Darolutamide sNDA Submitted to FDA and EMA for mHSPC Treatment
Key Insights
Bayer has submitted applications to the FDA and EMA for darolutamide, seeking approval for use in combination with androgen deprivation therapy (search) (ADT) for metastatic hormone-sensitive prostate cancer (search) (mHSPC).
The submissions are based on Phase III ARANOTE trial results, which demonstrated a 46% reduction in the risk of radiological progression or death compared to placebo plus ADT.
Darolutamide, already approved for other prostate cancer (search) indications, could offer a new treatment option for mHSPC patients, regardless of chemotherapy use.
Bayer has announced the submission of a supplemental new drug application (sNDA) to the U.S. Food and Drug Administration (FDA) and an application to the European Medicines Agency (EMA) for darolutamide (Nubeqa™), an oral androgen receptor (search) inhibitor (ARi). The applications seek approval for darolutamide in combination with androgen deprivation therapy (search) (ADT) for the treatment of patients with metastatic hormone-sensitive prostate cancer (search) (mHSPC).
The submissions are based on positive results from the pivotal Phase III ARANOTE trial, which demonstrated a significant reduction in the risk of radiological progression or death with darolutamide plus ADT compared to placebo plus ADT.
ARANOTE Trial Results
The ARANOTE trial, a randomized, double-blind, placebo-controlled study, evaluated the efficacy and safety of darolutamide plus ADT in patients with mHSPC. The trial randomized 669 patients to receive either 600 mg of darolutamide twice daily or a matching placebo, both in addition to ADT.
The primary endpoint of the study was radiological progression-free survival (rPFS), measured as the time from randomization to the first documented radiological disease progression or death from any cause. Secondary endpoints included overall survival (OS), time to 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.
Results from the ARANOTE trial, presented at the 2024 ESMO Congress, showed that darolutamide plus ADT significantly reduced the risk of radiological progression or death by 46% compared to placebo plus ADT (HR 0.54; 95% CI 0.41–0.71; P<0.0001). At 24 months, the rPFS rate was 70.3% in the darolutamide arm versus 52.1% in the placebo arm. Median rPFS was not reached in the darolutamide arm, compared to 25.0 months in the placebo arm.
Consistent benefits in rPFS were observed across pre-specified subgroups, including patients with high- and low-volume mHSPC. Although overall survival (OS) data were immature at the time of the primary analysis, benefits were observed with the darolutamide plus ADT combination across all secondary endpoints.
Safety and Tolerability
The safety profile of darolutamide in the ARANOTE trial was consistent with previous studies. Treatment-emergent adverse events (TEAEs) were low and similar between treatment groups. The incidence of grade 3 or higher AEs was also similar across arms, and no new safety signals were identified with darolutamide plus ADT.
Current Approvals and Future Implications
Darolutamide is currently approved in over 80 markets for mHSPC in combination with ADT and docetaxel. It is also approved in combination with ADT for non-metastatic castration-resistant prostate cancer (search) (nmCRPC) patients at high risk of developing metastatic disease in more than 85 countries.
If approved for this new indication, darolutamide could provide an additional treatment option for mHSPC patients, potentially improving outcomes and quality of life. Christine Roth, Executive Vice President, Global Product Strategy and Commercialization and Member of the Pharmaceuticals Leadership Team at Bayer, stated, “Our ambition is to redefine what it means to live with prostate cancer (search) at different stages of the disease, extending survival and delaying disease progression, while maintaining daily living.”
Ongoing Research
Darolutamide is also being investigated in the Phase III ARASTEP trial for hormone-sensitive high-risk biochemical recurrence prostate cancer (search) and in the Phase III DASL-HiCaP trial as an adjuvant treatment for localized prostate cancer with a high risk of recurrence.