Janssen's Apalutamide Approved in China, Intensifying Competition in Prostate Cancer Market

Author: Holly

On September 6, 2019, the National Medical Products Administration updated the application status of apalutamide (Erleada®), a targeted therapy for prostate cancer developed by Xian Janssen, to “Approval Completed – Pending Certificate Issuance.”

Apalutamide is a second-generation non-steroidal androgen receptor (AR) inhibitor, initially developed by the University of California in the United States. In 2009, it was exclusively licensed to Aragon Pharmaceuticals for development. In August 2013, Johnson & Johnson acquired Aragon, and its subsidiary, Janssen Pharmaceuticals, took responsibility for further development, regulatory approval for market launch, manufacturing, and sales.

Seizing the First-Mover Advantage in the Non-Metastatic CRPC Market

Globally, prostate cancer is the second leading cause of cancer-related death in men, surpassed only by lung cancer. Prostate cancer is often driven by excessive levels of male hormones, including testosterone (an androgen). Therefore, standard treatment aims to reduce androgen levels in patients, which can be achieved clinically through surgical castration and/or androgen deprivation therapy (ADT).

Currently, the castration-resistant prostate cancer (CRPC) market is dominated by Johnson & Johnson’s next-generation oral anti-androgen drug Zytiga (abiraterone) and Astellas/Pfizer’s Xtandi (enzalutamide); however, both products were initially approved for the treatment of metastatic CRPC. Prior to February 2018, the U.S. FDA had not approved any drug for the treatment of non-metastatic CRPC.

Molecular Structural Formula of Apalutamide

Although Zytiga and Xtandi are both actively expanding their market share and attempting to capture the non-metastatic castration-resistant prostate cancer (nmCRPC) market, Apalutamide gained the first-mover advantage. On February 14, 2018, Apalutamide received approval from the U.S. Food and Drug Administration (FDA) for the treatment of nmCRPC, becoming the first drug globally approved for this indication and the first novel anticancer agent to be approved based on metastasis-free survival (MFS) as a clinical endpoint. It is marketed under the brand name Erleada®. Notably, this approval came two months ahead of the Prescription Drug User Fee Act (PDUFA) deadline, with only four months elapsing between the acceptance of the New Drug Application (NDA) and final approval.

The data supporting the approval of Erleada came from a pivotal Phase III clinical trial named SPARTAN. The trial results showed that Erleada significantly extended metastasis-free survival by 24.3 months compared to placebo, with a 72% reduction in the risk of distant metastasis and death.

Clinical Urgent Need + Priority Review: Rapid Approval in China

Xian Janssen submitted the marketing application for apalutamide in China in March 2019, and it was accepted by the Center for Drug Evaluation (CDE) on March 15, 2019, with the acceptance number JXHS1900036. On April 29, the marketing application for apalutamide tablets was proposed to be included in the list of priority reviews. Due to its significant clinical advantages, apalutamide was also included in the second batch of urgently needed overseas new drugs. From the acceptance of the marketing application to official approval, apalutamide took less than six months.

As early as 2014, Aragon Pharmaceuticals submitted an application for import clinical trials of the drug to China’s regulatory authorities, but the final review conclusion was “not approved.” One year later, Aragon reapplied, and the final review conclusion was “approved for clinical trials.” Between 2016 and 2018, Aragon submitted multiple supplemental applications. The most recent registration information pertains to a supplemental application filed on June 6, 2019.

Table 1 Registration Information for Apalutamide Submitted in China

Source: CDE Official Website

According to the China Drug Clinical Trial Registration and Information Publicity Platform, apalutamide is currently undergoing three clinical trials in China, namely:

Clinical Study of Apalutamide Combined with Androgen Deprivation Therapy for Prostate Cancer;

A Phase I Study of Monotherapy in Subjects with Metastatic Castration-Resistant Prostate Cancer;

Clinical Study of JNJ-56021927 Combined with Radiotherapy in the Treatment of Prostate Cancer.

Table 2. Clinical Trials of Apalutamide Currently Underway in China

Source: China Drug Clinical Trial Registration and Information Publicity Platform

“Clash of the Titans” Unfolds in the Prostate Cancer Field

Currently, in the field of prostate cancer treatment, Astellas/Pfizer’s Xtandi and Johnson & Johnson’s Zytiga are the two best-selling products. However, this landscape is gradually changing with the launch of more blockbuster new drugs and the expiration of patents for certain medications. In July 2018, EvaluatePharma predicted the following list of the “Top-Selling Drugs in the Global Prostate Cancer Market in 2024”:

Since its launch in 2011, Zytiga has dominated the market. However, its U.S. patent expired in October 2018. As more than half of the drug’s sales came from markets outside the United States, global sales of Zytiga continued to rise in 2018, reaching $3.498 billion according to the company’s financial report. Nevertheless, EvaluatePharma predicts that due to competition from generic drugs in the U.S. market, Zytiga’s sales will plummet after 2018, with global sales dropping to just $382 million by 2024.

Although Xtandi was launched one year later than Zytiga, its sales grew rapidly, surpassing Zytiga for the first time in global sales in 2017, reaching $2.654 billion. Meanwhile, Xtandi demonstrated positive results in the PROSPER clinical trial for non-metastatic castration-resistant prostate cancer (nmCRPC), extending metastasis-free survival by 21.9 months and reducing the risk of metastatic progression or death by 71%. In January 2018, Xtandi’s marketing application for this indication was submitted to the U.S. Food and Drug Administration (FDA). In July and November 2018, Xtandi received approval from the U.S. FDA and the European Union, respectively, for adult patients with nmCRPC at high risk of metastasis. This approval made Xtandi the first oral medication indicated for both metastatic and non-metastatic CRPC. The expansion of indications will serve as a key catalyst for Xtandi’s next leap in growth. According to EvaluatePharma forecasts, Xtandi’s global sales are projected to reach $4.467 billion in 2024, establishing it as a “blockbuster” in the field of prostate cancer.

Leveraging its first-mover advantage in non-metastatic castration-resistant prostate cancer (nmCRPC), along with potential indications including metastatic hormone-sensitive prostate cancer (mHSPC; TITAN trial), locally advanced/high-risk localized prostate cancer (ATLAS trial), and combination therapy with abiraterone for chemotherapy-naïve metastatic CRPC, the industry holds a highly favorable outlook on the commercial prospects of Erleada. EvaluatePharma predicts that the drug will be rapidly adopted by the market following its launch, with global sales expected to reach $2.115 billion in 2024, second only to Xtandi.

In addition to the three aforementioned drugs, Bayer’s darolutamide (approved by the FDA on July 31, 2019, for the treatment of patients with non-metastatic castration-resistant prostate cancer [nmCRPC]) and Endocyte’s (acquired by Novartis in 2018) 177Lu-PSMA-617 will inject new vitality into the prostate cancer drug market. EvaluatePharma predicts that the 2024 sales of these two drugs will reach $757 million and $521 million, respectively.

Bayer’s other product, Xofigo (rejected for approval by the NMPA in May 2019), is expected to experience slow growth over the next six years. The company’s financial report shows that the drug’s sales in 2018 amounted to USD 387 million. AstraZeneca’s Zoladex is projected to see a gradual decline in sales over the next six years, with estimated sales reaching USD 405 million in 2024.

References:

1. NMPA Official Website, CDE Official Website, Company Financial Reports, etc.

2. Clarivate: “Most Promising Drug Predictions” 2018 Annual Report

3、 The prostate cancer outlook