FDA Accepts sNDA for Darolutamide/ADT in Hormone-Sensitive Prostate Cancer

Darolutamide with androgen deprivation therapy has shown promising efficacy and safety results for patients with hormone-sensitive prostate cancer.

For patients with metastatic hormone-sensitive prostate cancer (HSPC), a supplemental new drug application (sNDA) for the oral androgen receptor (AR) inhibitor darolutamide (Nubeqa) in combination with androgen deprivation therapy (ADT) has been accepted by the FDA, according to a press release from the developer, Bayer.¹

Results from the randomized, double-blind, placebo-controlled phase 3 ARANOTE trial (NCT04736199) found that darolutamide plus ADT, when compared with placebo plus ADT, reduced the risk of disease progression or death in patients with metastatic HSPC significantly. These findings support the sNDA for darolutamide/ADT in this population.

At the primary data cutoff date, darolutamide plus ADT reduced the risk of radiological progression by 46% (HR, 0.54; 95% CI, 0.41-0.71; P <.0001).² Overall survival (OS) results also indicated a benefit with darolutamide vs placebo, as 23.1% of patients died vs 26.9% in each arm, respectively (HR, 0.81; 95% CI, 0.59-1.12).

Regarding safety, grade 3 or 4 adverse events (AEs) occurred in 30.8% of patients receiving darolutamide and 30.3% of patients receiving placebo. Deaths due to AEs occurred in 4.7% of the darolutamide group and 5.4% of the placebo group.

Anemia, arthralgia, and urinary tract infection were the only AEs to exceed 10% incidence in the darolutamide group.

Christine Roth, executive vice president of Global Product Strategy and Commercialization and Member of the Pharmaceuticals Leadership team at Bayer said in a press release, “…Today’s acceptance of our sNDA application for [darolutamide] plus ADT for the treatment of patients with [metastatic] HSPC brings us closer to adding an additional treatment option for [darolutamide] to benefit those living with [metastatic] HSPC. If approved, this would expand the indication for [darolutamide] in patients with [metastatic] HSPC to include [darolutamide] both with and without chemotherapy, providing physicians and their patients with an additional [darolutamide] treatment option in this setting.”¹

Radiological progression-free survival (PFS), measured as time from the date of randomization to the time of the first documentation of radiological disease progress or death, was the primary end point. Secondary end points were OS, time from randomization to the date of the first castration-resistant event, and time to initiation of subsequent anti-cancer therapy, among others.

The current indication for darolutamide is in the treatment of adult patients with metastatic HSPC in combination with docetaxel (Docefrez) and in the treatment of adult patients with non-metastatic castration-resistant prostate cancer.

Patients were randomly assigned to be in 1 of 2 trial arms. Those in the experimental arm were administered 600 mg of darolutamide, in the form of two 300 mg tablets, to be taken twice daily with food and investigator’s choice of ADT as a standard therapy. Patients in the placebo arm of the study were administered a placebo twice daily with food and investigator’s choice of ADT as a standard therapy.

A total of 669 patients who are male and aged 18 or older were enrolled in the trial. Inclusion criteria were histologically or cytologically confirmed adenocarcinoma of prostate; metastatic disease; an ECOG score from 0 to 2; adequate bone marrow, liver, and renal function; and having started ADT with or without first generation anti-androgen agents no earlier than 12 weeks before randomization.³

Patients were excluded if they had radiotherapy within 2 weeks before randomization, uncontrollable hypertension, any prior malignancy within 5 years of randomization, and an inability to swallow oral medications, among others.

The trial was held in 15 countries: Australia, Brazil, Canada, Chile, China, India, Latvia, Lithuania, New Zealand, Peru, Russian Federation, South Africa, Spain, Taiwan, and Ukraine.

Beyond the ARANOTE trial, darolutamide is currently undergoing a clinical development program that includes the phase 3 ARASTEP trial (NCT05794906) investigating the agent with ADT compared with ADT alone in patients with HSPC with high-risk biochemical recurrence, and the phase 3 DASL-HiCAP trial (NCT04136353) investigating darolutamide as an adjuvant treatment for localized prostate cancer with high risk of recurrence.

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. November 21, 2024. Accessed on November 21, 2024. https://tinyurl.com/36p5u9pb
2. 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. Published online September 16, 2024. doi:10.1200/JCO-24-01798
3. Darolutamide in addition to ADT versus ADT in metastatic hormone-sensitive prostate cancer (ARANOTE). ClinicalTrials.gov. Last updated November 21, 2024. Accessed on November 21, 2024. https://tinyurl.com/zkj5ua8p