Bayer, Orion Announce Expansion of Nubeqa Development Program

Bayer and Orion corporation today announced the upcoming expansion of the global clinical development program for darolutamide (Nubeqa), an oral androgen receptor inhibitor for patients with prostate cancer. A new phase 3 trial, ARANOTE, expected to start patient enrollment by the end of Q1 in 2021, will investigate darolutamide plus androgen deprivation therapy (ADT) vs ADT and placebo in metastatic hormone-sensitive prostate cancer.

Darolutamide was FDA approved in 2019 for patients with nonmetastatic castration-resistant prostate cancer based on results from the ARAMIS trial (NCT02200614), a double-blind, placebo-controlled, multicenter trial that included 1509 patients. Patients were randomized 2:1 to receive either oral darolutamide (600 mg) twice daily or a placebo, and all patients received a gonadotropin-releasing hormone (GnRH) analog concurrently or had a bilateral orchiectomy prior to the study.

The primary end point in the ARAMIS study was metastasis-free survival (MFS), which investigators defined as time from randomization to distant metastasis or death from any cause within 33 weeks after a patient’s last evaluable scan. The study results first published in The New England Journal of Medicine showed median MFS of 40.4 months in the darolutamide cohort (95% CI, 34.3-not reached) vs 18.4 months (95% CI, 15.5-22.3) in the placebo group.

Permanent discontinuation resulting from adverse events was the same in the darolutamide group and the placebo group (9%). Adverse reactions seen more often in the darolutamide cohort than in the placebo group were fatigue (16% compared with 11%), pain in extremities (6% vs 3%), and rash (3% vs 1%).

Overall survival (OS), a secondary end point in the trial, was improved in the experimental group. The darolutamide cohort had a 31% reduction in the risk of death compared with the placebo group—a statistically significant outcome despite 31% of patients in the ADT plus placebo group crossing over to the darolutamide group.

The ARANOTE study will be a phase 3, randomized, double-blind, placebo-controlled study of darolutamide plus ADT vs a placebo and ADT in patients with metastatic hormone-sensitive prostate cancer. The main end point will be radiological progression-free survival, defined as time from randomization to date of first documented radiological progressive disease or death from any cause. Expected enrollment is roughly 555 men, with enrollment anticipated to begin by the end of Q1 2021.

“Nubeqa has already shown in men with non-metastatic castration-resistant prostate cancer that it extends metastasis-free and overall survival,” Scott Z. Fields, MD, senior vice president and head of Oncology Development at Bayer's Pharmaceutical Division, said in a statement. “Given the encouraging results that we have seen with Nubeqa so far, it is important that we also evaluate the potential of Nubeqa in other stages of prostate cancer that may offer men with metastatic hormone-sensitive prostate cancer a new treatment option.”

Reference

FDA approves darolutamide for non-metastatic castration-resistant prostate cancer. FDA. July 20, 2019. Accessed February 8, 2021. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-darolutamide-non-metastatic-castration-resistant-prostate-cancer