FDA Approves Erleada (apalutamide) for the Treatment of Patients with Metastatic Castration-Sensitive Prostate Cancer (mCSPC)

The Janssen Pharmaceutical Companies of Johnson & Johnson announced today that the U.S. Food and Drug Administration (FDA) has approved Erleada (apalutamide) for the treatment of patients with metastatic castration-sensitive prostate cancer (mCSPC).1 Today's approval follows FDA Priority Review Designation of the supplemental New Drug Application (sNDA) that was submitted in April 2019 and reviewed through the FDA Real-Time Oncology Review program. The new indication for Erleada will make this androgen receptor inhibitor available for the approximately 40,000 people in the U.S. diagnosed with mCSPC annually.2

Approval is based on results from the Phase 3 TITAN study, which achieved statistical significance in the dual primary endpoints of overall survival (OS) and radiographic progression-free survival (rPFS) at the first pre-planned interim analysis.3 The trial recruited patients regardless of extent of disease, including both high- and low- volume disease, or prior docetaxel treatment history.1,3 Results were presented in an oral session at the 2019 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in The New England Journal of Medicine.

"Prostate cancer is more difficult to treat once it spreads, and for patients with castration-sensitive disease, it is clear that androgen deprivation therapy (ADT) alone, is often not enough," said Dr. Kim Chi, Medical Oncologist at BC Cancer - Vancouver and principal investigator of the TITAN study. "Results from the TITAN study showed that, regardless of the extent of disease, patients with metastatic castration-sensitive prostate cancer have the potential to benefit from treatment with apalutamide in addition to ADT."

In the TITAN study, Erleada plus ADT significantly extended OS compared to placebo plus ADT with a 33 percent reduction in the risk of death (HR=0.67; 95 percent CI, 0.51-0.89; P=0.0053).1 Erleada plus ADT also significantly improved rPFS compared to placebo plus ADT with a 52 percent lower risk of radiographic progression or death (HR=0.48; 95 percent CI, 0.39-0.60; P<0.0001).1 As reported in the published results from the TITAN study, the two-year OS rates, after a median follow-up of 22.7 months, were 84 percent for Erleada  plus ADT compared to 78 percent for placebo plus ADT.3

"Erleada has the potential to change how patients with prostate cancer are treated, regardless of the extent of the disease or prior docetaxel treatment history, by delaying disease progression and prolonging survival," said Margaret Yu, M.D., Vice President, Prostate Cancer Disease Area Leader, Janssen Research & Development, LLC. "This milestone highlights Janssen's commitment to improve the standard of care for patients with prostate cancer as we continue to develop innovative treatments across the disease continuum."

The most common adverse reactions (≥10 percent) that occurred more frequently in Erleada treated patients (≥2 percent over placebo) from the randomized placebo-controlled clinical trials (TITAN and SPARTAN) were fatigue, arthralgia, rash, decreased appetite, fall, weight decreased, hypertension, hot flush, diarrhea, and fracture.1

About the TITAN Study

TITAN (NCT02489318) is a Phase 3, randomized, placebo-controlled, double-blind study in patients with mCSPC. The study included 1,052 patients in 23 countries across 260 sites in North America, Latin America, South America, Europe, and Asia Pacific. Patients with mCSPC were randomized 1:1 and received either Erleada (240 mg) plus ADT (n=524), or placebo plus ADT (n=527). The recruitment period for the study spanned from December 2015 to July 2017.1 The study included patients with mCSPC with both low- and high-volume disease, and those who were newly diagnosed, or those who had received prior definitive local therapy or prior treatment with up to six cycles of docetaxel for mCSPC.3

An Independent Data-Monitoring Committee was commissioned by the sponsor to monitor safety and efficacy.3 Dual primary endpoints of the study were OS and rPFS.1 Secondary endpoints included time to cytotoxic chemotherapy, time to pain progression, time to chronic opioid use, and time to skeletal-related event.3 Exploratory endpoints included time to PSA progression, PFS2 and time to symptomatic progression.3 

About Metastatic Castration-Sensitive Prostate Cancer

Metastatic castration-sensitive prostate cancer (mCSPC), also known as metastatic hormone-sensitive prostate cancer (mHSPC), refers to prostate cancer that still responds to ADT and has spread to other parts of the body.4  

About Erleada

Erleada (apalutamide) is an androgen receptor (AR) inhibitor indicated for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) and for the treatment of patients with mCSPC. Erleadareceived FDA approval for nmCRPC on February 14, 2018 and was approved for mCSPC on September 17, 2019.1  Erleada is taken orally, once daily, with or without food.1 The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer include apalutamide (Erleada) as a treatment option for patients with non-metastatic (M0) CRPC with a Category 1 recommendation for those with a PSA doubling time ≤10 months.*5 The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) include apalutamide (ERLEADA®) with androgen deprivation** as a Category 1 treatment option for patients with metastatic (M1) castration-naive prostate cancer.†5 The American Urological Association (AUA) Guidelines for Castration-Resistant Prostate Cancer (CRPC) recommend clinicians offer apalutamide (Erleada) with continued androgen deprivation therapy (ADT) as one of the treatment options for patients with nmCRPC at high risk for developing metastatic disease. (Standard; Evidence Level Grade A)***.6 Erleada is being studied in five Phase 3 clinical trials.

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