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

By | September 20, 2019

HORSHAM, Pa., Sept. 17, 2019 /PRNewswire/ — 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 For additional study information, visit ClinicalTrials.gov.

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.

* Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V.4.2019. © National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Accessed September 16, 2019. To view the most recent and complete version of the NCCN Guidelines®, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use, or application, and disclaims any responsibility for their application or use in any way.

** Orchiectomy, LHRH agonist, or LHRH antagonist

† The term “castration-naive” is used to define patients who are not on ADT at the time of progression. The NCCN Prostate Cancer Panel uses the term “castration-naive” even when patients have had neoadjuvant, concurrent, or adjuvant ADT as part of radiation therapy provided they have recovered testicular function.

***Standard: Directive statement that an action should (benefits outweigh risks/burdens) or should not (risks/burdens outweigh benefits) be taken based on Grade A or B evidence.

***Evidence Level: A designation indicating the certainty of the results as high, moderate, or low (A, B, or C, respectively) based on AUA nomenclature and methodology.

About the Janssen Pharmaceutical Companies of Johnson & Johnson

At Janssen, we’re creating a future where disease is a thing of the past. We’re the Pharmaceutical Companies of Johnson & Johnson, working tirelessly to make that future a reality for patients everywhere by fighting sickness with science, improving access with ingenuity, and healing hopelessness with heart. We focus on areas of medicine where we can make the biggest difference: Cardiovascular & Metabolism, Immunology, Infectious Diseases & Vaccines, Neuroscience, Oncology, and Pulmonary Hypertension.

Learn more at www.janssen.com. Follow us at www.twitter.com/JanssenGlobal. Janssen Research & Development, LLC and Janssen Biotech, Inc. are part of the Janssen Pharmaceutical Companies of Johnson & Johnson.

Cautions Concerning Forward-Looking Statements
This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding ERLEADA® (apalutamide). The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialize, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, any of the other Janssen Pharmaceutical Companies and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behavior and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 30, 2018, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in the company’s most recently filed Quarterly Report on Form 10-Q, and the company’s subsequent filings with the Securities and Exchange Commission. Copies of these filings are available online at www.sec.gov, www.jnj.com or on request from Johnson & Johnson. Neither the Janssen Pharmaceutical Companies of Johnson & Johnson nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.

  1. 1 ERLEADA® Prescribing Information, September 17, 2019.
    2 Supplement: Scher HI, Solo K, Valant J, Todd MB, Mehra M et al. Prevalence of Prostate Cancer Clinical States and Mortality in the United States: Estimates Using a Dynamic Progression Model. PLoS One. 2015; 10(10):1-2.
    3 Chi, K. Apalutamide for Metastatic, Castration Sensitive Prostate Cancer. New England Journal of Medicine. Accessed September 2019.
    4 American Society of Clinical Oncology. ASCO Answers: Prostate Cancer (2018). http://www.cancer.net/sites/cancer.net/files/asco_answers_guide_prostate.pdf. Accessed September 2019.
    5 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V.4.2019. National Comprehensive Cancer Network, Inc. 2019. All rights reserved. Updated August 2019.
    6 American Urological Association. Castration-Resistant Prostate Cancer Guidelines. http://www.auanet.org/guidelines/castration-resistant-prostate-cancer-(2013-amended-2018). Accessed September 2019.

SOURCE Janssen Pharmaceutical Companies of Johnson & Johnson

Posted: September 2019

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