Nubeqa (Darolutamide) Significantly Extends Overall Survival in Men with Non-Metastatic Castration-Resistant Prostate Cancer, Final ARAMIS Trial Data Published in NEJM

September 10, 2020 /Bio ValleyBIOON/ --Bayer(Bayer) recently announced that the complete overall survival (OS) results from the prespecified final OS analysis of the pivotal Phase III ARAMIS study, which evaluated Nubeqa (darolutamide) in patients with non-metastatic castration-resistant prostate cancer (nmCRPC), have been published in the New England Journal of Medicine (NEJM). The results demonstrated that, compared with placebo, Nubeqa significantly prolonged OS and significantly delayed the time to onset of cancer-related symptoms, while minimizing toxicity. (See details:Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide）

Dr. Karim Fizazi, Professor of Medicine at the Gustave Roussy Institute in France and principal investigator of the ARAMIS study, stated, “Through ongoing research, we have identified the need to shift the treatment focus for patients with nmCRPC toward prolonging survival and reducingAdverse Reactionsimportance. These results for Nubeqa are encouraging, and physicians will have greater confidence in tailoring treatment to the diverse needs of patient populations, including improving efficacy, delaying mortality, and enhancing treatment tolerability.”

ARAMIS was a randomized, multicenter, double-blind, placebo-controlled Phase III trial that enrolled 1,509 male patients with non-metastatic castration-resistant prostate cancer (nmCRPC) who were receiving androgen deprivation therapy (ADT) and were at high risk for developing metastatic disease. The study evaluated the efficacy and safety of oral Nubeqa versus placebo. In this study, patients were randomized in a 2:1 ratio to receive either 600 mg of Nubeqa orally twice daily or placebo, concurrently with ADT. Patients with a history of epilepsy were permitted to participate in the study.

Previously reported primary efficacy endpoint data showed that, compared with placebo + ADT, the Nubeqa + ADT regimen significantly prolonged metastasis-free survival (median MFS: 40.4 months vs. 18.4 months; p < 0.0001) and significantly reduced the risk of metastasis or death by 59%. However, at the time of the final MFS analysis, the overall survival (OS) data were immature.

Final OS analysis data published in the NEJM showed that, compared with placebo plus ADT, the Nubeqa plus ADT regimen significantly reduced the risk of death by 31% (HR=0.69; 95% CI: 0.53–0.88; p=0.003), while also significantly delaying time to pain progression, time to initiation of first cytotoxic chemotherapy, and time to first symptomatic skeletal event (SSE). All these secondary endpoints demonstrated statistically significant improvements.

Notably, an overall survival (OS) benefit was also observed, despite more than half of the patients in the placebo plus ADT group (55%, 307 out of 554 patients) having received Nubeqa or other life-prolonging therapies by the final analysis cutoff date (November 15, 2019).

Nubeqa continued to demonstrate a favorable safety profile during an extended median follow-up of 29 months in the overall study population. Compared with earlier analyses, due toAdverse Reactions(AE) The incidence of treatment discontinuation remained unchanged, with 9% of patients in both groups experiencing this outcome.

This latest analysis of the ARAMIS study also confirms that Nubeqa combined with ADT has minimal impact on the central nervous system (CNS) and a low likelihood of causing psychiatric and cognitive disorders. This phenomenon can be explained by the low blood-brain barrier permeability of Nubeqa observed in preclinical studies and healthy individuals.

Nubeqa is an oral non-steroidal androgen receptor (AR) inhibitor with a unique chemical structure that binds to the receptor with high affinity, exhibiting potent antagonistic activity, thereby inhibiting receptor function and the growth of prostate cancer cells. Unlike other existing treatments for nmCRPC, Nubeqa does not cross the blood-brain barrier, resulting in fewer potential drug interactions and central nervous system side effects such as seizures, falls, and cognitive impairment. Currently, Nubeqa has been approved in the European Union, the United States, Australia, Brazil, Canada, and Japan, with applications in other regions either underway or planned.

Nubeqa was developed in collaboration between Bayer and the Finnish pharmaceutical company Orion. Bayer is responsible for the global commercialization of Nubeqa, while Bayer and Orion jointly promote it in certain European markets (such as France, Germany, Italy, Spain, the United Kingdom, Scandinavia, and Finland).

Globally, prostate cancer is the second most common malignancy in menTumorIt is the fifth leading cause of cancer-related death, primarily affecting men over the age of 50, with risk increasing with age. Castration-resistant prostate cancer (CRPC) refers to prostate cancer that continues to progress despite androgen deprivation therapy (ADT) when testosterone levels in the body are reduced to very low levels. Approximately one-third of patients with non-metastatic castration-resistant prostate cancer (nmCRPC) develop metastases within two years; therefore, the primary treatment goals in this setting are to delay metastasis and spread of prostate cancer and to limit treatment-related side effects.

Since men with nmCRPC are typically asymptomatic and lead active lives, it is crucial to have treatment options that can delay cancer progression while minimizing treatment-related side effects, thereby enabling them to maintain their lifestyle with minimal disruption.

Nubeqa will provide an important treatment option for male patients with nmCRPC, significantly extending metastasis-free survival (MFS) and overall survival (OS). The drug demonstrates favorable long-term safety, facilitating continuous treatment adherence and the achievement of therapeutic goals.

In addition to nmCRPC, Bayer and Orion are also advancing another Phase III clinical trial, ARASENS, to evaluate the efficacy and safety of darolutamide in the treatment of metastatic hormone-sensitive prostate cancer (mHSPC). (Bioon.com)

Original Source: New England Journal of Medicine publishes final overall survival data for Nubeqa™ (darolutamide) showing treatment significantly extends life in men with non-metastatic prostate cancer