U.S. FDA Approves Updated Prescribing Information for Bayer’s Nubeqa (Darolutamide) in Non-Metastatic Castration-Resistant Prostate Cancer with Overall Survival Benefit

January 12, 2021 /BioonBIOON/ --Bayer(Bayer) recently announced that the U.S. Food and Drug Administration (FDA) has approved a supplemental new drug application (sNDA) for the new prostate cancer drug Nubeqa (darolutamide), adding overall survival (OS) and other secondary endpoint data from the pivotal Phase 3 ARAMIS trial to Nubeqa’s prescribing information.

Data show that in patients with non-metastatic castration-resistant prostate cancer (nmCRPC), Nubeqa significantly reduced the risk of death by 31% and prolonged patient survival compared with placebo. Other endpoints included time to pain progression and time to initiation of cytotoxic chemotherapy. Additional guidance, including information on drug interactions, has also been incorporated into the prescribing information. The final analysis of the extended follow-up, with a median duration of 29 months in the overall study population, further reinforced the safety profile of Nubeqa.

Nubeqa, co-developed by Bayer and the Finnish pharmaceutical company Orion Corporation, has been approved in the United States, the European Union, and many other countries for the treatment of male patients with non-metastatic castration-resistant prostate cancer (nmCRPC). This oral non-steroidal androgen receptor (AR) inhibitor features a unique chemical structure that binds to the receptor with high affinity and exhibits 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.

Senior Vice President of Bayer's Pharmaceutical Division andTumorScott Z. Fields, M.D., Head of Development, stated: “A key goal of cancer treatment is to prolong patient survival while minimizing side effects. Nubeqa has demonstrated efficacy and safety in men with nmCRPC, delaying disease progression in patients who are typically asymptomatic. This update to the prescribing information further reinforces physicians’ confidence in the use of Nubeqa for nmCRPCDiagnosisNubeqa should be prescribed to appropriate patients to help ensure optimal treatment outcomes for these patients.”

ARAMIS is 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 announced data on the primary efficacy endpoint showed: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)., significantly reducing the risk of disease metastasis or death by 59%. However, at the time of the final MFS analysis, the overall survival (OS) data were immature.

The complete results of the final overall survival (OS) analysis of this study were published in The New England Journal of Medicine (NEJM) in September 2020. The results showed that, compared with placebo, Nubeqa significantly prolonged OS, significantly delayed the time to onset of cancer-related symptoms, while minimizing toxicity. (See:Nonmetastatic, Castration-Resistant Prostate Cancer and Survival with Darolutamide）

Specific data are as follows:Compared with placebo + ADT, the Nubeqa + ADT regimen significantly reduced the risk of death by 31% (HR = 0.69; 95% CI: 0.53–0.88; p = 0.003)., whileSignificantly delayed the time to pain progression (HR=0.65, 95% CI: 0.53-0.79; p<0.0001), time to initiation of first cytotoxic chemotherapy (HR=0.58, 95% CI: 0.44-0.76; p<0.0001), and time to first symptomatic skeletal event (SSE), all these secondary endpoints showed statistically significant improvements.

Notably, a statistically significant overall survival (OS) benefit was also observed, despite more than half of the patients in the placebo plus androgen deprivation therapy (ADT) group (55%; 307 out of 554 patients) having crossed over to Nubeqa (31%; 170 patients) or another life-prolonging therapy before the final analysis cutoff date (November 15, 2019).

With a median extended follow-up of 29 months in the overall study population, Nubeqa continued to demonstrate a favorable safety profile. 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), with a low likelihood of 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.

Prostate Cancer (Image source: hopkinsmedicine.org).png

Globally, prostate cancer is the second most common malignancy in menTumoras the fifth leading cause of cancer-related deaths, 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) reducing testosterone levels to very low levels. Approximately one-third of patients with non-metastatic CRPC (nmCRPC) develop metastases within two years; therefore, in this setting, the primary treatment goals 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 has a favorable long-term safety profile, helping patients continue treatment and achieve therapeutic goals.

In addition to nmCRPC, Bayer and Orion Corporation 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: U.S.FDA approves Addition of Overall Survival and Other Secondary Endpoint Data to NUBEQA? (darolutamide) Prescribing Information