Developers Submit Supplemental NDA for Darolutamide/ADT in mHSPC

The submission is based on results from the phase 3 ARANOTE trial (NCT04736199), which have been published in the Journal of Clinical Oncology.

A supplemental new drug application has been submitted to the FDA for darolutamide (Nubeqa) plus androgen deprivation therapy (ADT) for patients with metastatic hormone-sensitive prostate cancer, according to a press release from the developer, Orion.¹

The submission is based on results from the phase 3 ARANOTE trial (NCT04736199), which have been published in the Journal of Clinical Oncology.² Darolutamide plus ADT and docetaxel is approved for this population in several markets across the world and for those with non-metastatic castration-resistant prostate cancer who may be at risk for developing metastatic disease.

“This is a historic achievement for Orion and yet another proof of the high-quality research and development work we have been doing for years. With the current track record, the future of darolutamide looks bright. In addition, our clinical pipeline as well as our research pipeline have improved recently. With that, we are increasing the probability to be able to commercialize new innovative medicines in the future to address the various unmet needs of patients”, Liisa Hurme, president and chief executive officer at Orion Corporation, said in the press release.¹

A total of 669 patients were randomly assigned to either the darolutamide combination arm (n = 446) or the placebo plus ADT arm (n = 223). The median patient age was 70 years old, 31.2% were Asian, 49.8% had an ECOG performance status of 0, and 68.3% had a Gleason score of 8 or higher.

At baseline, the median prostate specific antigen was 21.3 ng/mL, 72.5% had de novo metastatic disease, and 12.0% had visceral metastases by central review. The median treatment duration was 24.2 months in the darolutamide arm and 17.3 months in the placebo arm. Of note, 53.8% of patients were still receiving study treatment at the time of analysis vs 28.3%.

Regarding the primary end point of radiological progression-free survival (rPFS), 28.7% in the darolutamide arm had an event vs 42.2% in the placebo arm. rPFS was significantly improved in the darolutamide arm by 46% vs the placebo arm (HR, 0.54; 95% CI, 0.41-0.71; P <.0001). In the combination arm, the median rPFS was not reached vs 25.0 months in the placebo arm. Additionally, rPFS rates at 24 months were 70.3% vs 52.1%, respectively.

The secondary end point of overall survival (OS) showed a benefit in the combination arm vs the placebo arm (HR, 0.81; 95% CI, 0.59-1.12). At 24 months, the OS rates were 79.8% vs 75.5% between each group. Longer time to castration-resistant prostate cancer (HR, 0.40; 95% CI, 0.32-0.51) and PSA progression (HR, 0.31; 95% CI, 0.23-0.41) were observed with darolutamide.

Time to initiation of subsequent anticancer therapy (HR, 0.40; 95% CI, 0.29-0.56) and time to pain progression (HR, 0.72; 95% CI, 0.54-0.96) were also delayed in the darolutamide arm.

The most common adverse effects (AEs) observed were grade 1/2 with rates of 55.5% in the darolutamide arm and 54.3% in the placebo arm. Grade 3/4 AEs were observed in 30.8% and 30.3%, respectively. Grade 5 AEs occurred in no more than 2 patients across each group. Serious AEs occurred in 23.6% of patients in the darolutamide group vs 23.5% in the placebo group. Treatment discontinuation due to AEs occurred in 6.1% vs 9.0%, respectively.

AEs exceeding an incidence of 10% in the darolutamide group included anemia, arthralgia, and urinary tract infection. Investigators did not notice a difference between treatment groups for heart failure, higher incidences of fatigue, cerebral ischemia, diabetes mellitus, and hyperglycemia.

References

1. Orion’s collaboration partner Bayer submits application to U.S. FDA for third indication of darolutamide which has become the first ever Orion-originated blockbuster. News release. Orion. September 26, 2024. Accessed September 26, 2024. https://shorturl.at/Yuuna
2. 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. J Clin Oncol. 2024. doi.10.1200/JCO-24-01798