About the Trial
Trial Name: Darolutamide in Addition to ADT Versus ADT in Metastatic Hormone-sensitive Prostate Cancer (ARANOTE)
ClinicalTrials.gov ID: NCT04736199
Sponsor: Bayer
Completion Date (Estimated): September 26, 2025
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FDA Accepts sNDA for Darolutamide With ADT for Patients With mHSPC
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Key Takeaways
- Darolutamide, an androgen receptor inhibitor, shows significant efficacy in metastatic hormone-sensitive prostate cancer when combined with androgen deprivation therapy.
- The ARANOTE trial demonstrated a 46% reduction in radiological progression or death risk with darolutamide compared to placebo.
The supplemental new drug application (sNDA) is based on results from a phase 3 trial that enrolled patients with metastatic hormone-sensitive prostate cancer (mHSPC).
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The FDA has accepted a supplemental new drug application (sNDA) for darolutamide (Nubeqa; Bayer HealthCare Pharmaceuticals) in combination with an androgen deprivation therapy (ADT) for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC). The sNDA is based on positive results from the phase 3 ARANOTE trial (NCT04736199).1
Darolutamide is an androgen receptor (AR) inhibitor with a chemical structure that specifically and competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription. Darolutamide is indicated for the treatment of adult patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and mHSPC in combination with docetaxel.1
The ARANOTE trial is a randomized, double-blind, placebo-controlled phase 3 trial that evaluated the efficacy and safety of daraolutamide plus ADT in patients with mHSPC. A total of 669 patients were randomly assigned to receive either 600 mg of darolutamide twice per day (n = 446) or a matching placebo (n = 223), both of which were administered with an ADT.1-3
The study’s primary end point is radiological progression-free survival (rPFS), which is measured as time from the date of randomization to the date of first documentation of radiological disease progression or death of any cause, which was assessed at up to 36 months. Secondary end points include overall survival (OS), 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, all of which are assessed at up to 55 months.1,2
According to an analysis at the primary cutoff date (June 7, 2024), darolutamide with ADT had significantly improved rPFS and reduced the risk of radiological progression or death by about 46%, compared with placebo (HR, 0.54 [95% CI, 0.41 to 0.71]; P < .0001). Additionally, there were consistent benefits shown across subgroups, including those with high- and low-volume disease. OS was shown to be in favor of darolutamide compared with placebo (HR, 0.81 [95% CI, 0.59 to 1.12]), with clinical benefits observed across all other secondary end points including delayed time to metastatic castration-resistant prostate cancer (HR, 0.40 [95% CI, 0.32 to 0.51]) and time to pain progression (HR, 0.72 [95% CI, 0.54 to 0.96]).3
In this analysis, adverse events (AEs) were observed to be similar across the 2 groups. Fatigue was less frequent in those receiving darolutamide (5.6%) compared with placebo (8.1%). Fewer patients receiving darolutamide discontinued treatment because of AEs (6.1% vs 9.0%).3
According to the investigators, the analysis findings are consistent with prior studies that evaluated darolutamide with ADT in the nmCRPC setting. A phase 3 trial, ARAMIS (NCT02200614), which was a large real-world cohort study, showed the rate of discontinuation was much lower in those who received darolutamide compared with enzalutamide (Xtandi; Pfizer, Astellas Pharma) and apalutamide (Erleada; Janssen Biotech).3
“If approved, this would expand the indication for [darolutamide] in patients with mHSPC to include [darolutamide] both with and without chemotherapy, providing physicians and their patients with an additional [darolutamide] treatment option in this setting,” said Christine Roth, executive vice president, Global Product Strategy and Commercialization, and member of the Pharmaceuticals Leadership Team at Bayer, in a news release. “We are working closely with the FDA to bring this additional [darolutamide] treatment option to patients as soon as possible.”1
REFERENCES
Bayer. U.S. FDA Accepts Supplemental New Drug Application for NUBEQA® (darolutamide) for the Treatment of Patients with Metastatic Hormone-Sensitive Prostate Cancer. News release. November 21, 2024. Accessed November 21, 2024. https://bayer2019tf.q4web.com/news/news-details/2024/U.S.-FDA-Accepts-Supplemental-New-Drug-Application-for-NUBEQA-darolutamide-for-the-Treatment-of-Patients-with-Metastatic-Hormone-Sensitive-Prostate-Cancer/default.aspx
Darolutamide in Addition to ADT Versus ADT in Metastatic Hormone-sensitive Prostate Cancer (ARANOTE). ClinicalTrials.gov identifier: NCT04736199. Updated November 21, 2024. Accessed November 21, 2024. https://clinicaltrials.gov/study/NCT04736199
Saad F, Vjaters E, Shore N, et al. Darolutamide in Combination With Androgen-Deprivation Therapy in Patients With Metastatic Hormone-Sensitive Prostate Cancer From the Phase III ARANOTE Trial. JCO. 0, JCO-24-01798. doi:10.1200/JCO-24-01798
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