FDA accepts sNDA for darolutamide plus ADT in mHSPC

The FDA has accepted a supplemental new drug application (sNDA) for darolutamide (Nubeqa) in combination with androgen deprivation therapy (ADT) for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC), Bayer announced in a news release.¹

Darolutamide plus ADT significantly extended rPFS vs placebo plus ADT.

Bayer is also seeking approval for this indication in the EU.

Currently, darolutamide is approved in the US for the treatment of adult patients with mHSPC in combination with docetaxel as well as for the treatment of adult patients with non-metastatic castration-resistant prostate cancer.

“Bayer is dedicated to addressing unmet needs in prostate cancer 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 brings us closer to adding an additional treatment option for NUBEQA to benefit those living with mHSPC,” said Christine Roth, Executive Vice President of Global Product Strategy and Commercialization and Member of the Pharmaceuticals Leadership Team at Bayer, in the news release.¹ “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.”

The sNDA is supported by data from the pivotal phase 3 ARANOTE trial (NCT04736199), which were presented earlier this year 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 darolutamide plus ADT 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 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 suggested 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 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, 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 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% were Asian and 9.7% were Black.

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. 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. Published online and accessed November 21, 2024. https://bayer2019tf.q4web.com/news/news-details/2024/U.S.-FDA-Accepts-Supplemental-New-Drug-Application-for-NUBEQA-darolutamide-for-the-Treatment-of-Patients-with-Metastatic-Hormone-Sensitive-Prostate-Cancer/default.aspx

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. 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 and accessed November 21, 2024. https://clinicaltrials.gov/study/NCT04736199