EU Approval Sought for Darolutamide Plus ADT for mHSPC

An application seeking a new indication for the oral androgen receptor inhibitor darolutamide (Nubeqa) plus androgen deprivation therapy (ADT) for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC) has been submitted to the European Medicines Agency (EMA), according to a press release from Orion Corporation. The submission comes from Orion’s collaboration partner, Bayer.¹

“Each man with mHSPC has unique needs. It’s crucial to equip physicians with options to tailor treatment plans to the individual, whether that is with or without chemotherapy,” said Christine Roth, executive vice president of Global Product Strategy and Commercialization and member of the Pharmaceuticals Leadership Team at Bayer. “Our ambition is to redefine what it means to live with prostate cancer at different stages of the disease, extending survival and delaying disease progression, while maintaining daily living.”

The pharmaceutical company is seeking the approval of darolutamide for this patient population based on positive results from the pivotal phase 3 ARANOTE trial (NCT04736199).

Updated findings from ARANOTE were presented at the 2024 ESMO Congress and simultaneously published in the Journal of Clinical Oncology. The combination produced a 46% reduction in the risk of radiological progression or death compared with placebo plus ADT in patients with mHSPC (HR, 0.54; 95% CI, 0.41-0.71; P < .0001), meeting the study’s primary end point. Moreover, the 24-month rPFS rates were 70.3% for the darolutamide plus ADT group vs 52.1% for the placebo plus ADT group. The median rPFS was not reached (NR; 95% CI, NR-NR) in the darolutamide arm vs 25.0 months (95% CI, 19.0-NR) in the placebo group.^1,2

Although benefit was observed with the investigative combination across all secondary end points, OS data were immature at the time of analysis.

Overview of ARANOTE

ARANOTE is a randomized, double-blind, placebo-controlled clinical trial that evaluated the efficacy and safety of darolutamide in combination with ADT for patients with mHSPC.2 Eligible patients had an ECOG performance status between 0 and 2, and were randomly assigned 2:1 to 600 mg of darolutamide twice daily plus ADT (n = 446) vs placebo in combination with ADT (n = 223).^2,3

The primary end point of the trial is radiologic progression-free survival (rPFS). Secondary end points included overall survival (OS), time from randomization to the date of first castration-resistant event, time to initiation of subsequent anticancer therapy, time to prostate-specific antigen (PSA) progression, PSA undetectable rates, time to pain progression, and safety.

Additional safety data from ARANOTE showed an overall low incidence of treatment-emergent adverse effects (AEs) across both study arms. Similarly, the incidence of grade 3 and 4 or grade 5 AEs were comparable in both treatment groups. No new safety signals were reported with the darolutamide combination.

Current Indications for Darolutamide

Darolutamide plus ADT and docetaxel is approved for patients with mHSPC in over 80 markets globally.¹

In August 2022, the FDA approved darolutamide treatment in combination with docetaxel for adult patients with mHSPC. This decision was supported by findings from the phase 3 ARASENS trial (NCT02799602).⁴

On September 26, 2024, Bayer announced their submission of a supplemental new drug application to the FDA. This application seeks to expand the indication of darolutamide plus ADT to include patients with mHSPC. The submission was also supported by updated data from ARANOTE.³

References

1. Bayer submits application for third indication of darolutamide in the EU. Press Release. Bayer. October 14, 2024. Accessed October 14, 2024. https://www.bayer.com/media/en-us/bayer-submits-application-for-third-indication-of-darolutamide-in-the-eu/
2. Saad F, Vjaters E, Shore ND, et al. Efficacy and safety of darolutamide plus androgen-deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) from the phase III ARANOTE trial. Ann Oncol. 2024;35(suppl 2):1-72. doi:10.1016/annonc/annonc1623
3. Bayer submits supplemental new drug application to U.S. FDA seeking expanded indication for NUBEQA® (darolutamide) in metastatic hormone-sensitive prostate cancer. News Release. Bayer. September 26, 2024. Accessed October 14, 2024. https://www.bayer.com/en/us/news-stories/expanded-indication-for-nubeqar
4. FDA approves darolutamide tablets for metastatic hormone-sensitive prostate cancer. News. FDA. August 5, 2022. Accessed October 14, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-darolutamide-tablets-metastatic-hormone-sensitive-prostate-cancer