NUBEQA® (darolutamide) Impact on Local Symptoms Evaluated in Men with Non-Metastatic Castration-Resistant Prostate Cancer (nmCRPC)

• Post-hoc analysis of the Phase III ARAMIS trial showed NUBEQA^® (darolutamide) was associated with delayed deterioration in patient quality of life (QoL) related to urinary and bowel symptoms in men with non-metastatic castration-resistant prostate cancer (nmCRPC)¹

Presentation: PD34-10

A post-hoc analysis of the Phase III ARAMIS trial presented at the 2021 AUA Annual Meeting assessing NUBEQA^® (darolutamide) in men with non-metastatic castration-resistant prostate cancer (nmCRPC) reinforces the established clinical profile.^1,2 NUBEQA is indicated in the U.S. for the treatment of men with nmCRPC.

Research presented at the meeting found that NUBEQA plus androgen deprivation therapy (ADT) prolonged time to first prostate cancer-related invasive procedures, an exploratory endpoint (HR=0.416; 95% CI, 0.279-0.620), and was associated with a reduction in locally invasive procedures versus ADT alone (4.7% versus 9.6%). In a post-hoc analysis, NUBEQA plus ADT also delayed the time to deterioration in quality of life (QoL) in two of the six subscales of the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC-QLQ-PR25): urinary symptoms (25.8 versus 14.8 months; HR=0.64; 95% CI, 0.54-0.76) and bowel symptoms (18.4 versus 11.5 months; HR=0.78; 95% CI, 0.66-0.92) versus ADT alone.¹

In the Phase III ARAMIS trial primary analysis, serious adverse reactions in ≥ 1% of patients who received NUBEQA included urinary retention, pneumonia, and hematuria.

“Local symptoms from the prostate and surrounding tissues can be very detrimental to patients’ QoL. The occurrence of local symptoms and invasive procedures is very important in initial nmCRPC treatment discussions between patients and physicians,” said Neal Shore, MD, FACS, Medical Director, CPI, Carolina Urologic Research Center. “The results on QoL and invasive procedures reinforce NUBEQA’s value in nmCRPC.”

Data from the Phase III ARAMIS Trial

Previously published results in 1,509 patients from the Phase III ARAMIS trial demonstrated a highly significant improvement in the primary efficacy endpoint of metastasis-free survival (MFS), with a median of 40.4 months (n=955) with NUBEQA plus ADT, compared to 18.4 months (n=554) for placebo plus ADT (p<0.001). MFS is defined as the time from randomization to the time of first evidence of blinded independent central review (BICR)-confirmed distant metastasis or death from any cause within 33 weeks after the last evaluable scan, whichever occurred first.²

The six subscales of the EORTC-QLQ-PR25 are: urinary symptoms, bowel symptoms, hormone treatment-related symptoms, incontinence aid use, sexual activity and sexual functioning.

The proven tolerability of NUBEQA was supported by the three adverse reactions occurring more frequently in the NUBEQA arm (≥2% over placebo): fatigue (16% versus 11%), pain in extremity (6% versus 3%) and rash (3% versus 1%). NUBEQA was not studied in women and there is a warning and precaution for embryo-fetal toxicity.²

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 A Phase III study in metastatic hormone-sensitive prostate cancer (ARASENS) is ongoing. Information about this trial can be found at www.clinicaltrials.gov.

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 Prostate Cancer

Prostate cancer is the second most commonly diagnosed malignancy in men worldwide.³ In 2020, about 192,000 men in the U.S. were diagnosed with prostate cancer and an estimated 33,000 have died from the disease.⁴ Prostate cancer is the fifth leading cause of death from cancer in men.³ Prostate cancer results from the abnormal proliferation of cells within the prostate gland, which is part of a man’s reproductive system.⁵ It mainly affects men over the age of 50, and the risk increases with age.⁶

Treatment options range from surgery to radiation treatment to therapy using hormone-receptor antagonists, i.e., substances that stop the formation of testosterone or prevent its effect at the target location.⁷ However, in nearly all cases, the cancer eventually becomes resistant to conventional hormone therapy.⁸

Castration-resistant prostate cancer (CRPC) is an advanced form of the disease where the cancer keeps progressing even when the amount of testosterone is reduced to very low levels in the body. The field of treatment options for castration-resistant patients is evolving rapidly for CRPC patients who have prostate cancer that has not spread to other parts of the body with rising prostate-specific antigen (PSA) levels despite a castrate testosterone level, which is called non-metastatic castration-resistant prostate cancer, or nmCRPC.^9,10 About one-third of men with nmCRPC go on to develop metastases within two years.¹¹ In men with progressive nmCRPC, a short PSA doubling time is correlated with shortened time to first metastasis and death.¹⁰

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.

References

1. Shore N. et al. Impact of darolutamide on local symptoms in patients with nonmetastatic castration-resistant prostate cancer [abstract]. AUA 2021. Presentation PD34-10.
2. NUBEQA^® (darolutamide) tablets [Prescribing Information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, January 2021.
3. GLOBAL CANCER OBSERVATORY: Prostate Cancer. Cancer Today. http://gco.iarc.fr/today/data/pdf/fact-sheets/cancers/cancer-fact-sheets-19.pdf. Published 2018. Last Accessed August 2021.
4. American Cancer Society. Cancer Facts & Figures 2020. https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/annual-cancer-facts-and-figures/2020/cancer-facts-and-figures-2020.pdf. Accessed August 2021.
5. American Cancer Society. What is Prostate Cancer? https://www.cancer.org/content/dam/CRC/PDF/Public/8793.00.pdf. Accessed August 2021.
6. American Cancer Society. Prostate Cancer Risk Factors. https://www.cancer.org/content/dam/CRC/PDF/Public/8794.00.pdf. Accessed August 2021.
7. National Cancer Institute. Hormone Therapy for Prostate Cancer. https://www.cancer.gov/types/prostate/prostate-hormone-therapy-fact-sheet. Accessed August 2021.
8. Nakazawa, Mary; Paller, Channing; Kyprianou, Natasha. Mechanisms of Therapeutic Resistance in Prostate Cancer. Curr Oncol Rep (2017) 19:13.
9. Mayo Clinic. Prostate cancer screening: Should you get a PSA test?. https://www.mayoclinic.org/tests-procedures/psa-test/in-depth/prostate-cancer/art-20048087. Accessed August 2021.
10. Howard, Lauren; Moreira, Daniel M; DeHoedt, Amanda; Aronson, William J., et al. Thresholds for PSA doubling time in men with non-metastatic castration-resistant prostate cancer. BJU Int 2017;120: E80-E86.
11. Kirby, Mike, Hirst, Ceri, Crawford. E. David. Characterising the castration-resistant prostate cancer population: a systematic review. Int J Clin Pract. 2011;65(11):1180-1192. doi:10.1111/j.1742-1241.2011.02799.

PP-NUB-US-1297-2 9/21

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