FDA Approves Darolutamide Tablets for Metastatic Hormone-Sensitive Prostate Cancer

Efficacy was based on ARASENS (NCT02799602), a randomized, multicenter, double-blind, placebo-controlled clinical trial of 1,306 patients with mHSPC. Patients were randomized to receive either darolutamide 600 mg orally twice daily plus docetaxel 75 mg/m² intravenously administered every three weeks for up to six cycles or docetaxel plus placebo. All patients received a gonadotropin-releasing hormone analog concurrently or had a bilateral orchiectomy.

The primary efficacy measure was overall survival (OS). Time-to-pain progression was an additional efficacy measure. Median OS was not reached (NR) (95% CI = NR, NR) in the darolutamide plus docetaxel arm and 48.9 months (95% CI = 44.4, NR) in docetaxel plus placebo arm (HR = 0.68; 95% CI = 0.57, 0.80; p < 0.0001). Treatment with darolutamide and docetaxel resulted in a statistically significant delay in time-to-pain progression (HR = 0.79; 95% CI = 0.66, 0.95; 1-sided p = 0.006).

Patients’ median age was 67 years (range = 41–89), and 17% were aged 75 or older. Among study participants, 52% were White, 36% Asian, 7% Hispanic/Latino, and 4% Black or African American. Three percent of patients had M1a disease (spread to distant lymph nodes), 83% had M1b (spread to bones), and 14% had M1c (spread to organs).

The most commonly reported adverse reactions (≥ 10% with a ≥ 2% increase over placebo with docetaxel) were constipation, decreased appetite, rash, hemorrhage, increased weight, and hypertension. The most commonly reported laboratory test abnormalities (≥ 30%) were anemia, hyperglycemia, decreased lymphocyte count, decreased neutrophil count, increased AST, increased ALT, and hypocalcemia.

The recommended darolutamide dose for mHSPC is 600 mg (two 300 mg tablets) taken orally, twice daily, with food, until a patient experiences unacceptable toxicity or disease progression. Docetaxel, 75 mg/m² intravenously, is administered every three weeks for up to six cycles. The first dose of docetaxel should be administered within six weeks after the start of darolutamide treatment.

View full prescribing information for darolutamide (https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/212099s002lbl.pdf).

The review was conducted under Project Orbis (https://www.fda.gov/about-fda/oncology-center-excellence/project-orbis), an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For this review, FDA collaborated with Health Canada, the Singapore Health Sciences Authority, Switzerland’s Swissmedic, the United Kingdom’s Medicines and Healthcare products Regulatory Authority, and Australia’s Therapeutic Goods Administration. The application reviews may be ongoing at the other regulatory agencies.

The review used the Real-Time Oncology Review (https://www.fda.gov/about-fda/oncology-center-excellence/real-time-oncology-review-pilot-program) pilot program, which streamlined data submission prior to the filing of the entire clinical application, and  Assessment Aid (https://www.fda.gov/about-fda/oncology-center-excellence/assessment-aid), a voluntary submission from the applicant to facilitate FDA’s assessment. FDA approved the application approximately one month ahead of the goal date.

The application was granted priority review. A description of FDA expedited programs can be found in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics (https://www.fda.gov/regulatory-information/search-fda-guidance-documents/expedited-programs-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 (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.

For assistance with single-patient investigational new drug applications, contact OCE’s Project Facilitate (https://www.fda.gov/about-fda/oncology-center-excellence/project-facilitate) at 240-402-0004 or email OncProjectFacilitate@fda.hhs.gov (mailto:OncProjectFacilitate@fda.hhs.gov).