Janssen-Cilag Announces NMPA Approval of Erleada® (Apalutamide) for High-Risk Non-Metastatic Castration-Resistant Prostate Cancer in China

Beijing, September 10, 2019 /PRNewswire/ -- Johnson & Johnson's pharmaceutical subsidiary in China, Xian Janssen Pharmaceutical Ltd., announced today that its product Erleada^®(Apalutamide Tablets) received accelerated approval from the National Medical Products Administration for the treatment of adult patients with non-metastatic castration-resistant prostate cancer (NM-CRPC) at high risk of metastasis.^[1]. In May this year, the Center for Drug Evaluation (CDE) of the National Medical Products Administration due to Ansenke^®Significant clinical advantage grants it "Priority Review" status, and Nubeqa^®Included in the second batch of the List of Overseas New Drugs Urgently Needed for Clinical Use. Non-metastatic castration-resistant prostate cancer (nmCRPC) is defined as prostate cancer characterized by prostate-specific antigen (PSA) progression following medical or surgical castration, with no evidence of distant metastasis detected by conventional imaging. Clinical studies have demonstrated that the use of Erleada^®Treatment reduced the risk of distant metastasis or death by 72%, and median metastasis-free survival (MFS) was extended by more than two years (24.31 months).

Erleada^®It is the first next-generation androgen receptor inhibitor approved in China for patients with non-metastatic castration-resistant prostate cancer. It blocks the androgen signaling pathway in prostate cancer cells, inhibiting cancer cell growth through three mechanisms: inhibiting the binding of androgens to the androgen receptor (AR), inhibiting the nuclear translocation of activated AR, and inhibiting the binding of AR to deoxyribonucleic acid (DNA) in cancer cells, thereby blocking AR-mediated transcription.

Over the past decade, the incidence of prostate cancer in China has been on the rise, and it has now become the fifth most common cancer among Chinese men.^[2]. If the PSA level rises in prostate cancer patients after receiving androgen deprivation therapy (ADT), it may indicate a decline or failure in treatment efficacy, suggesting that the patient may have entered the castration-resistant stage. Without timely intervention, cancer cells may metastasize distantly to other organs and sites outside the prostate, such as the bones, liver, and lungs, posing a serious threat to the patient's life. Although there has been some progress in the treatment of prostate cancer in recent years, metastatic castration-resistant prostate cancer remains a fatal disease.

Professor Sun Yinghao, an academician of the Chinese Academy of Engineering and Chairman of the Urology Branch of the Chinese Medical Association, pointed out, “Delaying metastasis is crucial for the treatment of prostate cancer. Data show that nearly 90% of patients with castration-resistant prostate cancer will eventually develop bone metastases.”^[3], symptoms such as pain, fractures, and spinal cord compression may occur. Once cancer cells metastasize, the patient’s overall health status and prognosis will deteriorate. We fully understand the feelings of patients or their families upon hearing the news of “cancer metastasis.” Erleada^®Its approval enables physicians to help patients with non-metastatic castration-resistant prostate cancer delay the onset of metastasis.”

Erleada^®The approval was based on Phase III data from the global, multicenter, double-blind, randomized, placebo-controlled SPARTAN clinical trial.^[1], this study evaluated 1,207 patients with non-metastatic castration-resistant prostate cancer who were randomly assigned (2:1) to receive once-daily oral apalutamide^®(240 mg) treatment (N=806) or once-daily placebo treatment (N=401). These patients had previously experienced a rapid rise in PSA while on androgen deprivation therapy. All patients in the SPARTAN study received concurrent GnRHa therapy or had undergone bilateral orchiectomy, and these patients were required to maintain ADT.

Among the primary endpoints of the trial, Erleada^®Median Metastasis-Free Survival in Treated Patients^[4](MFS) showed a statistically significant improvement, reaching 40.51 months, which is more than two years longer (24.31 months) than the 16.20 months observed in patients receiving placebo treatment, with a 72% reduction in the risk of distant metastasis or death (HR = 0.28; 95% CI, 0.23-0.35; P<0.0001). Other efficacy endpoints, including time to metastasis (TTM), progression-free survival (PFS), and time to symptom progression, all demonstrated statistically significant improvements. Among these, Erleada^®The median progression-free survival in the study group was 40.51 months, compared to 14.72 months in the placebo group (HR=0.29; 95% CI, 0.24-0.36; P<0.0001).^[1]

Among the exploratory endpoints, Erleada^®Compared with the placebo group, the treatment group reduced the risk of PSA progression by 94% (HR = 0.06; 95% CI, 0.05–0.08; P < 0.0001); 93% of patients achieved a ≥50% reduction in PSA from baseline, with a median time to 50% PSA reduction of 0.95 months.^[5],[6]

Additionally, Erleada^®The most common adverse reactions (≥20%) in the treatment group were fatigue, hypertension, rash, and diarrhea.^[1]

Professor Sun Yinghao stated, “The SPARTAN study has fully confirmed that Erleada^®The clinical benefits brought to patients with non-metastatic castration-resistant prostate cancer also highlight the value of Erleada for these patients.^®The Importance of Treatment. Currently, Erleada^®Included in multiple international guidelines for the treatment of prostate cancer^[7],[8]"Recommended as a Class I or Grade A treatment for patients with non-metastatic castration-resistant prostate cancer."

Asgar Rangoonwala, President of Xian Janssen Pharmaceutical Ltd., stated: “We are pleased that Erleada^®It has become the first approved treatment regimen for non-metastatic castration-resistant prostate cancer in China. We will work closely with the government and relevant authorities to introduce this important, innovative treatment regimen as soon as possible, thereby serving Chinese patients more rapidly and extensively. Given that “not all prostate cancers are the same,” we will continue to explore and develop the therapeutic potential of ERLEADA® across different stages of prostate cancer through additional clinical programs, to further meet the diverse treatment needs of patients.

Erleada^®is Xian Janssen's follow-up to Zytiga^®(Abitaterone Acetate Tablets) represents another innovative solution brought to the domestic prostate cancer field. Previously, Zytiga^®Approved in 2015 and 2018, respectively, for use in combination with prednisone or prednisolone to treat patients with metastatic castration-resistant prostate cancer (mCRPC) and patients with newly diagnosed high-risk metastatic hormone-sensitive prostate cancer (mHSPC).

Erleada^®Approved by the U.S. Food and Drug Administration (FDA) on February 14, 2018, for the treatment of patients with non-metastatic castration-resistant prostate cancer (NM-CRPC), and subsequently approved in Canada, Australia, Argentina, Brazil, Europe, and Japan.^{[9],[10],[11],[12],[13]}。

^[1]Apalutamide Tablets Package Insert (2019)
^[2] CA Cancer J Clin. 2016 Mar-Apr;66(2):115-32. doi: 10.3322/caac.21338. Epub 2016 Jan 25.
^[3] Sade, J.P., Báez, C.A.V., Greco, M. et al. Med Oncol (2018) 35: 56. https://doi.org/10.1007/s12032-018-1105-8
^[4]Metastasis-Free Survival (MFS) is defined as the time from randomization to the first occurrence of either distant metastasis confirmed by Blinded Independent Central Review (BICR)—defined as new lesions in bone or soft tissue, or lymph node enlargement above the bifurcation of the common iliac arteries—or death from any cause, whichever occurs first.
^[5] Smith MR, et al. N Engl J Med. 2018 Apr 12; 378(15): 1408-1418.
^[6] Small EJ, et al. Oral presentation at AUA 2018; abstract PD10-11.
^[7] https://doi.org/10.1016/j.juro.2018.02.621
^[8] NCCN Guideline. Prostate Cancer. Version 3 2019.
^[9] FDA. FDA approves new treatment for a certain type of prostate cancer using novel clinical trial endpoint. Available at https://www.fda.gov/newsevents/newsroom/pressannouncements/ucm596768.htm. Last accessed October 2018.  
^[10] Pan-Canadian Oncology Drug Review. Available at: https://cadth.ca/sites/default/files/pcodr/pcodr_apalutamide_erleada_crpc_in_cgr%20.pdf. Last accessed October 2018.
^[11] ERLYAND^®. Australian Product Information. Available at: https://www.janssen.com/australia/sites/www_janssen_com_australia/files/prod_files/live/erlyand_pi.pdf Last accessed October 2018.

^[12] ERLEADA^® Identificação Do Medicamento. Available at: https://www.janssen.com/brasil/sites/www_janssen_com_brazil/files/prod_files/live/erleada_pub_vp.pdf . Last accessed October 2018.
^[13] European Medicines Agency. Apalutamide CHMP meeting highlights. Available at: https://www.ema.europa.eu/en/news/meeting-highlights-committee-medicinal-products-human-use-chmp-12-15-november-2018. Last accessed November 2018.