Darolutamide Receives FDA Approval for mCSPC

Darolutamide was previously approved in combination with docetaxel for mHSPC.

The FDA has granted approval to darolutamide (Nubeqa) for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC), according to an announcement from the regulatory agency.¹

The efficacy of darolutamide in mHSPC was established by data from the phase 3, randomized, double-blind ARANOTE (NCT02799602) trial. Investigators randomly assigned 669 patients to receive 600 mg of darolutamide, via two 300-mg tablets, twice daily with food, or placebo.²

Additionally, all patients either received standard gonadotropin-releasing androgen deprivation therapy (ADT) or had previously received bilateral orchiectomy.¹

ARANOTE’s primary end point was radiographic progression-free survival (rPFS), as assessed by blinded independent central review, with overall survival (OS) as a secondary end point.

Treatment with darolutamide achieved a 46% reduction in risk of radiographically confirmed progression or death. Researchers identified no statistically significant increase of OS at the final analysis (HR, 0.78; 95% CI, 0.58-1.05).

Patients in the darolutamide arm experienced a statistically significant improvement in rPFS vs the placebo arm and did not reach median rPFS. The placebo arm’s median rPFS was 25 months (95% CI, 19-NR; hazard ratio [HR], 0.54; 95% CI, 0.41-0.71; P < 0.0001).

The FDA recommends a dosage of 600 mg of darolutamide taken twice orally daily with food until disease progression or unacceptable toxicity. The FDA’s announcement also notes that darolutamide’s prescribing information includes warnings for ischemic heart disease, seizure, and embryo-fetal toxicity; in addition, the safety profile of darolutamide reported at the final analysis was consistent with previous findings for darolutamide monotherapy.

Prior Data in mHSPC

The FDA accepted a supplemental new drug application (sNDA) for darolutamide with ADT on November 21 2024.³ The sNDA was based on prior data from ARANOTE presented at the 2024 ESMO Congress.⁴

Data presented at that time was similar, including a 24-month rPFS rate of 70.3% for patients in the experimental arm and 52.1% for patients receiving placebo.

It was reported at that time that the most common treatment-emergent adverse events (TEAEs) associated with darolutamide were fatigue (5.6%), mental impairment disorder (1.6%), hypertension (9.4%), cardiac arrhythmias (8.8%), coronary artery disorders (3.6%), heart failure (0.9%), falls (1.3%), bone fracture (4.0%), vasodilatation and flushing (9.2%), diabetes mellitus and hyperglycemia (9.0%), and rash (4.3%).

“Bayer is dedicated to addressing unmet needs in prostate cancer treatment for various stages of the disease, and today’s acceptance of our sNDA for [darolutamide] plus ADT for the treatment of patients with mHSPC brings us closer to adding an additional treatment option for [darolutamide] to benefit those living with mHSPC,” Christine Roth, executive vice president of Global Product Strategy and Commercialization and member of the Pharmaceuticals Leadership Team at Bayer, stated in a news release. “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. We are working closely with the FDA to bring this additional [darolutamide] treatment option to patients as soon as possible.”

Darolutamide was approved in combination with docetaxel for use in mHSPC on August 22, 2022, based on data from the ARASENS trial (NCT02799602).⁵

At that time, it was reported that AEs occurred in over 10% of patients receiving darolutamide plus docetaxel, most notably decreased appetite, rash, hemorrhage, weight gain, and hypertension.

Additional lab abnormalities occurring for at least 30% of patients receiving the combination were anemia, hyperglycemia, lymphocytopenia, neutropenia, increased AST, increased ALT, and hypocalcemia.

References

1. FDA approves darolutamide for metastatic castration-sensitive prostate cancer. FDA. News release. June 3, 2025. Accessed June 3, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-darolutamide-metastatic-castration-sensitive-prostate-cancer
2. Darolutamide in Addition to Standard Androgen Deprivation Therapy and Docetaxel in Metastatic Hormone-Sensitive Prostate Cancer (ARASENS). ClinicalTrials.Gov. June 15, 2016. Updated April 16, 2024. Accessed June 3, 2025. https://clinicaltrials.gov/study/NCT02799602?id=NCT02799602&rank=1#study-record-dates
3. 1. U.S. FDA accepts supplemental new drug application for Nubeqa (darolutamide) for the treatment of patients with metastatic hormone-sensitive prostate cancer. News release. Bayer. November 21, 2024. Accessed June 3, 2025. https://www.biospace.com/press-releases/u-s-fda-accepts-supplemental-new-drug-application-for-nubeqa-darolutamide-for-the-treatment-of-patients-with-metastatic-hormone-sensitive-prostate-cancer
4. 2. Saad F, Vjaters E, Shore ND, et al. Efficacy and safety of darolutamide plus androgen-deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) from the phase III ARANOTE trial. Ann Oncol. 2024;35(suppl 2):S1257-S1258. doi:10.1016/j.annonc.2024.08.2311
5. FDA approves darolutamide tablets for metastatic hormone-sensitive prostate cancer. FDA. August 5, 2022. Accessed August 5, 2022. https://bit.ly/3SqCCLw