FDA Approves Darolutamide for Non-metastatic Castration-resistant Prostate Cancer

Approval is based on evidence from the ARAMIS study

On 30 July 2019, the US Food and Drug Administration (FDA) approved darolutamide (NUBEQA, Bayer HealthCare Pharmaceuticals Inc.) for non-metastatic castration-resistant prostate cancer.

Approval was based on evidence from the ARAMIS (NCT02200614), a multicentre, double-blind, placebo-controlled clinical trial in 1,509 patients with non-metastatic castration-resistant prostate cancer. Patients were randomised (2:1) to receive either 600 mg darolutamide orally twice daily (n=955) or matching placebo (n=554). All patients received a gonadotropin-releasing hormone (GnRH) analogue concurrently or had a previous bilateral orchiectomy. Twelve patients with previous seizure histories were treated on the darolutamide arm.

The primary endpoint was metastasis free survival (MFS), defined as the time from randomisation to first evidence of distant metastasis or death from any cause within 33 weeks after the last evaluable scan, whichever occurred first. The median MFS was 40.4 months (95% CI: 34.3, not reached) for patients treated with darolutamide compared with 18.4 months (95% CI: 15.5, 22.3) for those receiving placebo (hazard ratio 0.41; 95% CI: 0.34, 0.50; p < 0.0001). Overall survival data were not mature.

The most common adverse reactions (≥2%) in patients who received darolutamide were fatigue, pain in extremity, and rash. Ischemic heart disease (4.3%) and heart failure (2.1%) were more common on the darolutamide arm. The seizure incidence was similar on the two arms (0.2%).

The recommended darolutamide dose is 600 mg (two 300 mg tablets) administered orally twice daily with food. Patients should also receive a GnRH analogue concurrently or should have had bilateral orchiectomy.

Full prescribing information for NUBEQA is available here.

FDA granted darolutamide fast track designation. FDA granted this application priority review.

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.