AUA 2025: New Data from Post-Hoc Analyses Shared on Ultra-Low Prostate-Specific Antigen (PSA) Response in Patients with Metastatic Hormone-Sensitive Prostate Cancer Receiving NUBEQA® (darolutamide) plus Androgen Deprivation Therapy (ADT)

• New analyses from the pivotal Phase III ARANOTE trial in men with metastatic hormone-sensitive prostate cancer (mHSPC) demonstrated an association between more ultra-low prostate-specific androgen (PSA) responses (<0.02 ng/mL) with NUBEQA® (darolutamide) plus androgen deprivation therapy (ADT) (42.6%) compared to placebo plus ADT (7.8%). NUBEQA plus ADT demonstrated it had more ultra-low (<0.02 ng/mL) PSA responses (42.6%) compared to placebo plus ADT (7.8%). 

• Ultra-low PSA responses were correlated with relevant clinical outcomes including: prolonged radiographic progression-free survival (rPFS; HR 0.09; 95% CI: 0.05 - 0.16) and delayed time to metastatic castration-resistant prostate cancer (mCRPC; HR 0.07; 95% CI: 0.04 - 0.11) 

• The results were presented at the 2025 American Urological Association (AUA) Annual Meeting
   

WHIPPANY, N.J., April 29, 2025 – New post-hoc analyses from the investigational Phase III ARANOTE trial showed that patients receiving NUBEQA® (darolutamide) plus androgen deprivation therapy (ADT) were more likely to experience an ultra-low (<0.02 ng/mL) prostate specific androgen (PSA) response (42.6%) at any time versus patients receiving placebo plus ADT (7.8%), with ultra-low response rates in the NUBEQA group being higher than in the placebo group regardless of baseline PSA. 1 The post-hoc analyses from the pivotal ARANOTE trial also showed that in patients receiving NUBEQA plus ADT, achieving ultra-low PSA response correlated with prolonged radiographic progression-free survival (rPFS) time (HR 0.09; 95% CI: 0.05–0.16), time to metastatic castration-resistant prostate cancer (mCRPC) (HR 0.07; 95% CI: 0.04–0.11) and time to PSA progression (HR 0.02; 95% CI: 0.01–0.05).¹

The safety profile of NUBEQA was independent of PSA response, with lower treatment discontinuation rates due to treatment emergent adverse events (TEAEs) in patients receiving NUBEQA plus ADT versus placebo.¹

The results were presented today at the 2025 American Urological Association (AUA) Annual Meeting in Las Vegas, Nevada. NUBEQA is indicated in the U.S. for the treatment of adult patients with metastatic hormone-sensitive prostate cancer (mHSPC) in combination with docetaxel and for the treatment of adult patients with non-metastatic castration-resistant prostate cancer (nmCRPC).²

Prostate cancer is the second most common cancer in men.³ Only 30% of those diagnosed with mHSPC will survive five years or more after diagnosis.⁴ Most people with mHSPC eventually progress to mCRPC, a condition with limited long-term survival.^5,6

“The subgroup analyses of the ARANOTE trial contribute to the valuable insights of the management of metastatic hormone-sensitive prostate cancer and equip physicians with additional data to help inform treatment options,” said Dr. Neal Shore, Medical Director, Carolina Urologic Research Center and Urologist at AUC Urology Specialists, Myrtle Beach, South Carolina. 

About the ARANOTE Trial7
The ARANOTE trial (NCT04736199) is a Phase III, randomized, double-blind, placebo-controlled trial designed to assess the efficacy and safety of NUBEQA in combination with standard ADT in patients with mHSPC. A total of 669 patients were randomized 2:1 to receive either 600 mg of NUBEQA (n=446) or placebo (n=223) twice daily in addition to ADT.

The primary endpoint of the ARANOTE trial was rPFS, which was statistically significant for the NUBEQA arm vs placebo arm (HR: 0.54; 95% CI: 0.41-0.71; P < 0.0001), measured as time from randomization to date of first documented radiological disease progression or death due to any cause, whichever occurs first. Secondary endpoints include overall survival (OS; time to death from any cause), time to first castration-resistant event, time to initiation of subsequent anti-cancer therapy, time to PSA progression, PSA undetectable rates, time to pain progression, and safety assessments.

Initial results from pivotal Phase III ARANOTE trial (n=669), published in The Journal of Clinical Oncology and presented at the 2024 European Society for Medical Oncology (ESMO) Congress, demonstrated a statistically significant improvement in rPFS with a 46% reduction in the risk of radiologic progression or death (HR 0.54; 95% CI: 0.41-0.71; P<0.0001) compared to placebo plus ADT.⁸

About NUBEQA® (darolutamide)²
NUBEQA® (darolutamide) is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription.

NUBEQA is developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company.

NUBEQA 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

IMPORTANT SAFETY INFORMATION

Warnings & Precautions
Ischemic Heart Disease – In a study of patients with nmCRPC (ARAMIS), ischemic heart disease occurred in 3.2% of patients receiving NUBEQA versus 2.5% receiving placebo, including Grade 3-4 events in 1.7% vs. 0.4%, respectively. Ischemic events led to death in 0.3% of patients receiving NUBEQA vs. 0.2% receiving placebo. In a study of patients with mHSPC (ARASENS), ischemic heart disease occurred in 3.2% of patients receiving NUBEQA with docetaxel vs. 2% receiving placebo with docetaxel, including Grade 3-4 events in 1.3% vs. 1.1%, respectively. Ischemic events led to death in 0.3% of patients receiving NUBEQA with docetaxel vs. 0% receiving placebo with docetaxel. Monitor for signs and symptoms of ischemic heart disease. Optimize management of cardiovascular risk factors, such as hypertension, diabetes, or dyslipidemia. Discontinue NUBEQA for Grade 3-4 ischemic heart disease.

Seizure – In ARAMIS, Grade 1-2 seizure occurred in 0.2% of patients receiving NUBEQA vs. 0.2% receiving placebo. Seizure occurred 261 and 456 days after initiation of NUBEQA. In ARASENS, seizure occurred in 0.6% of patients receiving NUBEQA with docetaxel, including one Grade 3 event, vs. 0.2% receiving placebo with docetaxel. Seizure occurred 38 to 340 days after initiation of NUBEQA. It is unknown whether antiepileptic medications will prevent seizures with NUBEQA. Advise patients of the risk of developing a seizure while receiving NUBEQA and of engaging in any activity where sudden loss of consciousness could cause harm to themselves or others. Consider discontinuation of NUBEQA in patients who develop a seizure during treatment.

Embryo-Fetal Toxicity – Safety and efficacy of NUBEQA have not been established in females. NUBEQA can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception during treatment with NUBEQA and for 1 week after the last dose.

Adverse Reactions
In ARAMIS, serious adverse reactions occurred in 25% of patients receiving NUBEQA vs. 20% of patients receiving placebo. Serious adverse reactions in ≥1% of patients who received NUBEQA included urinary retention, pneumonia, and hematuria. Fatal adverse reactions occurred in 3.9% of patients receiving NUBEQA vs. 3.2% of patients receiving placebo. Fatal adverse reactions in patients who received NUBEQA included death (0.4%), cardiac failure (0.3%), cardiac arrest (0.2%), general physical health deterioration (0.2%), and pulmonary embolism (0.2%). The most common adverse reactions (>2% with a ≥2% increase over placebo), including laboratory test abnormalities, were increased AST, decreased neutrophil count, fatigue, increased bilirubin, pain in extremity and rash. Clinically relevant adverse reactions occurring in ≥2% of patients treated with NUBEQA included ischemic heart disease and heart failure.

In ARASENS, serious adverse reactions occurred in 45% of patients receiving NUBEQA with docetaxel vs. 42% of patients receiving placebo with docetaxel. Serious adverse reactions in ≥2% of patients who received NUBEQA with docetaxel included febrile neutropenia (6%), decreased neutrophil count (2.8%), musculoskeletal pain (2.6%), and pneumonia (2.6%). Fatal adverse reactions occurred in 4% of patients receiving NUBEQA with docetaxel vs. 4% of patients receiving placebo with docetaxel. Fatal adverse reactions in patients who received NUBEQA included COVID-19/COVID-19 pneumonia (0.8%), myocardial infarction (0.3%), and sudden death (0.3%). The most common adverse reactions (≥10% with a ≥2% increase over placebo with docetaxel) were constipation, rash, decreased appetite, 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. Clinically relevant adverse reactions in <10% of patients who received NUBEQA with docetaxel included fractures, ischemic heart disease, seizures, and drug-induced liver injury.

Drug Interactions
Effect of Other Drugs on NUBEQA – Combined P-gp and strong or moderate CYP3A4 inducers decrease NUBEQA exposure, which may decrease NUBEQA activity. Avoid concomitant use.

Combined P-gp and strong CYP3A4 inhibitors increase NUBEQA exposure, which may increase the risk of NUBEQA adverse reactions. Monitor more frequently and modify NUBEQA dose as needed.

Effects of NUBEQA on Other Drugs – NUBEQA inhibits breast cancer resistance protein (BCRP) transporter. Concomitant use increases exposure (AUC) and maximal concentration of BCRP substrates, which may increase the risk of BCRP substrate-related toxicities. Avoid concomitant use where possible. If used together, monitor more frequently for adverse reactions, and consider dose reduction of the BCRP substrate.

NUBEQA inhibits OATP1B1 and OATP1B3 transporters. Concomitant use may increase plasma concentrations of OATP1B1 or OATP1B3 substrates. Monitor more frequently for adverse reactions and consider dose reduction of these substrates.

Review the Prescribing Information of drugs that are BCRP, OATP1B1, and OATP1B3 substrates when used concomitantly with NUBEQA.

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 common cancer in men and the fifth most common cause of cancer death in men worldwide.3.9 In 2020, an estimated 1.4 million men were diagnosed with prostate cancer, including almost 300,000 cases in the U.S., and about 375,000 died from the disease worldwide.^10,11

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 10% of men will already present with mHSPC when first diagnosed.12,13,14 Men with mHSPC will start their treatment with hormone therapy, such as ADT, androgen receptor inhibitor (ARi) plus ADT or a combination of the chemotherapy docetaxel and ADT. Despite this treatment, most men with mHSPC will eventually progress to mCRPC, a condition with limited survival.^5,6

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. In line with its mission, “Health for all, Hunger for none,” the company’s products and services are designed to help people and the planet thrive by supporting efforts to master the major challenges presented by a growing and aging global population. Bayer is committed to driving sustainable development and generating 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 2023, the Group employed around 100,000 people and had sales of 47.6 billion euros. R&D expenses before special items amounted to 5.8 billion euros. 

Media Contact:
Polina Miklush, Tel + 862.431.8817 
Email: polina.miklush@bayer.com

Forward-Looking Statements 
This release may contain forward-looking statements based on current assumptions and forecasts made by Bayer management. Various known and unknown risks, uncertainties and other factors could lead to material differences between the actual future results, financial situation, development or performance of the company and the estimates given here. These factors include those discussed in Bayer’s public reports which are available on the Bayer website at www.bayer.com. The company assumes no liability whatsoever to update these forward-looking statements or to conform them to future events or developments.

References
^{1.    Shore N et al. Ultra-low PSA Response (<0.02 ng/mL) With Darolutamide Plus ADT in ARANOTE Correlates With Greatly Improved Clinical Outcomes. Abstract IP26-07. Presented at AUA 2025.
2.    NUBEQA® (darolutamide) [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; October 2023.
3.    Bray F et al. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.21834. Accessed: March 2025.
4.    Ng, K et al. Oncol Ther. 2020;8:209–230. 
5.    Siegel DA et al. MMWR Morb Mortal Wkly Rep. 2020;69:1473–1480. 
6.    Hahn AW et al. Am Soc Clin Oncol Educ Book. 2018 May 23;38:363-371. 
7.    ClinicalTrials.gov NCT04736199. Darolutamide in Addition to ADT Versus ADT in Metastatic Hormone-sensitive Prostate Cancer (ARANOTE). https://www.clinicaltrials.gov/study/NCT04736199. Accessed: March 2025.  
8.    Journal of Clinical Oncology (ascopubs.org). Darolutamide in Combination With Androgen-Deprivation Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer From the Phase III ARANOTE Trial. https://ascopubs.org/doi/10.1200/JCO-24-01798. September 2024. 
9.    Hyuna S et al. Ca Cancer J Clin 2021; 71:209–249.
10.    Prostate Cancer: Statistic. Cancer.Net. https://www.cancer.net/cancer-types/prostate-cancer/statistics. Accessed: March 2025. 
11.    American Cancer Society. Cancer Facts & Figures 2024. https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/2024-cancer-facts-figures.html. Accessed: March 2025
12.    Piombino C et al. Cancers (Basel). 2023 Oct 11;15(20):4945.
13.    Helgstrand JT et al. Cancer. 2018;124(14):2931-2938.
14.    Buzzoni C et al. Eur. Urol. 2015;68:885–890}