FDA approves Bayer’s Nubeqa (darolutamide), a new treatment for men with non-metastatic castration-resistant prostate cancer

The U.S. Food and Drug Administration (FDA) approved Nubeqa (darolutamide), an androgen receptor inhibitor (ARi), for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC). The FDA approval is based on the Phase III ARAMIS trial evaluating Nubeqa plus androgen deprivation therapy (ADT), which demonstrated a highly significant improvement in the primary efficacy endpoint of metastasis-free survival (MFS), with a median of 40.4 months versus 18.4 months for placebo plus ADT (p<0.0001).1 MFS is defined as the time from randomization to the time of first evidence of blinded independent central review (BICR)-confirmed distant metastasis or death from any cause within 33 weeks after the last evaluable scan, whichever occurred first. Nubeqa was approved under the FDA’s Priority Review designation, which is reserved for medicines that may provide significant improvements in the safety or effectiveness of the treatment for serious conditions.

“Patients at this stage of prostate cancer typically don’t have symptoms of the disease. The overarching goals of treatment in this setting are to delay the spread of prostate cancer and limit the burdensome side effects of therapy,” said Matthew Smith, M.D., Ph.D., Director of the Genitourinary Malignancies Program, Massachusetts General Hospital Cancer Center. “This approval marks an important new option for the prostate cancer community.”

In the U.S., over 73,000 men are estimated to be diagnosed with castration-resistant prostate cancer (CRPC) in 2019.2 About 40 percent of these patients have prostate cancer that has not spread to other parts of the body and is also associated with a rising prostate-specific antigen (PSA) level, despite a castrate testosterone level, which is known as nmCRPC.2,3 This is important because about one-third of men with nmCRPC go on to develop metastases within two years.4 PSA monitoring is important to identify patients and help offset undertreatment in men before the disease spreads.

“We know that men with nmCRPC are still in the prime of their lives and are at a critical point in their disease when action needs to be taken,” said Howard R. Soule, Ph.D., Executive Vice President and Chief Science Officer, Prostate Cancer Foundation (PCF). “For 26 years, PCF has been focused on research aimed at improving patient outcomes and we welcome the addition of new treatment options that provide men with more choices when working with their doctor to select what’s right for them.”

“With the approval of Nubeqa, we now have a new therapy that extends MFS and allows physicians greater flexibility to treat men living with nmCRPC,” said Robert LaCaze, Member of the Executive Committee of Bayer’s Pharmaceuticals Division and Head of the Oncology Strategic Business Unit at Bayer. “Bayer is proud to take this latest step forward in the nmCRPC treatment landscape. Nubeqa is the newest addition to our prostate cancer portfolio and reflects Bayer’s commitment to finding treatments for men at different stages along the prostate cancer continuum.”

In the ARAMIS trial, both arms showed a 9 percent discontinuation rate due to adverse reactions. The most frequent adverse reactions requiring discontinuation in patients who received Nubeqa included cardiac failure (0.4 percent), and death (0.4 percent). Adverse reactions occurring more frequently in the Nubeqa arm (≥2 percent over placebo) were fatigue (16 percent versus 11 percent), pain in extremity (6 percent versus 3 percent) and rash (3 percent versus 1 percent). Nubeqa was not studied in women and there is a warning and precaution for embryo-fetal toxicity.

Overall survival (OS) and time to pain progression were additional secondary efficacy endpoints. OS data were not yet mature at the time of final MFS analysis. The MFS result was supported by a delay in time to pain progression, defined as at least a 2-point worsening from baseline of the pain score on Brief Pain Inventory-Short Form or initiation of opioids, in patients treated with Nubeqa as compared to placebo. Pain progression was reported in 28 percent of all patients on study.

Bayer has filed for approval of Nubeqa in the European Union (EU), Japan, and with other health authorities. Nubeqa is developed jointly by Bayer and Orion Corporation, a globally operating Finnish pharmaceutical company.