FDA Accepts sNDA for Darolutamide Plus ADT in Metastatic Hormone-Sensitive Prostate Cancer
Key Insights
The FDA has accepted a supplemental new drug application (sNDA) for darolutamide (Nubeqa) in combination with androgen deprivation therapy (search) (ADT) for metastatic hormone-sensitive prostate cancer (search) (mHSPC (search)).
The sNDA is supported by data from the pivotal Phase 3 ARANOTE trial, which demonstrated a significant extension in radiological progression-free survival (rPFS) compared to placebo plus ADT.
Darolutamide plus ADT showed a 46% reduction in the risk of radiological progression or death (HR, 0.54; 95% CI, 0.41-0.71; P < .0001) at 24 months.
The FDA has accepted a supplemental new drug application (sNDA) for darolutamide (Nubeqa) in combination with androgen deprivation therapy (search) (ADT) for the treatment of patients with metastatic hormone-sensitive prostate cancer (search) (mHSPC (search)), Bayer announced. This decision brings darolutamide closer to becoming an additional treatment option for individuals living with mHSPC.
The sNDA is based on data from the Phase 3 ARANOTE trial (NCT04736199), which were presented at the 2024 European Society for Medical Oncology Congress and published in The Journal of Clinical Oncology. The trial evaluated the efficacy and safety of darolutamide plus ADT versus placebo plus ADT in patients with mHSPC (search).
ARANOTE Trial Results
The ARANOTE trial demonstrated that darolutamide plus ADT significantly extended radiological progression-free survival (rPFS) compared with placebo plus ADT. At 24 months, the rPFS rate was 70.3% in the darolutamide arm versus 52.1% in the placebo arm, representing a 46% reduction in the risk of radiological progression or death (HR, 0.54; 95% CI, 0.41-0.71; P < .0001). The median rPFS was not reached in the darolutamide arm, compared with 25.0 months in the placebo arm.
Subgroup analyses indicated that all patient subgroups benefited from treatment with darolutamide plus ADT. For patients with high-volume disease, the hazard ratio (HR) was 0.60 (95% CI, 0.44-0.80), while for those with low-volume disease, the HR was 0.30 (0.15-0.60).
Overall survival (OS) results also suggested a clinical benefit from darolutamide plus ADT. At 24 months, the OS rate was 79.8% in the darolutamide arm and 75.5% in the placebo arm.
Darolutamide was associated with a trend toward clinical benefit in the secondary endpoints of time to metastatic castration-resistant prostate cancer (search) (HR, 0.40; 95% CI, 0.32 to 0.51) and time to prostate-specific antigen (PSA) progression (HR, 0.31; 95% CI, 0.23 to 0.41). Additionally, 62.6% of patients in the darolutamide arm achieved a PSA level less than 0.2 ng/mL at any point during the treatment period, compared with 18.5% of patients in the placebo arm.
Time to pain progression (HR, 0.72; 95% CI, 0.54 to 0.96) and time to subsequent systemic anticancer therapy (HR, 0.40; 95% CI, 0.29 to 0.56) were also delayed in the darolutamide arm.
Safety and Tolerability
The combination of darolutamide and ADT was well-tolerated across both study arms. The incidence of treatment-emergent adverse events (TEAEs) was similar between the two groups, with TEAEs leading to permanent discontinuation of the study drug occurring in 6.1% of patients in the darolutamide arm and 9.0% of patients in the placebo/ADT arm. No new safety signals emerged.
Trial Design
The double-blind, global ARANOTE trial included 669 patients who were randomly assigned 2:1 to receive 600 mg darolutamide twice daily plus ADT (n = 446) or to matching placebo plus ADT (n = 223). The median age of participants was 70 years. Among all participants, 31% were Asian and 9.7% were Black.
The primary endpoint for the trial was rPFS. Secondary endpoints included OS, time to castration-resistant prostate cancer (search), time to PSA progression, time to pain progression, time to subsequent systemic anticancer therapy, and safety.
The trial remains ongoing, with final study completion anticipated for September 2025.
Christine Roth, Executive Vice President of Global Product Strategy and Commercialization and Member of the Pharmaceuticals Leadership Team at Bayer, stated, "Bayer is dedicated to addressing unmet needs in prostate cancer (search) treatment for various stages of the disease, and today’s acceptance of our sNDA application for NUBEQA plus ADT for the treatment of patients with mHSPC (search) brings us closer to adding an additional treatment option for NUBEQA to benefit those living with mHSPC. If approved, this would expand the indication for NUBEQA in patients with mHSPC to include NUBEQA both with and without chemotherapy, providing physicians and their patients with an additional NUBEQA treatment option in this setting. We are working closely with the FDA to bring this additional NUBEQA treatment option to patients as soon as possible."