Expanded indication sought for darolutamide in mHSPC in China

Bayer has submitted an application to the Center of Drug Evaluation (CDE) of China’s National Medical Products Administration (NMPA) seeking approval for darolutamide (Nubeqa) in combination with androgen deprivation therapy (ADT) for patients with metastatic hormone-sensitive prostate cancer (mHSPC).¹

Bayer is also seeking approval for the combination in the US and the EU.

If approved, this would mark the third approved prostate cancer indication for darolutamide in China. Darolutamide is currently indicated in combination with ADT and docetaxel for mHSPC, as well as in combination with ADT for the treatment of patients with non-metastatic castration-resistant prostate cancer who are at high risk of progressing to metastatic disease.

Bayer is also currently seeking approval for darolutamide plus ADT without chemotherapy in mHSPC in the US and the EU. The FDA accepted the company’s supplemental new drug application for the indication in November 2024.

Data on darolutamide plus ADT

The applications are supported by data from the pivotal phase 3 ARANOTE trial (NCT04736199), which were presented at the 2024 European Society for Medical Oncology Congress in Barcelona, Spain and concurrently published in The Journal of Clinical Oncology.^2,3

Overall, data from the trial showed that the combination of darolutamide plus ADT without chemotherapy significantly extended radiological progression-free survival (rPFS) compared with placebo plus ADT in patients with mHSPC.

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 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.

According to the authors, all subgroups derived benefit from treatment with darolutamide plus ADT. The hazard ratio (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).

Overall survival (OS) results also trended toward clinical benefit with 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 also 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 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 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, treatment was well-tolerated in 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 emerged.

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. Among all participants, 31.2% were Asian and 9.7% were Black.

The median duration of treatment was 24.2 months in the darolutamide arm and 17.3 months in the placebo arm. Median follow-up was 25.3 months and 25.0 months, respectively.

The primary end point for the trial was rPFS. Secondary end points included OS, time to castration-resistant prostate cancer, 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 2025.⁴

References

1. Orion’s collaboration partner Bayer submits application in China for third indication of darolutamide. News release. Orion Oyj. Published online and accessed January 7, 2024. https://www.orion.fi/en/newsroom/all-news/releases/press-releases/2025/orions-collaboration-partner-bayer-submits-application-in-china-for-third-indication-of-darolutamide/

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. Presented at: 2024 European Society for Medical Oncology Congress. September 13-17, 2024. Barcelona, Spain. Abstract LBA68. https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.esmo/static/esmo2024_abstracts/LBA68.html.pdf

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

4. Darolutamide in addition to ADT versus ADT in metastatic hormone-sensitive prostate cancer (ARANOTE). ClinicalTrials.gov. Last updated December 27, 2024. Accessed January 7, 2024. https://clinicaltrials.gov/study/NCT04736199