U.S. FDA Approves Additional Indication of NUBEQA® (darolutamide) in Combination with Docetaxel for the Treatment of Metastatic Hormone-Sensitive Prostate Cancer (mHSPC)

  • NUBEQA now has indications in both metastatic hormone-sensitive prostate cancer (mHSPC) and non-metastatic castration-resistant prostate cancer (nmCRPC)1
  • Today’s approval under the FDA’s Real-Time Oncology Review (RTOR) pilot program was based on the pivotal Phase III ARASENS trial, which showed a significant overall survival (OS) benefit with NUBEQA plus androgen deprivation therapy (ADT) and docetaxel compared to ADT and docetaxel1
  • NUBEQA is the only androgen receptor inhibitor (ARi) approved in combination with docetaxel for mHSPC, demonstrating a 32% reduction in the risk of death compared to docetaxel alone and with a proven tolerability profile1

WHIPPANY, NJ, USA I August 05, 2022 I Bayer announced today the U.S. Food and Drug Administration (FDA) has approved a supplemental New Drug Application (sNDA) for the oral androgen receptor inhibitor (ARi) NUBEQA® (darolutamide) with docetaxel for the treatment of adult patients with metastatic hormone-sensitive prostate cancer (mHSPC).1

The approval is based on results of the Phase III ARASENS trial that demonstrated a statistically significant increase in overall survival (OS), the trial’s primary endpoint, with a reduction in the risk of death by 32% for those treated with NUBEQA plus androgen deprivation therapy (ADT) and docetaxel compared to ADT and docetaxel (HR=0.68, 95% CI 0.57-0.80; P<0.0001). Treatment with NUBEQA plus ADT and docetaxel also resulted in a statistically significant delay in time to pain progression (HR=0.79, 95% CI 0.66-0.95; P=0.006).1

The ARASENS results were presented earlier this year at the 2022 ASCO GU Cancers Symposium and simultaneously published in The New England Journal of Medicine.2 NUBEQA is also indicated for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC). NUBEQA is being investigated in further studies across various stages of prostate cancer.

Incidence of adverse reactions was similar between both study arms. Adverse reactions reported for NUBEQA with docetaxel above 10% with a ≥2% increase over placebo with docetaxel were constipation (23% versus 20%), decreased appetite (19% versus 13%), rash (19% versus 15%), hemorrhage (18% versus 13%), increased weight (18% versus 16%), and hypertension (14% versus 9%). Serious adverse reactions occurred in 45% of patients receiving NUBEQA with docetaxel and in 42% of patients receiving placebo with docetaxel. Fatal adverse reactions occurred in 4% of patients receiving NUBEQA with docetaxel and in 4% of patients receiving placebo with docetaxel.1

“NUBEQA plus ADT and docetaxel has shown significant benefit in overall survival and a favorable safety profile for patients with metastatic hormone-sensitive prostate cancer,” said Matthew Smith, M.D., Ph.D., Director of the Genitourinary Malignancies Program, Massachusetts General Hospital Cancer Center. “This new indication for NUBEQA is particularly meaningful, as it highlights its proven tolerability and provides a new option for patients.”

Prostate cancer remains the second leading cancer-related cause of death among men in the U.S., with up to one-third of patients developing metastatic disease.3,4 The incidence of mHSPC has increased by 72% in the U.S. over the past 10 years.5 Approximately one in three patients who are diagnosed with mHSPC survive the disease five years or longer, with most eventually experiencing progression to castration-resistant prostate cancer (CRPC).4,5

“With compelling data from the Phase III ARASENS and ARAMIS trials, NUBEQA has demonstrated significant efficacy in mHSPC and nmCRPC,” said Christine Roth, Member of the Executive Committee of Bayer’s Pharmaceutical Division and Head of the Oncology SBU at Bayer. “The expansion of NUBEQA’s indication to reach a broader population in the U.S. reaffirms Bayer’s commitment to provide proven and tolerable treatment options to eligible patients across different stages of prostate cancer.”

“Prostate cancer is the most common cancer among men in the U.S., with chances of survival decreasing dramatically for those diagnosed with mHSPC compared to localized prostate cancer,” said Charles J. Ryan, M.D., President and Chief Executive Officer, Prostate Cancer Foundation (PCF). “This approval adds a different treatment approach for mHSPC patients and their physicians to choose from.”

The application received Priority Review designation granted by the FDA and was submitted under the FDA’s Real-Time Oncology Review (RTOR) pilot program, which aims to provide a more efficient review process of applications to ensure that safe and effective cancer treatments are available to patients as early as possible. Ongoing reviews are also being conducted under the FDA Oncology Center of Excellence's (OCE) Project Orbis initiative, which provides a framework for concurrent submission and review of cancer treatments among participating international health authorities.

About the ARASENS Trial6

The ARASENS trial (NCT02799602) is the only randomized, Phase III, multi-center, double-blind, placebo-controlled trial prospectively designed to compare the use of a second-generation androgen receptor inhibitor (ARi) (NUBEQA) plus androgen deprivation therapy (ADT) and the chemotherapy docetaxel to ADT and docetaxel (a guideline recommended treatment) 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 NUBEQA twice a day or matching placebo, plus ADT and 75 mg/m2 of docetaxel, for 6 cycles. Treatment with NUBEQA plus ADT or ADT continued until symptomatic progressive disease, change of antineoplastic therapy, unacceptable toxicity, death, or withdrawal.

The primary endpoint of this trial was overall survival (OS). Time to pain progression was a secondary endpoint.

Permanent discontinuation of NUBEQA due to adverse reactions occurred in 14% of patients treated in the NUBEQA with docetaxel arm. The most common adverse reactions which resulted in permanent discontinuation of NUBEQA were rash (1.1%), musculoskeletal pain (0.9%), and increased aspartate aminotransferase (AST) (0.9%). Dosage interruptions of NUBEQA due to adverse reactions occurred in 23% of patients treated in the NUBEQA with docetaxel arm. The most common adverse reactions (>2%) requiring dosage interruption of NUBEQA were increased alanine aminotransferase (ALT) (3.2%), increased AST (3.1%) and febrile neutropenia (2.1%). Dosage reductions of NUBEQA due to adverse reactions occurred in 9% of patients treated in the NUBEQA with docetaxel arm. The most common adverse reactions (>2%) requiring dosage reduction of NUBEQA were increased ALT (2.8%) and increased AST (2.5%). The most common adverse reactions (≥10% with a ≥2% increase over placebo with docetaxel) were constipation, decreased appetite, rash, hemorrhage, increased weight, and hypertension. The most common laboratory test abnormalities (≥30%) were anemia, hyperglycemia, decreased lymphocyte count, decreased neutrophil count, increased AST, increased ALT, and hypocalcemia.

About NUBEQA® (darolutamide)1

NUBEQA is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription.1

On July 30, 2019, the FDA approved NUBEQA® (darolutamide) based on the ARAMIS trial, a randomized, double-blind, placebo-controlled, multi-center Phase III study, which evaluated the safety and efficacy of oral NUBEQA in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) who were receiving a concomitant gonadotropin-releasing hormone (GnRH) analog or had a bilateral orchiectomy. In the clinical study, 1,509 patients were randomized in a 2:1 ratio to receive 600 mg of NUBEQA orally twice daily in combination with androgen deprivation therapy (ADT), or ADT alone. The primary efficacy endpoint was metastasis-free survival (MFS). NUBEQA is also being investigated in further studies across various stages of prostate cancer, including in the ARANOTE Phase III trial evaluating NUBEQA plus ADT versus ADT alone for metastatic hormone-sensitive prostate cancer (mHSPC), as well as in the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) led international Phase III co-operative group DASL-HiCaP (ANZUP1801) trial evaluating NUBEQA as an adjuvant treatment for localized prostate cancer with very high risk of recurrence. Information about these trials can be found at www.clinicaltrials.gov.

Developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company, NUBEQA is indicated for the treatment of adults with nmCRPC and mHSPC.1 The approvals of NUBEQA for nmCRPC in the U.S., European Union (EU), and other global markets have been based on the pivotal Phase III ARAMIS trial data evaluating the efficacy and safety of NUBEQA plus ADT compared to ADT alone.1 Filings in other regions are underway or planned.


NUBEQA® (darolutamide) is an androgen receptor inhibitor indicated for the treatment of adult patients with:

  • Non-metastatic castration-resistant prostate cancer (nmCRPC)
  • Metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel

For important risk and use information about NUBEQA, please see the accompanying full Prescribing Information.

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.7

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.8,9 Upon relapse, when the disease will metastasize or spread, the disease is hormone-sensitive and androgen deprivation therapy (ADT) is the cornerstone of treatment. 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 docetaxel chemotherapy and ADT. Despite these treatments, a large proportion of men with mHSPC will eventually experience progression to metastatic castration-resistant prostate cancer (mCRPC), a condition with high morbidity and limited survival.3,5

About Oncology at Bayer

Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer includes six marketed products and several other assets in various stages of clinical development. Together, these products reflect the company’s approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.

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 help people and planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to drive sustainable development and generate a positive impact with its businesses. At the same time, the Group aims to increase its earning power and create value through innovation and growth. The Bayer brand stands for trust, reliability, and quality throughout the world. In fiscal 2021, the Group employed around 100,000 people and had sales of 44.1 billion euros. R&D expenses before special items amounted to 5.3 billion euros. For more information, go to www.bayer.com.


  1. NUBEQA® (darolutamide) tablets [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, August 2022.
  2. Smith M., Hussain M., Saad F. et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022.
  3. Siegel DA, O’Neil ME, Richards TB, Dowling NF, Weir HK. Prostate Cancer Incidence and Survival, by Stage and Race/Ethnicity — United States, 2001–2017. MMWR Morb Mortal Wkly Rep 2020;69:1473–1480. http://dx.doi.org/10.15585/mmwr.mm6941a1.
  4. Ng, K., Smith, S., Shamash, J. Metastatic Hormone-Sensitive Prostate Cancer (mHSPC): Advances and Treatment Strategies in the First-Line Setting. Oncol Ther 8, 209–230 (2020). https://doi.org/10.1007/s40487-020-00119-z.
  5. Hahn AW, Higano CS, Taplin ME, Ryan CJ, Agarwal N. Metastatic Castration-Sensitive Prostate Cancer: Optimizing Patient Selection and Treatment. Am Soc Clin Oncol Educ Book. 2018 May 23;38:363-371. https://doi.org/10.1200/edbk_200967.
  6. ClinicalTrials.gov NCT02799602. ODM-201 in Addition to Standard ADT and Docetaxel in Metastatic Castration Sensitive Prostate Cancer (ARASENS). https://clinicaltrials.gov/ct2/show/NCT02799602.
  7. Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: A Cancer Journal for Clinicians. https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.3322/caac.21660.Accessed August 2022.
  8. Cancer.Net 2020: Prostate Cancer Statistics. https://www.cancer.net/cancer-types/prostate-cancer/statistics. Accessed August 2022.
  9. American Cancer Society: Hormone Therapy for Prostate Cancer. https://www.cancer.org/cancer/prostate-cancer/treating/hormone-therapy.html. Accessed August 2022.


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