Bayer's Darolutamide Approved in China for Non-Metastatic Castration-Resistant Prostate Cancer

Recently, according to the NMPA website, the approval document for Bayer's androgen receptor inhibitor "ODM-201 300mg film-coated tablets" is pending collection, which means that the drug has been officially approved in China. The indication is: non-metastatic castration-resistant prostate cancer (nmCRPC).

Prostate cancer is the second most common malignant tumor in men worldwide, with approximately 1.41 million new cases diagnosed and about 380,000 deaths globally in 2020. Non-metastatic castration-resistant prostate cancer (nmCRPC) is an advanced form of prostate cancer in which the disease continues to progress despite testosterone levels being reduced to very low levels.

ODM-201 (darolutamide) is a highly active androgen receptor inhibitor (ARI) jointly developed by Bayer and Orion Corporation. With its unique chemical structure, it inhibits the growth of prostate cancer cells while limiting the burden of side effects on patients’ daily lives. Bayer leads the global commercialization of this drug; in certain European markets, including France, Germany, Italy, Spain, the United Kingdom, Scandinavia, and Finland, it is co-promoted by Bayer and Orion Corporation. The drug was approved in the United States in July 2019 and in the European Union in March 2020 for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC), under the brand name Nubeqa.

The approval of this drug was based on the results of the pivotal Phase III ARAMIS study. This study was a randomized, double-blind, placebo-controlled, multicenter Phase III trial designed to evaluate the safety and efficacy of darolutamide in patients with non-metastatic castration-resistant prostate cancer (nmCRPC) who were receiving androgen deprivation therapy (ADT) and had a high risk of disease metastasis. In the study, 1,509 patients were randomly assigned in a 2:1 ratio to two groups: one group received oral darolutamide 600 mg twice daily in combination with ADT, while the other group received oral placebo in combination with ADT.

The results showed that, compared with placebo plus ADT, the darolutamide treatment group demonstrated a significant improvement in median metastasis-free survival (MFS) (40.4 months vs. 18.4 months) and reduced the risk of metastasis or death by 59%. Regarding safety, the most common adverse reactions in the study (occurring at a rate ≥2% higher than in the placebo plus ADT group) were fatigue/asthenia (16% vs. 11%), pain in extremities (6% vs. 3%), and rash (3% vs. 1%).

In China, darolutamide was submitted for marketing approval in February 2020 and subsequently included in the priority review program. With the reform of China’s drug approval system, the drug was officially approved in the country within less than a year.

Regarding androgen receptor inhibitors (ARIs), multiple products have previously been approved in China for the treatment of prostate cancer, such as bicalutamide, enzalutamide, apalutamide, flutamide, and nilutamide, among which enzalutamide and apalutamide belong to the second-generation ARIs. As the first globally approved second-generation AR inhibitor, enzalutamide achieved the highest sales, reaching $3.624 billion in 2018, with indications approved in China including mCRPC and nmCRPC. Apalutamide has been approved in China for the treatment of nmCRPC and mCSPC, and industry forecasts predict its global sales could reach $2.115 billion by 2024.

In addition, several investigational androgen receptor inhibitors are under development, including SHR3680 from Hengrui Medicine, proxalutamide from Kintor Pharmaceutical, and HC-1119 (darolutamide) from Haisco/Huichuang. Currently, the clinical trials of these three drugs for prostate cancer are in Phase III. Besides treating prostate cancer, Kintor Pharmaceutical’s proxalutamide is also being developed for the treatment of novel coronavirus. Recent research results indicate that this drug is effective in both men and women, significantly reducing the progression of COVID-19 patients from mild to severe cases.