ERLEADA™ (apalutamide), a Next-Generation Androgen Receptor Inhibitor, Lowered Risk of Metastasis or Death in Patients with Non-Metastatic Castration-Resistant Prostate Cancer

On February 8, 2018 The Janssen Pharmaceutical Companies of Johnson & Johnson reported new findings from the Phase 3 SPARTAN clinical trial that showed treatment with ERLEADA, an investigational, next-generation1 androgen receptor inhibitor, decreased risk of metastasis or death by 72 percent and improved median metastasis-free survival (MFS) by more than two years (difference of 24.3 months) in patients with non-metastatic castration-resistant prostate cancer (CRPC) whose prostate specific antigen (PSA) is rapidly rising, compared to placebo (Press release, Johnson & Johnson, FEB 8, 2018, View Source [SID1234523893]). The results were presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Genitourinary Cancers Symposium (ASCO GU) in San Francisco (Abstract #161) and were simultaneously published in The New England Journal of Medicine.

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"While there have been advances in the treatment of prostate cancer over the years, metastatic castration-resistant prostate cancer is still a lethal disease. These compelling results are the first to show that metastases can be delayed in these patients," said Eric Small, M.D. FASCO, Professor of Medicine, and Chief of the Division of Hematology and Oncology at the University of California, San Francisco, and lead SPARTAN study investigator. "These data suggest that apalutamide could potentially be a new standard of care for patients with non-metastatic castration-resistant prostate cancer."

SPARTAN, a Phase 3, randomized, double-blind, placebo-controlled, multicenter study, enrolled 1,207 patients with non-metastatic castration-resistant prostate cancer and was conducted at 332 sites in 26 countries in North America, Europe, Asia-Pacific and Australia. Patients were randomized 2:1 to receive ERLEADA in combination with androgen deprivation therapy (ADT) (n=806), or placebo in combination with ADT (n=401).

ERLEADA in combination with ADT decreased the risk of metastasis or death by 72 percent compared to placebo in combination with ADT (HR = 0.28; 95% CI, 0.23-0.35; P<0.0001).2 The median MFS was 40.5 months for ERLEADA in combination with ADT compared to 16.2 months for placebo in combination with ADT, prolonging MFS by more than two years. MFS benefit was consistently seen across all subgroups of patients.2

"Delaying the metastasis of prostate cancer is critical. Once the cancer starts to spread, the patient’s overall health, well-being and prognosis change drastically," said Peter Lebowitz, M.D., Ph.D., Global Therapeutic Area Head of Oncology at Janssen Research & Development, LLC. "The ERLEADA data presented at ASCO (Free ASCO Whitepaper) GU demonstrate the important impact this medicine can have for patients with prostate cancer. Janssen is committed to addressing unmet needs for treatment across all stages of disease progression with novel combinations and novel therapeutics."

In addition to improving metastasis free survival, ERLEADA in combination with ADT, compared to placebo in combination with ADT, demonstrated clinical improvement across secondary endpoints, with statistically significant improvements in time to metastasis (TTM; median of 40.5 months in the ERLEADA arm compared to median of 16.6 months in the placebo arm) and progression-free survival (PFS; median of 40.5 months in the ERLEADA arm compared to median of 14.7 months in the placebo arm). Treatment with ERLEADA decreased the risk of symptomatic progression by 55 percent compared with placebo (HR=0.45; 95% CI, 0.32-0.63; P<0.0001). ERLEADA was associated with a 30 percent risk reduction of death compared to placebo at this early interim analysis for overall survival (OS).2 In exploratory endpoints, ERLEADA in combination with ADT, compared to placebo in combination with ADT, also achieved a 94 percent risk reduction in time to PSA progression (HR = 0.06; 95% CI, 0.05-0.08; P<0.0001), and a 51 percent risk reduction in second progression-free survival (PFS2). The combination of ERLEADA and ADT was tolerable, with maintenance of overall health-related quality of life.

The most common Grade 3/4 treatment-emergent adverse events (TEAEs) for ERLEADA in combination with ADT versus placebo in combination with ADT were rash (5.2 percent vs. 0.3 percent), fall (1.7 percent vs. 0.8 percent) and fracture (2.7 percent vs. 0.8 percent). Treatment discontinuation due to adverse events were 11 percent in the ERLEADA arm compared to 7 percent in the placebo arm. Rates of serious adverse events (SAEs) were similar in the ERLEADA in combination with ADT arm versus placebo in combination with ADT arm (25 percent vs. 23 percent, respectively).

About Non-Metastatic Castration-Resistant Prostate Cancer
Non-metastatic castration-resistant prostate cancer (CRPC) refers to a disease stage when the cancer no longer responds to medical or surgical treatments that lower testosterone, but has not yet been discovered in other parts of the body using a total body bone scan or CT scan.3 Features include: lack of detectable metastatic disease;3 rapidly rising prostate-specific antigen while on androgen deprivation therapy (ADT) and serum testosterone level below 50 ng/dL.4,5 Ninety percent of patients with non-metastatic CRPC will eventually develop bone metastases, which can lead to pain, fractures and spinal cord compression.6 The relative 5-year survival rate for patients with distant stage prostate cancer is 30 percent.7 While it is critical to delay the onset of metastasis in patients with non-metastatic CRPC, there are currently no FDA approved treatments.

About ERLEADA
ERLEADA (apalutamide) is an investigational, next-generation1 oral androgen receptor (AR) inhibitor that blocks the androgen signaling pathway in prostate cancer cells. ERLEADA inhibits the growth of cancer cells in three ways: by preventing the binding of androgen to the AR; by stopping the AR from entering the cancer cells; and by preventing the AR from binding to the DNA of the cancer cell.