sNDA Filed With FDA for Darolutamide Plus ADT in mHSPC

• A supplemental new drug application (sNDA) seeking expanded indication for darolutamide (Nubeqa) given with androgen deprivation therapy (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC) has been submitted to the FDA.
• Data from the phase 3 ARANOTE trial (NCT04736199) support this submission.
• Currently, darolutamide is approved by the FDA for use in combination with docetaxel for the treatment of patients with mHSPC and as a monotherapy for patients with nometastatic castration-resistant prostate cancer.

The FDA has received an sNDA seeking expanded indication for the combination of darolutamide and ADT for the treatment of patients with mHSPC.¹

Findings from the phase 3 ARANOTE trial (NCT04736199) support the sNDA. In the study, experts evaluated the combination of darolutamide, an oral androgen receptor inhibitor, with ADT vs placebo plus ADT in patients with mHSPC.²

Results presented at the 2024 ESMO Congress showed that at a data cutoff of June 7, 2024, there was a 46% reduced risk of radiographic progression or death with the darolutamide combination 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. The findings were simultaneously published in The Journal of Clinical Oncology.

“Simply put, our ambition is to help more patients with prostate cancer,” said Christine Roth, executive vice president of Global Product Strategy and Commercialization and member of the Pharmaceuticals Leadership Team at Bayer, in a press release.¹ “We are proud of the role [darolutamide] currently plays in the treatment of mHSPC and with this FDA submission, hope to expand the use of [darolutamide] to more patients with the disease, regardless of chemotherapy use.”

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

Prostate cancer, bladder cancer, men's health care: © Tom - stock.adobe.com

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.

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. Bayer submits supplemental new drug application to U.S. FDA seeking expanded indication for NUBEQA® (darolutamide) in metastatic hormone-sensitive prostate cancer. News Release. Bayer. September 26, 2024. Accessed September 26, 2024. https://tinyurl.com/y6tdjnu4

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