Type of information: Positive opinion for the granting of a Market Authorisation in the EU
Product name: Erleada™
Therapeutic area: Cancer - Oncology
- antiandrogen/androgen receptor blocker. Apalutamide is an investigational, next-generation oral androgen receptor inhibitor that inhibits the action of androgen in prostate cancer cells, and prevents binding of androgen to the androgen receptor, and translocation of the androgen receptor to the nucleus of the cancer cell. The compound is acting as a selective competitive antagonist of the androgen receptor.
Company: Janssen Biotech, a J&J company (USA - NJ)
Disease: non-metastatic castration-resistant prostate cancer (CRPC)
- • On November 16, 2018, the Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion, recommending the granting of a marketing authorisation for Erleada™ (apalutamide), intended for the treatment of non-metastatic castration resistant prostate cancer.
- • On February 14, 2018, the FDA has approved
Erleada™ (apalutamide) for the treatment of patients with non-metastatic castration-resistant prostate cancer. This approval follows an FDA Priority Review designation based upon data from the Phase 3 SPARTAN study,
which demonstrated a 72 percent reduction in risk of distant metastasis or death, and an increase in median metastasis-free survival (MFS) by more than two years (difference of
24.31 months) in patients with NM-CRPC. The study was recently presented at the 2018 American Society of Clinical
Oncology Genitourinary Cancers Symposium (ASCO GU) on Thursday, February 8, 2018 in San Francisco and published in The New England Journal of Medicine. SPARTAN enrolled 1,207 patients with non-metastatic castration-resistant prostate cancer. were randomized 2:1 to receive either Erleada™ orally at a dose of 240 mg once daily (n=806), or placebo once daily (n=401). All patients in the SPARTAN trial received a concomitant gonadotropin-releasing hormone (GnRH) analog or had a bilateral orchiectomy. Erleada™ decreased the risk of distant metastasis or death by 72 percent compared to
placebo (HR = 0.28; 95% CI, 0.23-0.35; P<0.0001). The median MFS was 40.51 months for Erleada™ compared to 16.20 months for placebo, prolonging MFS by more than two
years (difference of 24.31 months). MFS benefit was consistently seen across patient subgroups including prostate specific antigen doubling time (PSADT) (?6 months or >6
months), use of a prior bone-sparing agent (yes or no), and locoregional disease (N0 or N1).
- The major efficacy outcome was supported by statistically significant improvements for the following secondary endpoints: time to metastasis (TTM), progression-free survival (PFS) and time to symptomatic progression.4 The median TTM was 40.51 months for Erleada™ compared to 16.59 months for placebo (HR=0.27; 95% CI, 0.22-0.34; P<0.0001) and the median PFS was 40.51 months compared to 14.72 months for placebo (HR=0.29; 95% CI, 0.24-0.36; P<0.0001). Overall survival data were not mature at the time of final MFS analysis (24% of the required number of events).
Warnings and Precautions include seizure, falls and fractures. In the SPARTAN trial, the most common adverse reactions (?10%) were fatigue, hypertension, rash, diarrhea, nausea, weight decreased, arthralgia, fall, hot flush, decreased appetite, fracture, and peripheral edema.
• On February 8, 2018, J&J announced that it has submitted a Marketing Authorisation Application to the European Medicines Agency (EMA) for apalutamide for the treatment of patients with high-risk non-metastatic castration-resistant prostate cancer. The submission is based on data from the pivotal SPARTAN Phase 3 clinical trial which assessed the safety and efficacy of apalutamide versus placebo in men with nmCRPC who have a rapidly rising prostate specific antigen (PSA) level, despite receiving continuous androgen deprivation therapy (ADT).
- • On December 21, 2017, Janssen Biotech announced that the FDA has granted Priority Review designation for the New Drug Application (NDA) for apalutamide, an investigational, next-generation oral androgen receptor (AR) inhibitor for the treatment of men with non-metastatic castration-resistant prostate cancer (CRPC). Currently, there are no FDA -approved treatments for patients with non-metastatic CRPC. The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target date of April 2018 to render a decision on the apalutamide application.
- The NDA submission for apalutamide was completed on October 10, 2017. It is based on Phase 3 data from the pivotal ARN-509-003 (SPARTAN) clinical trial, which assessed the safety and efficacy of apalutamide versus placebo in men with non-metastatic CRPC who have a rapidly rising prostate specific antigen (PSA) despite receiving continuous androgen deprivation therapy.These men with a rapidly rising PSA are at high risk for developing metastatic disease.The primary endpoint of this study was metastasis-free survival (MFS). MFS is the time from randomization to first evidence of confirmed metastasis, or time to death. The SPARTAN study results have been accepted for oral presentation at the ASCO Genitourinary Cancers Symposium on Thursday, February 8, 2018 , in San Francisco .
Submission of marketing authorization application USA : 2017-10-10
Submission of marketing authorization application UE:
Withdrawal of marketing authorization application USA:
Withdrawal of marketing authorization application UE:
US authorization: 2018-02-14
Favourable opinion UE: 2018-11-16
Favourable opinion USA:
Orphan status USA:
Orphan status UE:
Pediatric exclusivit _USA:
Pediatric exclusivity UE: