CHMP recommends EU approval of darolutamide plus ADT in mHSPC

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending approval of darolutamide (Nubeqa) in combination with androgen deprivation therapy (ADT) for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC), according to a news release from Orion Pharma, who develops darolutamide alongside Bayer.¹

Darolutamide was approved by the FDA for use without docetxel in mHSPC in June 2025.

Darolutamide was approved in this indication in the US in June 2025.² With this approval, darolutamide became the first androgen receptor inhibitor to be FDA approved for use in patients with mHSPC with or without chemotherapy.

The European Commission is expected to make a decision regarding marketing authorization of darolutamide in the EU in the coming months.

Data on darolutamide

The approval is supported by data from the pivotal phase 3 ARANOTE trial (NCT04736199), which showed that darolutamide plus ADT significantly extended radiographic progression-free survival (rPFS) compared with placebo plus ADT in patients with mHSPC.³

At 24 months, the rate of rPFS was 70.3% in the darolutamide arm vs 52.1% in the placebo arm, translating to a 46% reduction in the risk of radiographic 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 (95% CI, 19 to NR) in the placebo arm.

According to the authors, all prespecified subgroups showed a benefit in rPFS from treatment with darolutamide plus ADT. The HR for high-volume disease was 0.60 (95% CI, 0.44-0.80), and the HR for low-volume disease was 0.30 (0.15-0.60).

In a final analysis of the data, there was no statistically significant improvement in overall survival (OS) with the addition of darolutamide (HR, 0.78; 95% CI, 0.58 to 1.05).² At 24 months, the OS rate was 79.8% in the darolutamide arm and 75.5% in the placebo arm.

In total, 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 (range, 43 to 93). Among all participants, 32.3% were Asian and 9.2% were Black.

The primary end point for the trial was rPFS. Secondary end points included OS, time to castration-resistant prostate cancer, time to prostate-specific antigen (PSA) progression, time to pain progression, time to subsequent systemic anticancer therapy, and safety.

Data from the trial, which were published in the Journal of Clinical Oncology,³ also showed improvements in the trial's key secondary end points with the addition of darolutamide.

Specifically, darolutamide was associated with a trend toward clinical benefit in the secondary end points of time to metastatic castration-resistant prostate cancer (HR, 0.40; 95% CI, 0.32 to 0.51) and time to PSA progression (HR, 0.31; 95% CI, 0.23 to 0.41). Additionally, 62.6% of patients in the darolutamide arm achieved a PSA 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.

Regarding safety, the combination was well-tolerated across both study arms. The incidence of treatment-emergent adverse events (TEAEs) was similar between the 2 groups, with TEAEs leading to permanent discontinuation of 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 were reported.

REFERENCES

1. CHMP recommends third indication for darolutamide for patients with advanced prostate cancer. News release. Orion Oyj. Published online and accessed June 20, 2025. https://www.orionpharma.com/newsroom/all-news/releases/press-releases/2025/chmp-recommends-third-indication-for-darolutamide-for-patients-with-advanced-prostate-cancer/

2. FDA approves darolutamide for metastatic castration-sensitive prostate cancer. News release. US Food & Drug Administration. June 3, 2025. Accessed June 20, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-darolutamide-metastatic-castration-sensitive-prostate-cancer

3. 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. J Clin Oncol. 2024 Sep 16:JCO2401798. doi:10.1200/JCO-24-01798