FDA Accepts sNDA for Darolutamide Plus ADT in mHSPC

• The FDA has accepted a supplemental new drug application (sNDA) seeking expanded indication for darolutamide (Nubeqa) for use in combination with androgen deprivation therapy (ADT) for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC).
• Data from the phase 3 ARANOTE trial (NCT04736199) support this sNDA.
• Darolutamide is currently approved by the FDA for use in combination with docetaxel for the treatment of patients with mHSPC and as a monotherapy for patients with nonmetastatic castration-resistant prostate cancer.

The FDA has accepted an sNDA for the combination of darolutamide and ADT for the treatment of patients with mHSPC.¹

The sNDA is supported by findings from the phase 3 ARANOTE trial (NCT04736199). Results from the study presented at the 2024 ESMO Congress showed that there was a 46% reduced risk of radiographic progression or death with darolutamide/ADT compared with placebo plus ADT (HR, 0.54; 95% CI, 0.41-0.71; P <.0001). This met the primary end point of the study.²

At 24 months, the radiologic progression-free survival (rPFS) rates were 70.3% in the darolutamide arm vs 52.1% in the placebo group. The median rPFS was not reached (NR; 95% CI, NR-NR) vs 25.0 months (95% CI, 19.0-NR), respectively.²

There was also benefit with the darolutamide plus ADT combination across all secondary end points, and overall survival (OS) data were immature at the time of the primary analysis.

Darolutamide’s safety profile was consistent with what had been established previously and there were no new safety signals identified with darolutamide plus ADT. Across arms, there was a low incidence of treatment-emergent adverse effects (AEs) and a similar proportion of grade 3 or higher AEs observed.

Darolutamide is currently approved by the FDA in the mHSPC setting for use in combination with docetaxel.

“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,” said Christine Roth, executive vice president, global product strategy and commercialization and member of the Pharmaceuticals Leadership Team at Bayer, in a press release.¹

About the Phase 3 ARANOTE Trial

ARANOTE is a randomized, double-blind, placebo-controlled trial where experts sought to evaluate the safety and efficacy of darolutamide plus ADT vs placebo plus ADT in patients with mHSPC.³

Patients with histologically or cytologically confirmed prostate adenocarcinoma, metastatic disease, an ECOG performance status of 0 to 2, and adequate bone marrow, liver, and renal functions were eligible for enrollment in the study. Further, patients must have started ADT with or without first-generation antiandrogen, but not earlier than 12 weeks prior to randomization.

Once enrolled, patients were randomly assigned in a 2:1 fashion to receive either darolutamide at 600 mg twice daily given with ADT (n = 446) or placebo in combination with ADT (n = 223).

The primary end point of the study was rPFS, which was measured as time from randomization to the date of first documentation of radiological disease progression or death due to any cause. Secondary end points evaluated in the study included OS, time from randomization to the date of first 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.

In addition to the ARANOTE trial, darolutamide is currently being evaluated in the phase 3 ARASTEP trial (NCT05794906) in combination with ADT for the treatment of patients with high-risk biochemical recurrence HSPC with no metastatic disease detected by conventional imaging, and a positive prostate-specific maturation antigen PET/CT scan at baseline, and the phase 3 DASL-HiCaP study (ANZUP1801) of adjuvant darolutamide for the potential treatment of patients with localized prostate cancer with a high risk of recurrence. The DASL-HiCaP study is being led by the Australian and New Zealand Urogenital and Prostate Cancer Trials Group.¹

REFERENCES:

1. U.S. FDA Accepts Supplemental New Drug Application for NUBEQA® (darolutamide) for the Treatment of Patients with Metastatic Hormone-Sensitive Prostate Cancer. Published online and accessed November 21, 2024. https://tinyurl.com/yc44hvwc

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):1-72. doi:10.1016/annonc/annonc1623

3. Darolutamide in addition to ADT versus ADT in metastatic hormone-sensitive prostate cancer (ARANOTE). ClinicalTrials.gov. Updated September 24, 2024. Accessed September 24, 2024. https://clinicaltrials.gov/study/NCT04736199