Bayer Submits New Indication Application for Nubeqa (Darolutamide) in Japan for Metastatic Hormone-Sensitive Prostate Cancer

Prostate Cancer (Image Source: hopkinsmedicine.org)

News on March 24, 2022 /BioValleyBIOON/ --BayerBayer recently announced that it has submitted a new indication application for Nubeqa (generic name: darolutamide) to Japan's Ministry of Health, Labour and Welfare (MHLW):This medication is an orally administered next-generation androgen receptor inhibitor (ARi), used in combination with docetaxel and androgen deprivation therapy (ADT) for the treatment of patients with metastatic prostate cancer.In Japan, Nubeqa has been approved for the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC) patients at high risk of developing metastatic disease.

Earlier this month, Bayer also submitted a new indication application for Nubeqa in the United States and the European Union. These applications are based on the results of the Phase 3 ARASENS trial. Relevant data were presented at the 2022 American ClinicalTumorPresented at the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) and published in the prestigious New England Journal of Medicine (NEJM). For details, see:Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate CancerAccording to the study data, Bayer plans to submit a marketing application for Nubeqa targeting the mHSPC indication to regulatory authorities around the world.

ARASENS is the only randomized, double-blind, pivotal trial with a prospective design aimed at evaluating the second-generation ARi (Nubeqa) in combination with docetaxel and androgen deprivation therapy (ADT) for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC), compared to docetaxel + ADT. (Note: Docetaxel + ADT is the standard-of-care regimen recommended by guidelines.)

The results showed,Compared with the Docetaxel+ADT regimen, the Nubeqa+Docetaxel+ADT regimen significantly extended overall survival (median OS: Not Estimable [NE] vs 48.9 months) and significantly reduced the risk of death by 32.5%.(HR=0.68; 95%CI:0.57-0.80; p<0.001). As of the data cutoff date for the primary analysis (October 25, 2021), the median treatment duration for the Nubeqa + docetaxel + ADT regimen (41.0 months) was longer than that of the docetaxel + ADT regimen (16.7 months). Although patients in the docetaxel + ADT regimen group who entered the follow-up subsequently received systemic anti-TumorThe use of treatments (such as abiraterone, enzalutamide, cabazitaxel, docetaxel, radium chloride [223Ra], sipuleucel-T, lutetium-177 PMSA, apalutamide) has significantly increased, but a significant improvement in OS was still observed in the Nubeqa + docetaxel + ADT regimen group.

Moreover, compared with the Docetaxel+ADT regimen, the Nubeqa+Docetaxel+ADT regimen also demonstrated consistent improvements in secondary endpoints and pre-specified subgroups. Key secondary endpoint data showed a significant delay in the time to development of castration-resistant prostate cancer (CRPC) (HR=0.36; 95% CI: 0.30-0.42; P<0.001), a significant delay in the time to pain progression (HR=0.79; 95% CI: 0.66-0.95; P=0.01), a significant delay in the time to first symptomatic skeletal event (SSE) (HR=0.71; 95% CI: 0.54-0.94; P=0.02), and the initiation of subsequent systemic anti-cancer therapy.TumorTreatment time (HR=0.39, 95%CI:0.33-0.46; P<0.001).

In the study, adding Nubeqa to the docetaxel + ADT regimen did not increase the incidence of adverse events (AEs). The treatment-emergent adverse events (TEAEs) reported in each treatment group were similar.

Darolutamide Molecular Structure (Image Source: Wikipedia)

Globally, prostate cancer is the second most common malignant tumor in men.TumorAnd the fifth leading cause of cancer death, primarily affecting men over 50, with the risk increasing as age advances. In 2020, it was estimated that 1.4 million men globally wereDiagnosisAbout 375,000 men die from prostate cancer. At the time of diagnosis, most men have localized prostate cancer, which means their cancer is confined to the prostate and can be treated with surgery or radiation therapy. When the disease recurs, metastasizes, or spreads, Androgen Deprivation Therapy (ADT) forms the basis for treating this hormone-sensitive condition.

About 5% of men at the firstDiagnosisPatients with prostate cancer accompanied by distant metastases. Male patients diagnosed with metastatic hormone-sensitive prostate cancer (mHSPC) will initiate hormone therapy, such as ADT, androgen receptor inhibitor (ARi) + ADT, docetaxel + ADT, etc. Despite undergoing these treatments, the majority of male patients with mHSPC will eventually progress to castration-resistant prostate cancer (CRPC), a condition associated with limited survival.

Nubeqa, developed by Bayer in collaboration with Finnish pharmaceutical company Orion, has been approved in multiple markets worldwide, including the United States, the European Union, China, and Japan, for the treatment of men with non-metastatic castration-resistant prostate cancer (nmCRPC). Nubeqa provides an important treatment option for men with nmCRPC, significantly extending metastasis-free survival (MFS) and overall survival (OS), while demonstrating a favorable long-term safety profile that supports continuous treatment and helps achieve therapeutic goals.

Nubeqa is an oral next-generation non-steroidal androgen receptor (AR) inhibitor with a unique chemical structure that binds to the receptor with high affinity, exhibiting strong antagonistic activity, thereby inhibiting receptor function and the growth of prostate cancer cells. Unlike other existing nmCRPC treatments, 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, Bayer and Orion are developing Nubeqa for the treatment of mHSPC. In addition to the ARASENS trial, another phase 3 trial (ARANOTE) evaluating the Nubeqa + ADT regimen for mHSPC is ongoing. (Bioon.com)

Source of Original Text:Bayer submits application for additional indication of Nubeqa? (darolutamide) in Japan