Docetaxel

The ARANOTE readout could help Nubeqa move closer to Bayer’s target of over 3 billion euros in peak sales. (Bayer) Bayer has claimed a second pivotal trial win for its blockbuster-to-be androgen receptor inhibitor Nubeqa, looking to reach the entire space of metastatic hormone-sensitive prostate cancer (mHSPC). The positive readout, from the phase 3 ARANOTE trial, showed that Nubeqa’s combination with androgen deprivation therapy (ADT) significantly extended the time before tumor progression or death compared with ADT alone, Bayer said Wednesday. The German pharma now plans to submit these data for potential approvals around the world.  The ARANOTE readout could help Nubeqa move closer to Bayer’s target of over 3 billion euros in peak sales. With 869 million euros in sales and an 86.5% growth rate in 2023, Nubeqa is on track to cross the blockbuster bar this year. mHSPC is already contributing to Nubeqa’s sales thanks to an FDA approval in 2022. At that time the phase 3 ARASENS trial showed that the combination of Nubeqa, ADT and the chemotherapy docetaxel lowered the risk of death by 32% versus ADT and chemo. But not all patients can tolerate chemo. For patients with low-volume metachronous metastases, the current National Comprehensive Cancer Network (NCCN) guidelines only recommend ADT in combination with one of three hormone therapies without chemo as the preferred regimens. Overall survival is a secondary endpoint in the current ARANOTE trial. Bayer in its Wednesday announcement didn’t touch on what that data point looks like. The safety profiles were comparable between the two treatment arms, the company said. Besides tumor-slowing or life-extending efficacy, better tolerability has been an important selling point for Nubeqa. In a real-world study called DEAR based on medical records of 828 patients with non-metastatic castration-resistant prostate cancer—which was Nubeqa’s initial indication gained in 2019—patients who took Nubeqa experienced a lower adverse event rate compared with those who got Pfizer and Astellas’ Xtandi or Johnson & Johnson’s Erleada. Treatment discontinuation or progression to metastatic disease also occurred at a lower rate with Nubeqa compared with the other two second-generation androgen receptor inhibitors. In addition to the two existing tumor settings, Bayer is running the phase 3 ARASTEP trial to evaluate whether the addition of Nubeqa could improve on ADT in nonmetastatic hormone-sensitive prostate cancer with high-risk biochemical recurrence. That study could take some time to read out, with an estimated primary completion date in early 2027. With an FDA go-ahead in November, Pfizer and Astellas’ Xtandi, first approved 12 years ago, has already become the first androgen receptor inhibitor to reach that earlier prostate cancer treatment setting. On Bayer’s part, Nubeqa and the kidney disease drug Kerendia are considered key growth drivers for the company’s pharma unit. Two of Bayer’s top-selling drugs are facing major headwinds. The J&J-partnered blood thinner Xarelto has lost patent protection in Bayer’s territories outside the U.S., and the Regeneron-partnered eye med Eylea faces tough competition from Roche’s Vabysmo.  

WHIPPANY, NJ, USA I July 17, 2024 I The Phase III ARANOTE trial, investigating NUBEQA ® (darolutamide) plus androgen deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC), has met its primary endpoint of radiological progression-free survival (rPFS). NUBEQA plus ADT demonstrated a statistically significant and clinically meaningful increase in rPFS compared to placebo plus ADT. Results were consistent with NUBEQA’s established safety profile with no new signals observed. Detailed results from this randomized, double-blind, placebo-controlled trial are planned to be presented at a forthcoming scientific congress. NUBEQA is currently indicated in the U.S. for the treatment of adult patients with mHSPC in combination with docetaxel and for the treatment of adult patients with non-metastatic castration-resistant prostate cancer (nmCRPC). 1 “We are excited to share the positive results from this Phase III trial. Following potential regulatory approval, physicians will be able to tailor NUBEQA treatment plans with or without docetaxel based on individual patient’s needs,” said Christian Rommel, Ph.D., Head of Research and Development at Bayer’s Pharmaceuticals Division. “Today’s results build on the established efficacy and tolerability profile of NUBEQA. We are looking forward to future outcomes of our clinical development program investigating the compound across multiple prostate cancer stages and indications.” Bayer plans to present the pivotal data at a forthcoming scientific conference and discuss these data with the U.S. FDA regarding submission for regulatory approval. About the ARANOTE Trial The ARANOTE trial (NCT04736199) is a randomized, double-blind, placebo-controlled Phase III study designed to assess the efficacy and safety of NUBEQA plus androgen deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). 669 patients were randomized to receive 600mg of NUBEQA twice daily or matching placebo in addition to ADT. 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. Secondary endpoints include overall survival, time from randomization to the date of death from any cause, time from randomization to the date of first castration-resistant event, time to initiation of subsequent anti-cancer therapy, time to prostate-specific antigen (PSA) progression, PSA undetectable rates, time to pain progression, and safety assessments. About NUBEQA ® (darolutamide) 1 NUBEQA ® (darolutamide) is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription. NUBEQA is being evaluated in a robust clinical development program, which includes studies across various stages of prostate cancer, including in the Phase III ARANOTE trial evaluating NUBEQA plus androgen deprivation therapy (ADT) versus ADT alone for mHSPC, the ARASTEP Phase III trial evaluating NUBEQA plus ADT versus ADT alone in HSPC patients with high-risk biochemical recurrence (BCR) and no evidence of metastatic disease by conventional imaging and a positive PSMA PET/CT at baseline, as well as in the Australian and New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) led international Phase III co-operative group DASL-HiCaP (ANZUP1801) trial evaluating NUBEQA 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. NUBEQA is currently indicated in the U.S. in combination with docetaxel and ADT for the treatment of adult patients with mHSPC and for the treatment of adult patients with non-metastatic castration-resistant prostate cancer (nmCRPC) with ADT. 1 NUBEQA is developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company. INDICATIONS NUBEQA ® (darolutamide) is an androgen receptor inhibitor indicated for the treatment of adult patients with: 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 common cancer in men and the fifth most common cause of cancer death in men worldwide. 2 In 2020, an estimated 1.4 million men were diagnosed with prostate cancer, including almost 300,000 cases in the U.S., and about 375,000 died from the disease worldwide. 3,4 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. Upon relapse when the disease will metastasize or spread, androgen deprivation therapy (ADT) is the cornerstone of treatment for this hormone-sensitive disease. Approximately 10% of men will already present with mHSPC when first diagnosed. 5,6,7 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. 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. In line with its mission, “Health for all, Hunger for none,” the company’s 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 2023, the Group employed around 100,000 people and had sales of 47.6 billion euros. R&D expenses before special items amounted to 5.8 billion euros. For more information, go to www.bayer.com . References SOURCE: Bayer