sNDA submitted to FDA for darolutamide plus ADT in mHSPC

Bayer has submitted a supplemental new drug application (sNDA) to the FDA for darolutamide (Nubeqa) in combination with androgen deprivation therapy (ADT) for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC), the company announced in a news release.¹

According to the release, the sNDA is based on results from the phase 3 ARANOTE trial (NCT04736199), which were recently presented at the 2024 European Society for Medical Oncology Congress in Barcelona, Spain and published in The Journal of Clinical Oncology.^2,3

In study, according to the investigators, “darolutamide significantly reduced the risk of radiological progression or death by 46%” (HR=0.54, 95% CI, 0.41-0.71, P < .0001).²

Fred Saad, CQ, MD, FRCS, FCAHS

“Patients in the darolutamide arm did not reach first [radiological progression-free survival] median, but at 24 months, 70[.3]% had not progressed vs 52[.1]% in the placebo/ADT arm,” reported study investigator Fred Saad, CQ, MD, FRCS, FCAHS, director of Prostate Cancer Research, Montreal Cancer Institute, CRCHUM and professor of surgery at the University of Montreal, Quebec, Canada.

Saad added that all subgroups derived benefit from treatment with darolutamide/ADT. The HR for high-volume disease was 0.60 (95% CI, 0.44-0.80), and the HR for low-volume disease was 0.30 (0.15-0.60).

Treatment-emergent adverse event (TEAE) incidence was found to be similar between the 2 groups, with rates of TEAEs leading to permanent discontinuation of study drug of 6.1% of patients in the darolutamide arm and 9.0% of patients in the placebo/ADT arm.

Discussing secondary end points, Saad said, “The secondary end points, all favored, again, darolutamide. Overall survival, with only about 24 months of follow-up, is still immature and not reached in either arm. But importantly, time to metastatic CRPC…was improved, with a hazard ratio of 0.40 [95% CI, 0.32-0.51], so a 60% reduction in terms of time to mCRPC. And in terms of time to pain progression, there was a 28% advantage in the patients getting darolutamide over placebo.”

In patients receiving darolutamide, 62.6% of patients achieved a prostate-specific antigen (PSA) level of lower than 0.2 ng/mL at any time during treatment vs 18.5% of patients in the placebo/ADT arm. In addition, time to PSA progression was improved by 69% (HR=0.31, 95% CI, 0.23-0.42) in patients receiving darolutamide vs placebo/ADT.

“Simply put, our ambition is to help more patients with prostate cancer,” said Christine Roth, Executive Vice President, Global Product Strategy and Commercialization and Member of the Pharmaceuticals Leadership Team at Bayer, in the news release.¹ “We are proud of the role NUBEQA currently plays in the treatment of mHSPC and with this FDA submission, hope to expand the use of NUBEQA to more patients with the disease, regardless of chemotherapy use.”

Darolutamide is currently FDA approved for the following indications:

• non-metastatic castration-resistant prostate cancer

• mHSPC in combination with docetaxel

REFERENCES

1. 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 September 26, 2024. https://www.businesswire.com/news/home/20240926766866/en/Bayer-Submits-Supplemental-New-Drug-Application-to-U.S.-FDA-Seeking-Expanded-Indication-for-NUBEQA%C2%AE-darolutamide-in-Metastatic-Hormone-Sensitive-Prostate-Cancer

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. Presented at: 2024 European Society for Medical Oncology Congress. September 13-17, 2024. Barcelona, Spain. Abstract LBA68. https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.esmo/static/esmo2024_abstracts/LBA68.html.pdf

3. Saad F, Vjaters E, Shore N, et al. Darolutamide in combination with androgen-deprivation therapy in patients with metastatic hormone-sensitive prostate cancer from the phase III ARANOTE trial. 2024 Sep 16:JCO2401798. doi:10.1200/JCO-24-01798