Phase III Investigational Trial of NUBEQA® (darolutamide) in Combination with Docetaxel and Androgen Deprivation Therapy (ADT) Meets Primary Endpoint of Significantly Increasing Overall Survival (OS) in Patients with mHSPC

• Phase III ARASENS trial meets primary endpoint of overall survival for NUBEQA in combination with docetaxel and androgen deprivation therapy (ADT) versus docetaxel and ADT, a standard of care in men with metastatic hormone-sensitive prostate cancer (mHSPC)
• Bayer plans to present these pivotal data at a forthcoming scientific congress and discuss them with health authorities
• ARASENS is part of broad development program for NUBEQA, which includes another ongoing Phase III trial in mHSPC, ARANOTE, evaluating NUBEQA plus ADT

 

WHIPPANY, N.J.–(BUSINESS WIRE)–The Phase III ARASENS trial investigating the use of the oral androgen receptor inhibitor (ARi) NUBEQA^® (darolutamide) in metastatic hormone-sensitive prostate cancer (mHSPC) has met its primary endpoint. In the ARASENS trial, NUBEQA in combination with docetaxel and androgen deprivation therapy (ADT) significantly increased overall survival (OS) compared to docetaxel and ADT. The overall incidence of reported adverse events was similar between treatment arms. Detailed results of the study are planned to be presented at an upcoming scientific congress. NUBEQA is currently indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC).

The ARASENS trial investigating NUBEQA is the only Phase III randomized, multi-center, double-blind trial, which was prospectively designed to evaluate the efficacy and safety of a combination of an ARi with docetaxel and ADT compared to docetaxel and ADT in patients with mHSPC.¹

“For patients with mHSPC, there remains a significant need for new therapeutic approaches that improve treatment outcomes. ARASENS was prospectively designed to investigate whether combining NUBEQA with docetaxel and ADT could lead to an increase in overall survival for men with mHSPC,” said Scott Z. Fields, M.D., Senior Vice President and Head of Oncology Development at Bayer’s Pharmaceutical Division. “We are especially grateful to the patients and investigators for participating in this important trial and look forward to presenting the full results at an upcoming meeting.”

Bayer plans to discuss the data from ARASENS with health authorities worldwide regarding the submission of NUBEQA for marketing authorization in this indication.

About the ARASENS Trial¹

The ARASENS trial (NCT02799602) is a randomized, Phase III, multi-center, double-blind, placebo-controlled trial, which was prospectively designed to investigate the safety and efficacy of oral NUBEQA, an androgen receptor inhibitor (ARi), in combination with the chemotherapy docetaxel and androgen deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). 1,306 newly diagnosed patients were randomized in a 1:1 ratio to receive 600 mg of NUBEQA twice a day or matching placebo, in addition to docetaxel and standard ADT.

The primary endpoint of this trial is overall survival (OS). Secondary endpoints include time to castration-resistant prostate cancer (CRPC), time to initiation of subsequent anticancer therapy, time to first symptomatic skeletal event (SSE), time to pain progression, all measured at 12‐week intervals, as well as adverse events as a measure of safety and tolerability.

About the ARANOTE Trial

The ARANOTE trial (NCT04736199) is a randomized, double-blind, placebo-controlled Phase III study of NUBEQA in addition to androgen deprivation therapy (ADT) versus placebo plus ADT in men with metastatic hormone-sensitive prostate cancer (mHSPC). The primary endpoint of this study is radiological progression-free survival (rPFS), as measured as the time from the date of randomization to the date of first documentation of radiological progressive disease or death due to any cause, whichever occurs first.

About NUBEQA^® (darolutamide)²

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

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 or androgen deprivation therapy (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 another Phase III trial in metastatic hormone-sensitive prostate cancer (mHSPC) (ARANOTE) as well as a Phase III trial evaluating NUBEQA as an adjuvant treatment for localized prostate cancer with very high risk of recurrence (DASL-HiCaP). 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 currently indicated for the treatment of men with nmCRPC.² The approvals of NUBEQA 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.² Filings in other regions are underway or planned.

INDICATION FOR NUBEQA^® (darolutamide)

NUBEQA^® (darolutamide) is an androgen receptor inhibitor indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer.

IMPORTANT SAFETY INFORMATION FOR NUBEQA^® (darolutamide)

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

Serious adverse reactions occurred in 25% of patients receiving NUBEQA and in 20% of patients receiving placebo. Serious adverse reactions in ≥1 % of patients who received NUBEQA were urinary retention, pneumonia, and hematuria. Overall, 3.9% of patients receiving NUBEQA and 3.2% of patients receiving placebo died from adverse reactions, which included death (0.4%), cardiac failure (0.3%), cardiac arrest (0.2%), general physical health deterioration (0.2%), and pulmonary embolism (0.2%) for NUBEQA.

Adverse reactions occurring more frequently in the NUBEQA arm (≥2% over placebo) were fatigue (16% vs 11%), pain in extremity (6% vs 3%) and rash (3% vs 1%).

Clinically significant adverse reactions occurring in ≥2% of patients treated with NUBEQA included ischemic heart disease (4.0% vs 3.4% on placebo) and heart failure (2.1% vs 0.9% on placebo).

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 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.³

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.^4,5 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. 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 castration-resistant prostate cancer (CRPC), a condition with limited survival.^6,7

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 2020, the Group employed around 100,000 people and had sales of 41.4 billion euros. R&D expenses before special items amounted to 4.9 billion euros. For more information, go to www.bayer.com.

^© 2021 Bayer

BAYER, the Bayer Cross and NUBEQA are registered trademarks of Bayer.

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.

PP-NUB-US-1407-1

12/21

References

1. 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.

2. NUBEQA^® (darolutamide) tablets [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, January 2021.

3. 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 October 2021.

4. Cancer.Net 2020: Prostate Cancer Statistics. https://www.cancer.net/cancer-types/prostate-cancer/statistics. Accessed October 2021.

5. American Cancer Society: Hormone Therapy for Prostate Cancer. https://www.cancer.org/cancer/prostate-cancer/treating/hormone-therapy.html. Accessed October 2021.

6. 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.

7. 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.

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