FDA Approves Darolutamide for Non-Metastatic Castration-Resistant Prostate Cancer

July 31, 2019

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

Approval was based on ARAMIS (NCT02200614), a multicenter, double-blind, placebo-controlled clinical trial in 1,509 patients with non-metastatic castration resistant prostate cancer. Patients were randomized (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) analog 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 randomization 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). OS 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 gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy.

View full prescribing information for NUBEQA.

FDA granted darolutamide fast track designation. FDA granted this application priority review. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

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 or by calling 1-800-FDA-1088.

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