Positive Results from Phase III Investigational Trial Shows NUBEQA® (darolutamide) Plus Androgen Deprivation Therapy (ADT) and Docetaxel Significantly Increases Overall Survival (OS) in Patients with mHSPC

• NUBEQA plus androgen deprivation therapy (ADT) and docetaxel showed a statistically significant increase in overall survival (OS) with a reduction in the risk of death by 32.5% compared to ADT plus docetaxel (HR=0.68, 95% CI 0.57-0.80; P<0.001) in patients with metastatic hormone-sensitive prostate cancer (mHSPC)¹
• NUBEQA plus ADT and docetaxel also showed a statistically significant benefit across multiple secondary endpoints, including delay in time to castration-resistant prostate cancer (CRPC), time to pain progression, time to first symptomatic skeletal event (SSE) and time to initiation of subsequent systemic antineoplastic therapy¹
• Incidence of treatment-emergent adverse events (TEAEs) was similar for NUBEQA plus ADT and docetaxel and ADT plus docetaxel¹
• First results from the investigational Phase III ARASENS trial selected for oral presentation at the 2022 ASCO GU Cancers Symposium and simultaneously published in The New England Journal of Medicine¹ 

Abstract: 13

Results from the investigational Phase III ARASENS trial have shown that the use of oral androgen receptor inhibitor (ARi) NUBEQA^® (darolutamide) plus androgen deprivation therapy (ADT) and docetaxel significantly increased overall survival (OS) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) compared to ADT plus docetaxel. NUBEQA plus ADT and docetaxel significantly reduced the risk of death by 32.5% compared to ADT plus docetaxel (HR=0.68, 95% CI 0.57-0.80; P<0.001). At the data cutoff date for the primary analysis (October 25, 2021), the median treatment duration was longer for NUBEQA plus ADT and docetaxel (41.0 months) versus ADT plus docetaxel (16.7 months).¹ NUBEQA is currently indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC).

These results were presented at the 2022 ASCO GU Cancers Symposium and simultaneously published in The New England Journal of Medicine.¹

“Metastatic prostate cancer is a uniformly fatal disease and despite progress in recent years, only 30% of these men will survive beyond five years. ARASENS demonstrated that the addition of NUBEQA, an androgen receptor inhibitor, significantly increased overall survival for patients receiving standard androgen deprivation therapy and docetaxel as initial treatment for metastatic hormone-sensitive prostate cancer. NUBEQA also improved time to castration-resistant prostate cancer and other key secondary endpoints,” said Matthew Smith, M.D., Ph.D., Director of the Genitourinary Malignancies Program, Massachusetts General Hospital Cancer Center. “These results are an important step forward for the treatment of patients with metastatic hormone-sensitive prostate cancer.”

“With the ARASENS results in mHSPC adding to the existing Phase III ARAMIS data in nmCRPC, NUBEQA has now shown positive data in two pivotal clinical trials for patients across these key disease stages in prostate cancer,” said Robert LaCaze, Member of the Executive Committee of Bayer’s Pharmaceutical Division and Head of the Oncology SBU at Bayer. “We believe NUBEQA has the potential to become a foundational drug for appropriate prostate cancer patients. We are committed to making this potential new treatment option in mHSPC available to patients and their treating physicians, and therefore are pursuing the fastest possible regulatory timelines.”

ARASENS is the only randomized, double-blind pivotal study prospectively designed to compare the use of a second-generation ARi plus ADT and docetaxel to ADT plus docetaxel (a guideline recommended standard-of-care) in mHSPC.²

Detailed results from ARASENS

The significant improvement in OS was observed despite substantially higher use of subsequent systemic antineoplastic therapies (such as abiraterone, enzalutamide, cabazitaxel, docetaxel, radium-223 dichloride, sipuleucel-T, lutetium-177 PSMA, or apalutamide) among patients receiving ADT plus docetaxel who entered follow-up (75.6%) compared with the group who received NUBEQA plus ADT and docetaxel (56.8%).¹

NUBEQA plus ADT and docetaxel demonstrated statistically significant benefits across multiple secondary endpoints compared to ADT plus docetaxel, including delaying the time to castration-resistant prostate cancer (CRPC) (HR=0.36, 95% CI 0.30-0.42; P<0.001), time to pain progression (HR=0.79, 95% CI 0.66-0.95; P=0.01), time to first symptomatic skeletal event (SSE) (HR=0.71, 95% CI 0.54-0.94; P=0.02) and time to initiation of subsequent systemic antineoplastic therapy (HR=0.39, 95% CI 0.33-0.46; P<0.001).¹

Treatment-emergent adverse events (TEAEs) were similar between treatment arms. The most common TEAEs (≥10%) were highest during the overlapping docetaxel treatment period for both arms and decreased progressively thereafter. The most frequently reported AEs in the treatment arms (NUBEQA plus ADT and docetaxel versus ADT plus docetaxel) were alopecia (40.5% and 40.6%, respectively), neutropenia (39.3% and 38.8%, respectively), fatigue (33.1% and 32.9%, respectively) and anemia (27.8% and 25.1%, respectively). Grade 3 or 4 AEs reported in 66.1% versus 63.5% of patients were mainly due to neutropenia (33.7% versus 34.2%, respectively). Serious AEs occurred in 44.8% versus 42.3% of patients, and TEAEs leading to treatment discontinuation occurred in 13.5% versus 10.6% of patients.¹

AEs of special interest in patients treated with AR pathway inhibitors for prostate cancer such as fatigue, falls, fractures, mental impairment and cardiovascular events were similar between study arms.¹

About the ARASENS Trial²

The ARASENS trial (NCT02799602) is a randomized, Phase III, multi-center, double-blind, placebo-controlled trial which was prospectively designed to investigate the efficacy and safety of oral NUBEQA, an androgen receptor inhibitor (ARi), plus androgen deprivation therapy (ADT) and the chemotherapy 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 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 NUBEQA^® (darolutamide)³

NUBEQA is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription.³

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.³ 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.³ 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.⁴

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.^5,6 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, most men with mHSPC will eventually progress to metastatic castration-resistant prostate cancer (mCRPC), a condition with limited survival.^7,8

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.

^© 2022 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.

References

1. Smith M., Hussain M., Saad F. et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022.
2. 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.
3. NUBEQA^® (darolutamide) tablets [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, January 2021.
4. 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 February 2022.
5. Cancer.Net 2020: Prostate Cancer Statistics. https://www.cancer.net/cancer-types/prostate-cancer/statistics. Accessed February 2022.
6. American Cancer Society: Hormone Therapy for Prostate Cancer. https://www.cancer.org/cancer/prostate-cancer/treating/hormone-therapy.html. Accessed February 2022.
7. 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.
8. 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.

PP-NUB-US-1545-1 02/22

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