ORION CORPORATION PRESS RELEASE 11 March 2022 at 8.30 EET
Orion’s collaboration partner Bayer submits application for additional indication of darolutamide in Japan
Submission to the Ministry of Health, Labor and Welfare (MHLW) in Japan for an additional indication of darolutamide in prostate cancer with distant metastases
Application is based on data from the pivotal Phase III ARASENS trial showing that the use of darolutamide plus ADT and docetaxel led to a statistically significant improvement in overall survival (OS) compared to ADT plus docetaxel as well as consistent benefits in key secondary endpoints in patients with metastatic hormone-sensitive prostate cancer (mHSPC), with similar overall rates of adverse events (AEs) between study arms
Additional submissions in other regions planned or underway by Bayer
Broad development program underway with three additional ongoing or planned large clinical studies for darolutamide across various stages of prostate cancer
Orion’s collaboration Bayer today announced the submission to the Ministry of Health, Labor and Welfare (MHLW) in Japan for an additional indication for the oral androgen receptor inhibitor (ARi) darolutamide. The application seeks marketing authorisation for darolutamide in combination with docetaxel and androgen deprivation therapy (ADT) for the treatment of patients with prostate cancer with distant metastasis. Darolutamide is already marketed 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.
The MHLW submission is based on positive results from the pivotal Phase III ARASENS trial recently presented at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) and published in The New England Journal of Medicine. Results demonstrated a statistically significant improvement in overall survival for darolutamide plus ADT and docetaxel compared to ADT plus docetaxel in men with metastatic hormone-sensitive prostate cancer (mHSPC).
Darolutamide is already approved in more than 60 markets around the world, including the U.S., the European Union (EU), Japan and China, 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. The product is developled jointly by Orion and Bayer.
Additional filings for the indication of mHSPC have been made in the US and in the EU, and filings in additional regions are underway or planned by Bayer. The compound is also being investigated in further studies across various stages of prostate cancer, including another Phase III trial in mHSPC (ARANOTE) as well as an ANZUP-led international co-operative group Phase III trial, evaluating darolutamide as an adjuvant treatment for localized prostate cancer with very high risk of recurrence (DASL-HiCaP, ANZUP1801).
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.
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.1
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 metastasize or spread, androgen deprivation therapy (ADT) is the cornerstone of treatment for this hormone-sensitive disease. Approximately 5% of men will already suffer from prostate cancer with distant metastases when first diagnosed. 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 the chemotherapy docetaxel and ADT. Despite these treatments, a large proportion of men with mHSPC will eventually progress 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. A low blood-brain barrier penetration would explain the overall low incidence of central nervous system (CNS)-related adverse events (AEs) compared to placebo as seen in the ARAMIS Phase III trial and the improved verbal learning and memory observed in the darolutamide arm of the Phase II ODENZA trial.
The product is approved under the brand name Nubeqa® in more than 60 markets around the world, including the U.S., EU, Japan, China, for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease. The compound is also being investigated in further studies across various stages of prostate cancer, including another Phase III trial in mHSPC (ARANOTE) as well as an ANZUP-led international co-operative group Phase III trial, evaluating darolutamide as an adjuvant treatment for localized prostate cancer with very high risk of recurrence (DASL-HiCaP, ANZUP1801). Information about these trials can be found at www.clinicaltrials.gov.
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 neurological disorders, oncology and respiratory diseases for which Orion develops inhaled pulmonary medication. Orion's net sales in 2021 amounted to EUR 1,041 million and the company had about 3,350 employees at the end of the year. Orion's A and B shares are listed on Nasdaq Helsinki.
