Enzalutamide Set to Gain New Indication in China Following Apalutamide's Approval

Text | Dopine

Recently, the second marketing application for Astellas’ prostate cancer drug enzalutamide soft capsules in China (with the relevant acceptance number JXHS1900163) has had its status updated to "Under Review" by the NMPA. This indicates that the new indication is expected to be approved soon. Based on the rationale for including this marketing application in the priority review process, the upcoming approved indication is non-metastatic castration-resistant prostate cancer (nmCRPC).

Enzalutamide (Xtandi) is an androgen receptor signaling inhibitor that directly targets the androgen receptor (AR) and acts at three steps in the AR signaling pathway: (1) inhibition of androgen binding—binding induces conformational changes that trigger receptor activation; (2) prevention of nuclear translocation—the translocation of AR to the nucleus is an essential step in AR-mediated gene regulation; and (3) impairment of DNA binding—the binding of AR to DNA is critical for regulating gene expression. The drug was initially co-developed by Medivation and Astellas; however, in August 2016, Pfizer acquired the product through its $14 billion acquisition of Medivation.

Xtandi was first approved by the FDA in August 2012 for the treatment of metastatic castration-resistant prostate cancer (mCRPC) in patients who had previously received docetaxel or paclitaxel therapy. In 2014, it was further approved for the treatment of mCRPC in patients who had not previously undergone chemotherapy. In July 2018, the FDA approved the drug for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC), and subsequently, in December 2019, it was approved for the treatment of metastatic hormone-sensitive prostate cancer (mHSPC).

In countries where it is marketed, enzalutamide is the standard of care for men with metastatic castration-resistant prostate cancer. Since 2012, more than 420,000 patients worldwide have received this medication. Moreover, as its approved indications and scope have expanded, global sales of Xtandi have risen year by year; reportedly, its global sales reached USD 3.624 billion in 2018 and surged to USD 4.3 billion in 2019.

However, the drug was approved relatively late in China. It was not until November 2019 that the NMPA approved it for adult patients with metastatic castration-resistant prostate cancer (mCRPC) who are asymptomatic or mildly symptomatic and have not received chemotherapy after failure of androgen deprivation therapy (ADT). Its brand name is Xtandi. With the future approval of this new indication, enzalutamide will become the first oral medication approved in China for the treatment of both metastatic and non-metastatic castration-resistant prostate cancer.

Furthermore, according to the Insight database, Astellas has registered four clinical trials for enzalutamide in China, with indications including mCRPC, nmCRPC, and mHSPC. It is expected that the company will also submit a marketing application for the new indication of mHSPC in China in the future.

According to the Insight database, the compound patent for enzalutamide in China will expire in 2026. However, Hansoh Pharmaceutical has already submitted a marketing application for enzalutamide soft capsules as a Class 4 generic drug. In addition, Sichuan Kelun, Qilu Pharmaceutical, and Shenyang Hongqi Pharmaceutical are also conducting bioequivalence (BE) trials.

Moreover, when discussing enzalutamide, it is imperative to mention another second-generation androgen receptor (AR) inhibitor—apalutamide. This drug is also a blockbuster in the field of prostate cancer. The renowned pharmaceutical market research firm EvaluatePharma previously published a forecast predicting that its global sales would reach $2.115 billion in 2024. Apalutamide was approved in China earlier than enzalutamide; it was approved by the National Medical Products Administration (NMPA) in September 2019 for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC) with a high risk of metastasis, under the brand name Erleada. Furthermore, this August, the drug received additional approval for the treatment of metastatic castration-sensitive prostate cancer (mCSPC). Given the overlap in indicated patient populations, it is anticipated that these two drugs will engage in intense competition within the domestic prostate cancer treatment landscape in the future.