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Darolutamide plus androgen deprivation therapy and docetaxel demonstrates consistent overall survival benefits across various patient segments in metastatic hormone-sensitive prostate cancer


New subgroup analysis from Phase III ARASENS trial in patients with metastatic hormone-sensitive prostate cancer (mHSPC), shows that darolutamide plus androgen deprivation therapy (ADT) and docetaxel provides consistently favorable overall survival (OS) benefits across patient subgroups with various types of metastatic disease, compared to placebo plus ADT and docetaxel(1) / Adverse event (AE) rates were similar in both treatment arms

Not intended for U.S. and UK Media - New late-breaking data from Phase III ARASENS trial presented in the Game Changer oral session at the European Association of Urology Congress 2022 (EAU22)

Berlin, July 4, 2022 - New late-breaking data from the pivotal Phase III ARASENS trial confirm consistent overall survival (OS) benefits of darolutamide plus androgen deprivation therapy (ADT) and docetaxel in patients with metastatic hormone-sensitive prostate cancer (mHSPC), in pre-specified subgroups based on extent of metastatic spread (bone or visceral metastases) and alkaline phosphatase (ALP) value (< or ≥ upper limit of normal [ULN] at study entry), compared to a current standard of care, ADT plus docetaxel.1 Adverse event (AE) rates were similar in both treatment arms. 

Of the 1,306 mHSPC patients who were randomized, 79.5% had bone metastases (M1b) and 17.5% had visceral metastases (M1c); 55.5% had ALP ≥ ULN. Extent of metastatic spread and ALP value are known prognostic factors in patients with mHSPC. 

"These latest results from the ARASENS trial reaffirm the overall survival benefits of darolutamide plus ADT and docetaxel across various patient segments in mHSPC, and provide treating physicians with further detail on those who may benefit from this therapy as it becomes available," said Karim Fizazi M.D., Ph.D., Professor of Medicine at the Institute Gustave Roussy, Villejuif, France.

In the ARASENS trial, 1,306 patients were randomized 1:1 to receive darolutamide plus ADT and docetaxel or placebo plus ADT and docetaxel. Randomization was stratified by metastatic spread according to the most widely used cancer staging system, TNM (tumor, node, metastasis) classification: non-regional lymph node metastases only [M1a]; bone plus or minus lymph node metastases [M1b]; visceral plus or minus lymph node/bone metastases [M1c] and ALP value (< or ≥ ULN at study entry).

A consistent OS benefit was seen across the pre-specified subgroups with darolutamide plus ADT and docetaxel compared to ADT plus docetaxel, with a reduction in risk of death of 33% for subgroup M1b (hazard ratio [HR]=0.66, 95% CI 0.54-0.80) and 21% for M1c (HR=0.76, 95% CI 0.53-1.10). Subgroup M1a (n=39) was too small for meaningful comparison. For patients with ALP <ULN, reduction in risk of death was 36% (HR=0.65, 95% CI 0.47–0.89) and 31% for patients with ALP ≥ULN (HR=0.69, 95% CI 0.56–0.85).

These results add to existing data from the overall population in the ARASENS trial showing that darolutamide plus ADT and docetaxel significantly reduced the risk of death in patients with mHSPC by 32.5% (HR 0.68; 95% CI 0.57-0.80; P<0.001) compared to ADT plus docetaxel. 

Safety analyses showed that the rates of any-grade, grade 3-5, and serious AEs were similar for both arms in the overall population. The incidences of the most common treatment-emergent AEs (≥10%), the majority of which are known docetaxel-related AEs, were highest during the overlapping docetaxel treatment period in both arms.

"These favorable data from ARASENS in mHSPC, along with the ARAMIS data in non-metastatic castration-resistant prostate cancer (nmCRPC), reinforce the potential for darolutamide to be an optimal hormone therapy for eligible prostate cancer patients globally," said Tara Frenkl, MD, MPH, Head of Oncology Development, Oncology Strategic Business Unit, Bayer. "We look forward to building on this body of evidence with future analyses from darolutamide’s clinical development program in metastatic hormone-sensitive prostate cancer." 

Darolutamide is developed jointly by Bayer and Orion Corporation, a globally operating Finnish Pharmaceutical company.

About the ARASENS Trial2
The ARASENS trial is the only randomized, Phase III, multi-center, double-blind, trial which was prospectively designed to compare the use of a second-generation oral androgen receptor inhibitor (ARi) darolutamide in combination with docetaxel plus androgen deprivation therapy (ADT) to docetaxel plus ADT (a guideline recommended standard-of-care) in 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 darolutamide twice a day or matching placebo, in combination with docetaxel plus ADT.

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 evaluated at 12‐week intervals, as well as adverse events (AEs) as a measure of safety and tolerability.

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 worldwide3

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, the disease is hormone-sensitive and androgen deprivation therapy (ADT) is the cornerstone of treatment. 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 docetaxel chemotherapy and ADT. Despite these treatments, a large proportion of men with mHSPC will eventually experience progression to metastatic castration-resistant prostate cancer (mCRPC), a condition with high morbidity and limited survival.

About Nubeqa™ (darolutamide)
Darolutamide is an oral androgen receptor inhibitor (ARi) with a distinct chemical structure that binds to the receptor with high affinity and exhibits strong antagonistic activity, thereby inhibiting the receptor function and the growth of prostate cancer cells. The low potential for blood-brain barrier penetration for darolutamide is supported by preclinical models and neuroimaging data in healthy humans. A low blood-brain barrier penetration would explain the overall low incidence of central nervous system (CNS)-related adverse events (AEs) compared to placebo as seen in the ARAMIS Phase III trial and the improved verbal learning and memory observed in the darolutamide arm of the Phase II ODENZA trial. 

The product is approved under the brand name Nubeqa™ in more than 60 markets around the world, including the U.S., EU, Japan and China for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease. The compound is also being investigated in further studies across various stages of prostate cancer, including in the ARANOTE Phase III trial evaluating darolutamide plus androgen deprivation therapy (ADT) versus ADT alone for metastatic hormone-sensitive prostate cancer (mHSPC), as well as the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) led international Phase III co-operative group DASL-HiCaP (ANZUP1801) trial evaluating darolutamide as an adjuvant treatment for localized prostate cancer with very high risk of recurrence. Information about these trials can be found at www.clinicaltrials.gov.

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 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 2021, the Group employed around 100,000 people and had sales of 44.1 billion euros. R&D expenses before special items amounted to 5.3 billion euros. For more information, go to www.bayer.com.

1 Bertrand T et al, Overall Survival with Darolutamide Versus Placebo in Combination with Androgen-Deprivation Therapy and Docetaxel by Stratification Factors in the Phase 3 ARASENS Trial. Presented at EAU22 July 2022 
2 Smith R et al. N Engl J Med 2022; 386:1132-1142
3Global 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 June 2022

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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.



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