroidal androgen receptor (AR) antagonist with a distinct chemical structure that binds with high affinity to the receptor, inhibiting the growth of prostate cancer cells.
"Darolutamide is highly effective in the patient population with non-metastatic castration-resistant prostate cancer, and it has few adverse effects with a profile that parallels that of placebo. We are looking forward to taking the next steps in bringing darolutamide to men with nmCRPC and their treating physicians. With the NDA acceptance for review and Priority Review designation, we are an important step closer to bringing darolutamide to patients as quickly as possible", said Christer Nordstedt, MD, PhD, Senior Vice President, Research and Development, Orion Corporation.
The FDA grants Priority Review for the applications of medicines that, if approved, would provide significant improvements in the safety or effectiveness of the treatment, diagnosis, or prevention of serious conditions when compared to standard applications.
Bayer recently submitted an application to the European Medicines Agency and the Ministry of Health, Labor and Welfare (MHLW) in Japan. Bayer is also in discussions with other health authorities regarding submissions.
Darolutamide is being developed jointly by Orion Corporation and Bayer.
The ARAMIS trial is a randomized, Phase III, multi-center, double-blind, placebo-controlled trial evaluating the safety and efficacy of oral darolutamide in patients with nmCRPC who are currently being treated with ADT and are at high risk for developing metastatic disease. 1,509 patients were randomized in a 2:1 ratio to receive 600 mg of darolutamide twice a day or placebo along with ADT.
Darolutamide is a non-steroidal androgen receptor (AR) antagonist 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. In preclinical studies, darolutamide demonstrated lower blood-brain barrier penetration compared to other currently available AR antagonists.2
In addition to the Phase III trial ARAMIS in men with nmCRPC, darolutamide is also being investigated in a Phase III study in metastatic hormone-sensitive prostate cancer (ARASENS). Information about these trials can be found at www.clinicaltrials.gov.
Darolutamide is not approved by the U.S. FDA, the European Medicines Agency or any other health authority.
About castration-resistant prostate cancer (CRPC)
Prostate cancer is the second most commonly diagnosed malignancy in men worldwide.3 In 2018, an estimated 1.2 million men were diagnosed with prostate cancer, and about 358,000 died from the disease worldwide.3 Prostate cancer is the fifth leading cause of death from cancer in men.3 Prostate cancer results from the abnormal proliferation of cells within the prostate gland, which is part of a man's reproductive system.4 It mainly affects men over the age of 50, and the risk increases with age.5 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.6 However, in nearly all cases, the cancer eventually becomes resistant to conventional hormone therapy.7
CRPC is an advanced form of the disease where the cancer keeps progressing 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 approved treatment options for CRPC patients who have rising prostate-specific antigen (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.8
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.
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 www.bayer.com.
Christer Nordstedt, MD, PhD, Senior Vice President, Research and Development, Orion Corporation
Tel. +358 10 426 2099
Vice President, Communications, Orion Corporation
Tel. +358 (0)50 966 4646
- Fizazi, Karim; Shore, Neal; Tammela, Teuvo, et al. Darolutamide in Nonmetastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2019; doi: 10.1056/NEJMoa1815671.
- Moilanen, Anu-Maarit; Riikonen, Reetta; Oksala, Riikka, et al. Discovery of ODM-201, a new-generation androgen receptor inhibitor targeting resistance mechanisms to androgen signaling-directed prostate cancer therapies. Sci Rep. 2015;5:12007
- GLOBOCAN 2018: Estimated Cancer Incidence, Mortality and Prevalence Worldwide in 2018. Prostate Cancer. http://gco.iarc.fr/today/data/pdf/fact-sheets/cancers/cancer-fact-sheets-19.pdf. Accessed February 2019.
- American Cancer Society. What is Prostate Cancer? https://www.cancer.org/content/dam/CRC/PDF/Public/8793.00.pdf. Accessed February 2019.
- American Cancer Society. Prostate Cancer Risk Factors. https://www.cancer.org/content/dam/CRC/PDF/Public/8794.00.pdf. Accessed February 2019.
- National Cancer Institute. Hormone Therapy for Prostate Cancer. https://www.cancer.gov/types/prostate/prostate-hormone-therapy-fact-sheet. Accessed February 2019.
- Nakazawa, Mary; Paller, Channing; Kyprianou, Natasha. Mechanisms of Therapeutic Resistance in Prostate Cancer. Curr Oncol Rep (2017) 19:13.
- 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.
Orionintie 1A, FI-02200 Espoo, Finland
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. For more information, go to www.orion.fi/en