March 9, 2022: “Bayer announced the submission of a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration (FDA) as well as the submission of a Variation Type II application to the European Medicines Agency (EMA) for the oral androgen receptor inhibitor (ARi) darolutamide.
Bayer is seeking approval for the use of darolutamide in combination with docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC).
The compound 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 submissions are supported by positive results from the Phase III ARASENS trial, showing a statistically significant improvement in overall survival (OS) for darolutamide plus androgen deprivation therapy (ADT) and docetaxel in men with mHSPC.
These results were presented in February at the 2022 ASCO GU Cancers Symposium and simultaneously published in The New England Journal of Medicine.
“For men with mHSPC, there remains a high need for new treatment options that can extend overall survival and delay the progression to CRPC,” said Christine Roth, Member of the Executive Committee of Bayer’s Pharmaceutical Division and Head of the Oncology SBU at Bayer.
“Prostate cancer is a key area of focus at Bayer and the U.S. and EU submissions for darolutamide in mHSPC represent a significant milestone in our commitment to developing treatments that support men with prostate cancer throughout the different stages of the disease.”
Darolutamide is developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company. Additional submissions in mHSPC are planned globally.
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 the only randomized, Phase III, multi-center, double-blind, trial which was prospectively designed to compare the use of a second-generation oral androgen receptor inhibitor (ARi) plus androgen deprivation therapy (ADT) and docetaxel to ADT plus docetaxel (a guideline recommended standard-of-care) in 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.
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 high morbidity and limited survival.
About Nubeqa™ (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 the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (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.
About Prostate Cancer at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments.
The company has the passion and determination to develop new medicines that help improve and extend the lives of people living with cancer. Prostate cancer is the second most commonly diagnosed cancer in men1 and a key area of focus for Bayer.
The company’s franchise includes two products on the market (Nubeqa™ and Xofigo™) and several compounds in development, including a unique approach of advancing targeted alpha therapies.
Bayer is focused on addressing the unique needs of prostate cancer patients, providing treatments that extend their lives throughout the different stages of the disease and allowing them to continue their everyday activities, so that they can live longer, better lives.”
