Skip to main content
Log in

Apalutamide: First Global Approval

Drugs Aims and scope Submit manuscript

Abstract

Apalutamide (ErleadaTM) is a next-generation oral androgen receptor (AR) inhibitor that is being developed by Janssen for the treatment of prostate cancer (PC). It binds directly to the ligand-binding domain of the AR and blocks the effects of androgens. In February 2018, apalutamide received its first global approval in the USA for the treatment of non-metastatic castration-resistant PC (nmCRPC). Apalutamide is undergoing phase III investigation in chemotherapy-naive patients with metastatic CRPC (in combination with abiraterone acetate plus prednisone), patients with high-risk localized or locally advanced PC receiving primary radiation therapy, and in patients with metastatic hormone-sensitive PC and biochemically-relapsed PC. This article summarizes the milestones in the development of apalutamide leading to this first approval in nmCRPC.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

References

  1. Clegg NJ, Wongvipat J, Joseph JD, et al. ARN-509: a novel antiandrogen for prostate cancer treatment. Cancer Res. 2012;72(6):1494–503.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  2. US FDA. ErleadaTM (apalutamide): prescribing information. 2018. https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/210951s000lbl.pdf. Accessed 26 Mar 2018.

  3. Cancian M, Renzulli JF 2nd. Nonmetastatic castration-resistant prostate cancer: a modern perspective. Urology. 2018. https://doi.org/10.1016/j.urology.2018.01.010.

    Article  PubMed  Google Scholar 

  4. Rozet F, Roumeguere T, Spahn M, et al. Non-metastatic castrate-resistant prostate cancer: a call for improved guidance on clinical management. World J Urol. 2016;34(11):1505–13.

    Article  PubMed  CAS  Google Scholar 

  5. Janssen Pharmaceutical Companies of Johnsonson & Johnson. ERLEADA (apalutamide), a next-generation androgen receptor inhibitor, granted U.S. FDA approval for the treatment of patients with non-metastatic castration-resistant prostate cancer [media release]. 2018. https://www.prnewswire.com/news-releases/erleada-apalutamide-a-next-generation-androgen-receptor-inhibitor-granted-us-fda-approval-for-the-treatment-of-patients-with-non-metastatic-castration-resistant-prostate-cancer-300598990.html. Accessed 26 Mar 2018.

  6. Janssen Pharmaceutical Companies of Johnsonson & Johnson. Janssen submits marketing authorisation application for apalutamide to treat patients with high-risk non-metastatic castration-resistant prostate cancer [media release]. 2018. https://www.businesswire.com/news/home/20180209005173/en/Janssen-Submits-Marketing-Authorisation-Application-Apalutamide-Treat. Accessed 26 Mar 2018.

  7. Johnson & Johnson. Johnson & Johnson completes acquisition of aragon pharmaceuticals, Inc. [media release]. 2013. https://www.jnj.com/media-center/press-releases/johnson-johnson-completes-acquisition-of-aragon-pharmaceuticals-inc. Accessed 26 Mar 2018.

  8. Koukourakis MI, Kakouratos C, Kalamida D, et al. Comparison of the effect of the antiandrogen apalutamide (ARN-509) versus bicalutamide on the androgen receptor pathway in prostate cancer cell lines. Anti Cancer Drugs. 2018. https://doi.org/10.1097/CAD.0000000000000592.

    Article  PubMed  Google Scholar 

  9. Joseph JD, Lu N, Qian J, et al. A clinically relevant androgen receptor mutation confers resistance to second-generation antiandrogens enzalutamide and ARN-509. Cancer Discov. 2013;3(9):1020–9.

    Article  PubMed  CAS  Google Scholar 

  10. Rathkopf DE, Smith MR, Ryan CJ, et al. Androgen receptor mutations in patients with castration-resistant prostate cancer treated with apalutamide. Ann Oncol. 2017;28(9):2264–71.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  11. Rathkopf DE, Morris MJ, Fox JJ, et al. Phase I study of ARN-509, a novel antiandrogen, in the treatment of castration-resistant prostate cancer. J Clin Oncol. 2013;31(28):3525–30.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  12. Smith MR, Saad F, Chowdhury S, et al. Apalutamide treatment and metastasis-free survival in prostate cancer. N Engl J Med. 2018. https://doi.org/10.1056/NEJMoa1715546.

    Article  PubMed  PubMed Central  Google Scholar 

  13. Smith MR, Antonarakis ES, Ryan CJ, et al. Phase 2 study of the safety and antitumor activity of apalutamide (ARN-509), a potent androgen receptor antagonist, in the high-risk nonmetastatic castration-resistant prostate cancer cohort. Eur Urol. 2016;70(6):963–70.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. Rathkopf DE, Antonarakis ES, Shore ND, et al. Safety and antitumor activity of apalutamide (ARN-509) in metastatic castration-resistant prostate cancer with and without prior abiraterone acetate and prednisone. Clin Cancer Res. 2017;23(14):3544–51.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Chi KN, Chowdhury S, Radziszewski P, et al. TITAN: a randomized, double-blind, placebo-controlled, phase 3 trial of apalutamide (ARN-509) plus androgen deprivation therapy (ADT) in metastatic hormone-sensitive prostate cancer (mHSPC) [abstract no. 771TiP]. Ann Oncol. 2016;27(Suppl. 6):vi243–65.

  16. Rathkopf DE, Attard G, Efstathiou E, et al. A phase 3 randomized, placebo-controlled double-blind study of ARN-509 plus abiraterone acetate (AA) in chemotherapy-naive metastatic castration-resistant prostate cancer (mCRPC) [abstract no. TPS5071]. J Clin Oncol Conf. 2015;33(15 Suppl.).

  17. McKenzie M, Dearnaley D, Tombal B, et al. ATLAS: a randomized, double-blind, phase 3 study of ARN-509 in patients with high-risk localized or locally advanced prostate cancer receiving primary radiation therapy [abstract no. MP-07.10]. Can Urol Assoc J. 2016;10(5-6 Suppl. 1):S73–4.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Zaina T. Al-Salama.

Ethics declarations

Funding

The preparation of this review was not supported by any external funding.

Conflict of interest

During the peer review process the manufacturer of the agent under review was offered and accepted an opportunity to comment on the article. Changes resulting from any comments received were made by the author on the basis of scientific completeness and accuracy. Zaina T. Al-Salama is a salaried employee of Adis/Springer, is responsible for the article content, and declares no relevant conflicts of interest.

Additional information

This profile has been extracted and modified from the AdisInsight database. AdisInsight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch and beyond.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Al-Salama, Z.T. Apalutamide: First Global Approval. Drugs 78, 699–705 (2018). https://doi.org/10.1007/s40265-018-0900-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s40265-018-0900-z

Navigation