Nubeqa™ (darolutamide) receives EU approval for additional indication in prostate cancer

Berlin, March 1, 2023 – The European Commission has granted marketing authorization in the European Union (EU) for Nubeqa™ (darolutamide), an oral androgen receptor inhibitor (ARi), plus androgen deprivation therapy (ADT) in combination with docetaxel, for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC). Nubeqa is already approved for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease.

“Today’s approval of Nubeqa represents a significant milestone in addressing unmet medical needs for people living with metastatic hormone-sensitive prostate cancer in Europe,” said Christine Roth, Member of the Executive Committee of Bayer’s Pharmaceuticals Division and Head of the Oncology Strategic Business Unit. “We are committed to improving prostate cancer care across all stages of the disease and recognize that for patients and their families, quality of life is just as critical as prolonging survival and delaying disease progression. We continue in our mission to redefine what it means to live with prostate cancer.”

The EU approval is based on the positive results from the Phase III ARASENS trial, which demonstrated that darolutamide plus ADT in combination with docetaxel significantly reduced the risk of death by 32.5% compared to ADT with docetaxel, in patients with mHSPC. Additionally, the darolutamide combination showed consistent benefits across clinically relevant secondary endpoints, with the overall incidence of treatment-emergent adverse events being similar between treatment arms.

“The approval of Nubeqa in mHSPC in Europe is a major step forward for patients and their treating physicians, expanding the treatment options available and our ability to improve clinical outcomes for those living with the disease,” said Prof. Bertrand Tombal, Professor of Urology at the Université catholique de Louvain (UCL), Cliniques universitaires Saint-Luc, Brussels, Belgium. “This approval is supported by robust data from the ARASENS clinical trial, which demonstrate the benefits of darolutamide plus ADT in combination with docetaxel in extending survival, delaying disease progression and maintaining quality of life for patients with metastatic hormone-sensitive prostate cancer.”

Prostate cancer is the most commonly diagnosed cancer in men in almost all northern and western European countries.¹ 

Only 30% of men with mHSPC will survive five years or more after diagnosis.² Most men with mHSPC eventually progress to metastatic castration-resistant prostate cancer (mCRPC), a condition with limited long-term survival.^3,4

 Nubeqa is being investigated in a broad development program with an additional three ongoing or planned large clinical studies, to investigate its potential across prostate cancer patients from the early- to the late-stage of this disease. This includes the ARANOTE Phase III trial evaluating darolutamide and ADT versus ADT alone for mHSPC.

Nubeqa is developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company. Bayer is responsible for global commercialization, with co-promotion from Bayer and Orion Corporation in certain European markets, e.g. France, Germany, Italy, Spain, the UK, Scandinavia and Finland.

About the ARASENS Trial
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, plus ADT in combination with docetaxel to ADT plus docetaxel (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, plus ADT in combination with 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 evaluated at 12‐week intervals, as well as adverse events (AEs) as a measure of safety and tolerability. Results from this trial were published in the New England Journal of Medicine.⁵ A plain language summary publication of these data was published in Future Oncology.⁶ The ARASENS trial demonstrated that darolutamide plus ADT in combination with docetaxel significantly reduced the risk of death by 32.5% compared to ADT with docetaxel alone.⁵ Improvements in the secondary endpoints supported the benefit observed in the primary endpoint, overall survival.⁵

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.⁷

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, or if the disease is newly diagnosed, but has already 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 ADT and docetaxel. 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)
Nubeqa™ (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. This is supported by 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.⁸

The product is approved in more than 80 countries 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. It is also approved for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC) in a number of markets including the U.S and Japan. Filings in other regions are underway or planned. Bayer expects the peak sales potential for Nubeqa to exceed €3 billion. 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 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. In addition, a study to explore the potential of darolutamide in the early setting for patients who have experienced a rise in their prostate specific antigen (PSA) levels following surgery or radiation, is also planned.

About Prostate Cancer at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The company has the passion and determination to develop new medicines that help improve and extend the lives of people living with cancer. Prostate cancer is the second most commonly diagnosed cancer in men⁷ and a key area of focus for Bayer. The company’s franchise includes two products on the market (Nubeqa™ and Xofigo™) and several compounds in development, including a unique approach of advancing targeted alpha therapies. Bayer is focused on addressing the unique needs of prostate cancer patients, providing treatments that extend their lives throughout the different stages of the disease and allowing them to continue their everyday activities, so that they can live longer, better lives.

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 2022, the Group employed around 101,000 people and had sales of 50.7 billion euros. R&D expenses before special items amounted to 6.2 billion euros. For more information, go to www.bayer.com.

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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.       The Cancer Atlas: Europe. 2018. https://canceratlas.cancer.org/the-burden/europe/https://canceratlas.cancer.org/the-burden/europe/. Accessed December 2022. 

2.       Ng, K., Smith, S., Shamash, J. Metastatic Hormone-Sensitive Prostate Cancer (mHSPC): Advances and Treatment Strategies in the First-Line Setting. Oncol Ther. 2020;8:209–230. https://doi.org/10.1007/s40487-020-00119-z.

3.       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.

4.       Hahn AW, Higano CS, Taplin ME, Ryan CJ, Agarwal N. Metastatic Castration-Sensitive Prostate Cancer: Optimizing Patient Selection and Treatment. Am Soc Clin Oncol Educ Book. 2018 May 23;38:363-371. https://doi.org/10.1200/edbk_200967.

5.       Smith M., Hussain M., Saad F. et al. Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer. N Engl J Med. 2022; 386:1132–1142.

6.       Smith M., Hussain M., Saad F. et al. Darolutamide and survival in metastatic, hormone-sensitive prostate cancer: a patient and caregiver perspective and plain language summary of the ARASENS trial. Future Oncol. 2022;18:21:2585-2597. https://doi.org/10.2217/fon-2022-0433

7.       Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries. CA: Cancer J Clin. 2021;71:209–249. https://acsjournals.onlinelibrary.wiley.com/doi/epdf/10.3322/caac.21660. Accessed December 2022.

8.       Colomba E. et al. ODENZA: A French prospective, randomized, open-label, multicenter, cross-over phase II trial of preference between darolutamide and enzalutamide in men with asymptomatic or mildly symptomatic metastatic castrate-resistant prostate cancer (CRPC). J Clin Onc 2021; 39 (15_suppl): 5046-5046.