On June 4, 2019 The Janssen Pharmaceutical Companies of Johnson & Johnson reported the submission of a Type II variation to the European Medicines Agency (EMA) seeking approval of ERLEADA (apalutamide) for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC), regardless of extent of disease or prior docetaxel treatment history (Press release, Johnson & Johnson, JUN 4, 2019, View Source [SID1234536881]). The submission is based on findings from the Phase 3 TITAN study which were presented at the 2019 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting and simultaneously published online in The New England Journal of Medicine.1,2

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The submission to the EMA follows the submission of supplemental registration dossiers to the U.S. Food and Drug Administration (FDA) on 29th April 2019 and to the Japanese Ministry of Health, Labour and Welfare (MHLW) on 31st May 2019 seeking approval of a new indication for apalutamide for the treatment of patients with mHSPC.3,4

"Today’s application seeking to expand the approval of apalutamide for the treatment of patients with mHSPC marks an important step in our continued focus and commitment to bring innovative medicines forward in the treatment of prostate cancer," said Dr. Joaquín Casariego, Janssen Therapeutic Area Lead Oncology for Europe, Middle East & Africa, Janssen-Cilag S.A. "We look forward to working with the EMA to expand access to this next-generation androgen receptor inhibitor for those patients who may benefit from this treatment in the future."

Results from the Phase 3 TITAN study showed patients with mHSPC, treated with apalutamide plus androgen deprivation therapy (ADT) significantly extended overall survival (OS) compared to placebo plus ADT with a 33 percent reduction in the risk of death (HR=0.67; 95% CI, 0.51-0.89; P=0.0053).2 In both study arms, median OS was not reached.2 Apalutamide plus ADT also significantly improved rPFS compared to placebo plus ADT with a 52 percent reduction in risk of radiographic progression or death compared to placebo plus ADT (HR=0.48; 95% CI, 0.39-0.60; P<0.0001).1 The median rPFS was 22.1 months for placebo plus ADT and not reached for apalutamide plus ADT.2 The two-year OS rates, after a median follow up of 22.7 months, were 82 percent for apalutamide plus ADT compared to 74 percent for placebo plus ADT.2

Adverse events (AEs) were generally consistent with the known apalutamide safety profile. The incidence of Grade 3/4 AEs for apalutamide plus ADT, versus placebo plus ADT were similar (42 percent vs 41 percent).2 The most common Grade ≥3 AEs for apalutamide plus ADT versus placebo plus ADT were hypertension (8.4 percent vs. 9.1 percent) and skin rash (6.3 percent vs. 0.6 percent).2 Additional reported Grade ≥3 AEs for apalutamide plus ADT versus placebo plus ADT were back pain (2.3 percent vs. 2.7 percent), blood alkaline phosphatase increased (0.4 percent vs. 2.5 percent) and anemia (1.7 percent vs. 3.2 percent).2 Treatment discontinuation due to AEs was 8 percent in the apalutamide arm compared to 5 percent in the placebo arm.1 Rash of any grade was more common among patients treated with apalutamide plus ADT, versus placebo plus ADT (27 percent vs 9 percent, respectively).2

In Europe, apalutamide is currently approved for use in adults with non-metastatic castration-resistant prostate cancer (nmCRPC) who are at high risk of developing metastatic disease.5 In the U.S. apalutamide is indicated for the treatment of nmCRPC.6

ENDS

About the TITAN Study1,2

TITAN is a Phase 3 randomised, placebo-controlled, double-blind study in men with mHSPC regardless of extent of disease or prior docetaxel treatment history. The study included 1,052 patients in intention-to-treat (ITT) population in 23 countries across 260 sites in North America, Latin America, South America, Europe and Asia Pacific. Patients with mHSPC were randomised 1:1 and received either apalutamide (240 mg) plus continuous androgen deprivation therapy (ADT) (n=525), or placebo plus ADT (n=527). The recruitment period for the study spanned from December 2015 to July 2017. The study included mHSPC patients with both low- and high-volume disease, those who were newly diagnosed, or those who had received prior definitive local therapy or prior treatment with up to six cycles of docetaxel or up to six months of ADT for mHSPC. Participants were treated until disease progression or the occurrence of unacceptable treatment-related toxicity. An independent data-monitoring committee was commissioned by the sponsor to monitor safety and efficacy before unblinding and make study conduct recommendations. Dual primary endpoints of the study were OS and rPFS. Secondary endpoints included time to cytotoxic chemotherapy, time to pain progression, time to chronic opioid use and time to skeletal-related event. Exploratory endpoints included time to PSA progression, time to second progression-free survival and time to symptomatic progression. For additional study information, visit ClinicalTrials.gov.

About ERLEADA

ERLEADA (apalutamide) is an androgen receptor (AR) inhibitor indicated for use in Europe for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) who are at high risk of developing metastatic disease.5 In the U.S. apalutamide is indicated for the treatment of nmCRPC.6

About Metastatic Hormone-Sensitive Prostate Cancer

Metastatic hormone-sensitive prostate cancer (mHSPC), also referred to as metastatic castration sensitive prostate cancer (mCSPC) refers to prostate cancer that still responds to androgen deprivation therapy (ADT) and has spread to other parts of the body.7 Patients with mHSPC tend to have a poor prognosis, with a median OS of less than five years, underscoring the need for new treatment options.8,9,10