New Data for NUBEQA® Build on Safety and Efficacy Results Across Subgroups of Patients with Metastatic Hormone-Sensitive Prostate Cancer

• New subgroup analysis from the investigational Phase III ARANOTE trial show that NUBEQA^® (darolutamide) plus androgen deprivation therapy (ADT) improved radiological progression-free survival (rPFS) by 40% (HR 0.60; 95% CI: 0.44-0.80) and 70% (HR 0.30; 95% CI: 0.15-0.60) respectively in patients with high and low-volume metastatic hormone-sensitive prostate cancer (mHSPC), compared to placebo plus ADT
• Additional post-hoc subgroup analysis from the Phase III ARASENS trial showed that patients with mHSPC benefited from NUBEQA in combination with ADT and docetaxel irrespective of age, with consistent improvements in overall survival (OS) across age subgroups (<75 and ≥75 years old; 30% reduction (HR 0.70; 95% CI 0.58-0.84) in the risk of death for patients <75 and 39% reduction (HR 0.61; 95% CI 0.41-0.91) in the risk of death for patients ≥75) compared to placebo plus docetaxel plus ADT
• A retrospective cohort analysis using real-world data evaluated the probability of treatment discontinuation, progression to mCRPC, and PSA responses for patients with mHSPC receiving triplet therapy with NUBEQA in combination with ADT and docetaxel compared to abiraterone plus ADT plus docetaxel
• Results were consistent with the established safety profile of NUBEQA with no new safety signals across cohorts

WHIPPANY, N.J.--(BUSINESS WIRE)--New subgroup data from the investigational Phase III ARANOTE trial show NUBEQA^® (darolutamide) plus androgen-deprivation therapy (ADT) improved radiological progression-free survival (rPFS) in patients with high and low-volume metastatic hormone sensitive (mHSPC) by 40% (hazard ratio [HR] 0.60; 95% confidence interval [CI] 0.44-0.80) and 70% (HR 0.30; 95% CI 0.15-0.60) respectively, compared to placebo plus ADT. The overall incidence of adverse events was low, with incidence similar in the high and low-volume subgroups and consistent with the overall population. The full results were presented during the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) 2025 Congress.

NUBEQA is indicated in the U.S. for the treatment of adult patients with mHSPC in combination with docetaxel and for the treatment of adult patients with non-metastatic castration-resistant prostate cancer (nmCRPC).¹

Full results from the Phase III ARANOTE trial were first presented at the European Society for Medical Oncology (ESMO) Congress in September 2024 and showed that NUBEQA plus ADT significantly reduced the risk of radiological progression or death by 46% compared to placebo plus ADT (HR 0.54; 95% CI 0.41-0.71; P<0.0001), in patients with mHSPC.

Prostate cancer is the second most common cancer in men.² Only 30% of those diagnosed with mHSPC will survive five years or more after diagnosis.³ Most people with mHSPC eventually progress to metastatic castration-resistant prostate cancer (mCRPC), a condition with limited long-term survival.^4,5

“At Bayer, our mission in prostate cancer care is centered on improving patient outcomes across all disease stages. The expanding body of evidence for NUBEQA highlights Bayer’s commitment to supporting the diverse needs of prostate cancer patients,” said Christine Roth, Global Head of Product Strategy and Commercialization at Bayer’s Pharmaceuticals Division. “The data shared at ASCO GU continue to build on the established clinical profile of NUBEQA and providing additional evidence to support the safety and efficacy benefits for patients living with prostate cancer.”

In the ARANOTE trial, patients with mHSPC were randomized 2:1 to receive NUBEQA plus ADT versus placebo plus ADT. High-volume disease was defined by the presence of visceral metastases and/or ≥4 bone metastases with ≥1 beyond the vertebral column/pelvis, as delineated in the CHAARTED criteria. Of 669 patients included in the full analysis set, 472 (71%) had high-volume disease and 197 (29%) had low-volume disease.

The subgroup analysis showed that, in the low-volume (LV) subgroup, NUBEQA plus ADT reduced the risk of radiological progression or death by 70% (HR 0.30; 95% CI: 0.15-0.60) with median rPFS not reached, compared to placebo plus ADT. In the high-volume (HV) subgroup, NUBEQA plus ADT reduced the risk of radiological progression or death by 40% (HR 0.60; 95% CI: 0.44-0.80) with median rPFS of 30.2 months with NUBEQA versus 19.2 months with placebo. Secondary endpoints presented included that NUBEQA delayed time to mCRPC (HV: HR 0.46; 95% CI: 0.36-0.60; LV: HR 0.21; 95% CI: 0.12-0.37) and time to prostate-specific antigen (PSA) progression (HV: HR 0.34; 95% CI: 0.25-0.46; LV: HR 0.19; 95% CI: 0.10-0.37) and a higher proportion achieved PSA <0.2 ng/mL with NUBEQA vs placebo (HV: 54.6% vs 15.5%; LV: 82.6% vs 25.4%) in high and low-volume subgroups. Treatment-emergent adverse events were low and similar across both high- and low-volume subgroups, and consistent with the overall population.

Other data presented at ASCO GU 2025 included an age-related subgroup analysis of the Phase III ARASENS trial and additional real-world data analysis, both in mHSPC patients showing positive responses with NUBEQA in combination with ADT and docetaxel across key clinically relevant endpoints.

Data from the ARASENS subgroup analysis of 1,305 patients with ages ranging from 41-89 years showed that patients with mHSPC benefited from NUBEQA in combination with ADT and docetaxel, irrespective of age (<75 y and ≥75 y). Consistent improvements were seen in overall survival (OS; <75 y HR 0.70; 95% CI 0.58-0.84; ≥75 y HR 0.61; 95% CI 0.41-0.91), time to mCRPC (<75 y HR 0.35; 95% CI 0.30-0.43; ≥75 y HR 0.42; 95% CI 0.28-0.64), and time to initiation of subsequent therapy (<75 y HR 0.40; 95% CI 0.34-0.48; ≥75 y HR 0.35; 95% CI 0.22-0.54). The results were consistent with the established safety profile of NUBEQA in both age subgroups, with similar incidences of treatment-emergent adverse events versus placebo.

Additionally, a retrospective cohort analysis of adult patients in the U.S. who initiated treatment with androgen receptor pathway inhibitor triplet therapy (either NUBEQA + ADT + DOC [DAR] or abiraterone + ADT + DOC [ABI] found that therapy with NUBEQA in combination with ADT and docetaxel led to lower probability of treatment discontinuation (DAR; 25% [95% CI 0.177-0.334] vs ABI; 38%; 95% CI 0.286-0.484 at 18 months), lower probability of progression to mCRPC (DAR; 24% 95% CI 0.175-0.335 vs ABI; 46% 95% CI 0.358-0.574 at 18 months), and a higher number of patients achieving PSA responses (undetectable level PSA at 12 months; DAR; 61.2% (n=94/141) vs ABI; 46.6% (n=43/102)).

About the ARANOTE Trial⁶

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, 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.

About the ARASENS Trial⁷

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 plus 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 NUBEQA twice a day or matching placebo plus ADT and docetaxel.

The primary endpoint of the trial was OS. Secondary endpoints included time to castration-resistant prostate cancer (CRPC), time to pain progression, time to first symptomatic skeletal event (SSE), and time to initiation of subsequent anticancer therapy, all measured at 12-week intervals, as well as AEs as a measure of safety and tolerability.

About NUBEQA^® (darolutamide)¹

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.^2,8 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.^9,10

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.^11,12,13 Men with metastatic hormone-sensitive prostate cancer (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 metastatic castration-resistant prostate cancer (CRPC), a condition with limited survival.^4,5

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. 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. For more information, go to www.bayer.com.

^© 2025 Bayer
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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. NUBEQA^® (darolutamide) [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; October 2023.
2. 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: January 2025.
3. Ng, K et al. Oncol Ther. 2020;8:209–230.
4. Siegel DA et al. MMWR Morb Mortal Wkly Rep. 2020;69:1473–1480.
5. Hahn AW et al. Am Soc Clin Oncol Educ Book. 2018 May 23;38:363-371.
6. ClinicalTrials.gov NCT04736199. Darolutamide in Addition to ADT Versus ADT in Metastatic Hormone-sensitive Prostate Cancer (ARANOTE). https://www.clinicaltrials.gov/study/NCT04736199. Accessed: January 2025.
7. 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. Accessed: January 2025.
8. Hyuna S et al. Ca Cancer J Clin 2021; 71:209–249.
9. Prostate Cancer: Statistic. Cancer.Net. https://www.cancer.net/cancer-types/prostate-cancer/statistics. September 2024.
10. American Cancer Society. Cancer Facts & Figures 2024. https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/2024-cancer-facts-figures.html. September 2024
11. Piombino C et al. Cancers (Basel). 2023 Oct 11;15(20):4945.
12. Helgstrand JT et al. Cancer. 2018;124(14):2931-2938.
13. Buzzoni C et al. Eur. Urol. 2015;68:885–890.

Contacts

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