On March 30, 2020 Bayer reported that Nubeqa (darolutamide) receives EU approval as a new treatment for men with non-metastatic castration-resistant prostate cancer (Press release, Bayer, MAR 30, 2020, View Source [SID1234555995]).

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The European Commission has granted marketing authorisation in the European Union (EU) for Nubeqa (darolutamide), an oral androgen receptor inhibitor (ARi). The approval is based on Phase III ARAMIS trial results showing a statistically significant improvement in metastasis-free survival (MFS) for darolutamide plus androgen deprivation therapy (ADT) versus placebo plus ADT, and a favorable safety profile.

The compound, which is developed jointly by Orion Corporation and Bayer, is indicated for the treatment of men with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease. Bayer is responsible for global commercialisation of darolutamide, with a co-promotion of Bayer and Orion in certain European markets, e.g. France, Germany, Italy, Spain, the UK, Scandinavia and Finland.

Nubeqa has a distinct chemical structure which inhibits the growth of prostate cancer cells while limiting the burden of side effects on patients’ everyday lives. The EU approval is based on the pivotal Phase III ARAMIS trial data evaluating the efficacy and safety of darolutamide plus androgen deprivation therapy (ADT) compared to placebo plus ADT. Results demonstrated a highly significant improvement in the primary efficacy endpoint of metastasis-free survival (MFS) of darolutamide plus ADT, with a median of 40.4 months, versus 18.4 months for placebo plus ADT (p<0.001), and a favorable safety profile. Nubeqa is already approved in the U.S., Australia, Brazil, Canada, as well as Japan and filings in other regions are underway or planned by Bayer.

"As men with nmCRPC typically have no symptoms and are leading active lives, it is important to have treatment options that delay the progression of their cancer while minimising the burdensome side effects of treatment, allowing them to maintain their lifestyle with little disruption. Darolutamide provides a welcome new option with a favorable safety profile that helps patients to stay on therapy and allows us to meet these treatment goals," said Karim Fizazi, M.D., Ph.D., Professor of Medicine at the Institut Gustave Roussy, Villejuif, France.

Prostate cancer that is confined to the prostate region and is treated with ADT but keeps progressing, even when the amount of testosterone is reduced to very low levels in the body, is known as nmCRPC. In Europe over 67,000 men are estimated to have a CRPC diagnosis, based on 2018 prostate cancer incidence numbers. About one-third of men with nmCRPC go on to develop metastases within two years.

"We are pleased to collaborate with Bayer in combining our expertise in the development of Nubeqa and look forward to our co-promotion in Europe to support patients with non-metastatic castration-resistant prostate cancer and their healthcare professionals", said Satu Ahomäki, Senior Vice President, Commercial Operations of Orion Corporation.

"The approval of Nubeqa in Europe supports our commitment to delivering innovative medicines that are differentiated from current options and that address unmet medical needs, improve treatment outcomes and maintain quality of life for men at all stages of the prostate cancer continuum," said Robert LaCaze, Member of the Executive Committee of Bayer’s Pharmaceuticals Division and Head of the Oncology Strategic Business Unit. "We expect to report results from the pre-planned OS analysis at an oncology meeting later this year."

In the ARAMIS trial, overall survival (OS) and time to pain progression were additional secondary efficacy endpoints. At the time of final MFS analysis, a positive trend in OS was observed; OS data were not yet mature. Results from the pre-planned final OS analysis are expected to be presented at an upcoming scientific meeting in 2020. The MFS result was additionally supported by a delay in time to pain progression as compared to placebo plus ADT. All other secondary endpoints, time to cytotoxic chemotherapy, and time to a symptomatic skeletal event (SSE), also demonstrated a benefit in favor of darolutamide at the time of final MFS analysis.

Darolutamide plus ADT has demonstrated a favorable safety profile. The most frequent adverse reactions in the darolutamide plus ADT arm, that occurred with an absolute increase in frequency of ≥2% compared to placebo plus ADT, were fatigue/asthenic conditions (16% vs. 11%), pain in extremity (6% vs. 3%), and rash (3% vs. 1%). Discontinuation due to adverse events occurred in 9% of patients in both arms of the study.

About the ARAMIS trial
The ARAMIS trial is a randomized, Phase III, multi-center, double-blind, placebo-controlled trial evaluating the safety and efficacy of oral darolutamide in patients with nmCRPC who are currently being treated with ADT and are at high risk for developing metastatic disease. In the clinical study, 1,509 patients were randomized in a 2:1 ratio to receive 600 mg of darolutamide orally twice daily or placebo along with ADT. Patients with a history of seizure were allowed in the study.

About Nubeqa (darolutamide)
Darolutamide was approved in March 2020 in the European Union under the brand name Nubeqa for the treatment of men with non-metastatic castration-resistant prostate cancer (nmCRPC), who are at high risk of developing metastatic disease. Nubeqa has also received regulatory approval in the U.S., Australia, Brazil, Canada as well as Japan, and filings in other regions are underway or planned by Bayer.

Nubeqa is an oral androgen receptor inhibitor (ARi) with a distinct chemical structure that binds to the receptor with high affinity and exhibits strong antagonistic activity, thereby inhibiting the receptor function and the growth of prostate cancer cells. Darolutamide is also being investigated in a Phase III study in metastatic hormone-sensitive prostate cancer (ARASENS trial). Information about these trials can be found at www.clinicaltrials.gov.

About castration-resistant prostate cancer (CRPC)
Prostate cancer is the second most commonly diagnosed malignancy in men worldwide. In 2018, an estimated 1.2 million men were diagnosed with prostate cancer, and about 358,000 died from the disease worldwide. Prostate cancer is the fifth leading cause of death from cancer in men. Prostate cancer results from the abnormal proliferation of cells within the prostate gland, which is part of a man’s reproductive system. It mainly affects men over the age of 50, and the risk increases with age.

Treatment options range from surgery to radiation treatment to therapy using hormone-receptor antagonists, i.e., substances that stop the formation of testosterone or prevent its effect at the target location. However, in nearly all cases, the cancer eventually becomes resistant to conventional hormone therapy.

CRPC is an advanced form of the disease where the cancer keeps progressing despite ADT treatment, even when the amount of testosterone is reduced to very low levels in the body. In men with progressive nmCRPC, a rapid prostate specific antigen (PSA) doubling time has been consistently associated with reduced time to first metastasis and death.