Darolutamide Review is Fast Tracked by FDA

The new prostate cancer drug darolutamide has been fast tracked by the Food and Drug Administration (FDA), just two months after Bayer and Orion reported positive data from a Phase III trial. Darolutamide is a nonsteroidal androgen receptor inhibitor for men with late-stage prostate cancer that has not spread but continues to grow even though testosterone levels are low. This form of cancer is known as hormone-resistant or castration-resistant.

Androgen receptor inhibitors are drugs that slow down or halt the growth of cancer cells. They work by inhibiting the activity of androgen hormones; that is, testosterone.

If darolutamide is approved by the FDA, it will join two other drugs already on the market designed for the same population of prostate cancer patients. Those two drugs are Pfizer’s Xtandi and Johnson & Johnson’s Erleada. Let’s look at darolutamide first.

Darolutamide vs placebo phase III study

The multicenter, placebo-controlled, randomized phase III study that prompted Bayer and Orion to push for fast tracking was ARAMIS, which involved 1,509 men who were already being treated with androgen deprivation therapy (ADT) and also at high risk of having their cancer spread. The men were randomized 2:1 to receive darolutamide at 600 mg two times a day plus ADT or placebo plus ADT.

Overall, the results of the study showed that the drug:

  • Reduced the risk of metastasis or death by 59 percent when compared with placebo
  • Achieved a median metastasis-free survival of 40.4 months compared with 18.4 months for placebo
  • Three-year rates of overall survival were 83 percent for men who took darolutamide versus 73 percent in the placebo group, for a 29 percent reduction in the risk of dying
  • Median time to progression of pain was 40.3 months for darolutamide versus 25.4 months for placebo, translating into a 35 percent reduced risk
  • Median progression-free survival was 36.8 months for men who took darolutamide versus 14.8 months for those who received placebo, which was a 62 percent reduced risk
  • Adverse events were similar between the darolutamide and placebo groups when it came to fatigue, incidence of fractures and falls, and hypertension. The most common side effects that have surfaced in clinical trials for darolutamide include anemia, diarrhea, fatigue, weakness, hot flashes, and decreased appetite.

Darolutamide vs Erleada and Xtandi

Let’s look at two other androgen receptor inhibitors and how they compare with darolutamide: Erleada (apalutamide) and Xtandi (enzalutamide).

Erleada was approved on February 14, 2018, by the FDA for treatment of men with nonmetastatic hormone-resistant prostate cancer. It was the first FDA-approved drug for this group of men with prostate cancer. The phase III clinical trial that helped launch the drug was the SPARTAN study.

The SPARTAN study involved 1,207 men with nonmetastatic hormone-resistant prostate cancer who no longer responded to hormone therapy and were at high risk of metastasis. The participants were randomized in a 2:1 ratio to receive apalutamide or placebo while still taking their androgen-deprivation therapy.

Use of apalutamide reduced the risk of metastasis and death by 72 percent when compared with the placebo group. Median metastasis-free survival was extended by 2 years (40.5 months in the apalutamide group vs 16.2 months in placebo). Apalatamide was also associated with a 55 percent risk reduction in the time to symptomatic disease progression.

Side effects associated with apalutamide include fatigue, hypertension, rash, diarrhea, nausea, weight loss, joint pain, and fractures.

Xtandi was approved on August 31, 2012, for men with advanced prostate cancer that has spread (metastasized) or recurred despite treatment with hormone therapy and docetaxel (chemotherapy). Then in July 2018, it was approved for nonmetastatic, hormone-resistant prostate cancer, based on the findings of the multicenter PROSPER clinical trial.

In the PROSPER trial, 1,401 men were randomly assigned on a 2:1 basis to either enzalutamide (160 mg once daily) or placebo. Median metastasis-free survival was 36.6 months for men who took enzalutamide and 14.7 months for those taking placebo. The most common adverse reactions that occurred more often than in the placebo group were fatigue, hot flushes, hypertension, dizziness, nausea, and falls.

According to Bayer, darolutamide has “inherently different pharmacokinetics” than their competitors, resulting in lower risk for drug-drug interactions and less central nervous system toxicity.

The bottom line

Based on study results, the median metastasis-free survival for Xtandi, Erleada, and darolutamide are 36.6 months, 40.5 months, and 40.4 months, respectively. Men with nonmetastatic, hormone-resistant prostate cancer who are at risk of metastasis should discuss their treatment options with their management team to determine whether any of these drugs suit their lifestyle, preferences, and needs.

Read more in our Prostate Cancer Health Center.


American Association for Cancer Research. Darolutamide slows metastasis in prostate cancer. Cancer Discovery 2019 Apr; 9(4)

The ASCO Post. FDA approved enzalutamide for castration-resistant prostate cancer. 2018 Jul 25

Bayer. US FDA accepts new drug application and grants priority review for darolutamide. 2019 Apr 29

Columbus G. Darolutamide granted priority review by FDA for treatment of nonmetastatic CRPC. Targeted Oncology 2019 Apr 29

Goodman A. Apalutamide, enzalutamide improve metastasis-free survival in nonmetastatic castrate-resistant prostate cancer. The ASCO Post 2018 Mar 10

Prostate Cancer News Today. ODM-201 (darolutamide)

Tong A. FDA tags Bayer’s prostate cancer drug for priority review as drugmaker gears up against rivals. Endpoints News 2019 Apr 29

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