Newswire (Published: Tuesday, July 30, 2019, 7:20:00 PM CDT, Received: Tuesday, July 30, 2019, 7:20:36 PM CDT)
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"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
"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
"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
In the ARAMIS trial, both arms showed a 9 percent discontinuation rate due to adverse reactions.1 The most frequent adverse reactions requiring discontinuation in patients who received Nubeqa included cardiac failure (0.4 percent), and death (0.4 percent).1 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).1 Nubeqa was not studied in women and there is a warning and precaution for embryo-fetal toxicity.1
Overall survival (OS) and time to pain progression were additional secondary efficacy endpoints.1 OS data were not yet mature at the time of final MFS analysis.1 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.1 Pain progression was reported in 28 percent of all patients on study.1
Bayer has filed for approval of Nubeqa in the
Nubeqa will be available in oral tablets for adults.1 For more information, visit www.NUBEQA.com.
Bayer is committed to ensuring that patients in the
Clinical Trial Results
The FDA approval of Nubeqa® (darolutamide) is based on the ARAMIS trial, a randomized, double-blind, placebo-controlled, multi-center Phase III study, which evaluated the safety and efficacy of oral Nubeqa in patients with nmCRPC who were receiving a concomitant gonadotropin-releasing hormone (GnRH) analog or had a bilateral orchiectomy. In the clinical study, 1,509 patients were randomized in a 2:1 ratio to receive 600 mg of Nubeqa orally twice daily or placebo plus ADT. Patients with a history of seizure were allowed in the study.1
The primary efficacy endpoint of the trial was MFS, defined as the time from randomization to the time of first evidence of BICR-confirmed distant metastasis or death due to any cause within 33 weeks after the last evaluable scan, whichever occurred first.1 Nubeqa plus ADT demonstrated a statistically significant improvement in MFS, with a median MFS of 40.4 months versus 18.4 months with placebo plus ADT [HR=0.41, 95% CI (0.34, 0.50), p<0.0001].1 OS and time to pain progression were additional secondary efficacy endpoints.1 OS data were not yet mature at the time of final MFS analysis.1 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.1 Pain progression was reported in 28 percent of all patients on study.1
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).1 The only observed adverse reaction in ≥10 percent of patients receiving Nubeqa was fatigue.1 Additionally, clinically significant adverse reactions occurring in 2 percent or more of patients treated with Nubeqa included ischemic heart disease (4.0 percent versus 3.4 percent on placebo) and heart failure (2.1 percent versus 0.9 percent on placebo).1 Discontinuation due to adverse reactions occurred in 9 percent of patients in both arms of the study.1 The most frequent adverse reactions requiring discontinuation in patients who received Nubeqa included cardiac failure (0.4 percent), and death (0.4 percent).1 Dose interruptions due to an adverse reaction occurred in 13 percent of patients treated with Nubeqa.1 The most frequent adverse reactions requiring dosage interruption in patients who received Nubeqa included hypertension (0.6 percent), diarrhea (0.5 percent), and pneumonia (0.5 percent).1 Dose reductions due to an adverse reaction occurred in 6 percent of patients treated with Nubeqa.1 The most frequent adverse reactions requiring dosage reduction in patients treated with Nubeqa included fatigue (0.7 percent), hypertension (0.3 percent), and nausea (0.3 percent).1
About Nubeqa® (darolutamide)
Nubeqa® (darolutamide) is an androgen receptor inhibitor (ARi) with a distinct chemical structure that competitively inhibits androgen binding, AR nuclear translocation, and AR-mediated transcription.1 Nubeqa is approved for the treatment of patients with non-metastatic castration-resistant prostate cancer (nmCRPC).1 A Phase III study in metastatic hormone-sensitive prostate cancer (ARASENS) is ongoing. Information about this trial can be found at www.clinicaltrials.gov.
Bayer has submitted filings for darolutamide in the
About Prostate Cancer
Prostate cancer is the second most commonly diagnosed malignancy and fifth leading cause of cancer in men worldwide.7 In 2018, an estimated 1.2 million men were diagnosed with prostate cancer, and about 358,000 died from the disease worldwide.7 Prostate cancer results from the abnormal proliferation of cells within the prostate gland, which is part of a man's reproductive system.8 It mainly affects men over the age of 50, and the risk increases with age.9 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.10 However, in nearly all cases, the cancer eventually becomes resistant to conventional hormone therapy.11
Castration-resistant prostate cancer (CRPC) is an advanced form of the disease where the cancer keeps progressing even when the amount of testosterone is reduced to very low levels in the body. The field of treatment options for castration-resistant patients is evolving rapidly, but until two years ago, there have been no FDA-approved treatment options for CRPC patients who have prostate cancer that has not spread to other parts of the body with rising prostate-specific antigen (PSA) levels despite a castrate testosterone level, which is called non-metastatic castration-resistant prostate cancer, or nmCRPC.6,12 About one-third of men with nmCRPC go on to develop metastases within two years.4 In men with progressive nmCRPC, a short PSA doubling time is correlated with shortened time to first metastasis and death.12
IMPORTANT SAFETY INFORMATION
Embryo-Fetal Toxicity: Safety and efficacy of NUBEQA have not been established in females. NUBEQA can cause fetal harm and loss of pregnancy. Advise males with female partners of reproductive potential to use effective contraception during treatment with NUBEQA and for 1 week after the last dose.
Serious adverse reactions occurred in 25% of patients receiving NUBEQA and in 20% of patients receiving placebo. Serious adverse reactions in ≥ 1 % of patients who received NUBEQA were urinary retention, pneumonia, and hematuria. Overall, 3.9% of patients receiving NUBEQA and 3.2% of patients receiving placebo died from adverse reactions, which included death (0.4%), cardiac failure (0.3%), cardiac arrest (0.2%), general physical health deterioration (0.2%), and pulmonary embolism (0.2%) for NUBEQA.
Adverse reactions occurring more frequently in the NUBEQA arm (≥ 2% over placebo) were fatigue (16% vs. 11%), pain in extremity (6% vs. 3%) and rash (3% vs. 1%).
Clinically significant adverse reactions occurring in ≥ 2% of patients treated with NUBEQA included ischemic heart disease (4.0% vs. 3.4% on placebo) and heart failure (2.1% vs. 0.9% on placebo).
Effect of Other Drugs on NUBEQA – Concomitant use of NUBEQA with a combined P-gp and strong or moderate CYP3A4 inducer decreases darolutamide exposure, which may decrease NUBEQA activity. Avoid concomitant use of NUBEQA with combined P-gp and strong or moderate CYP3A4 inducers.
Concomitant use of NUBEQA with a combined P-gp and strong CYP3A4 inhibitor increases darolutamide exposure, which may increase the risk of NUBEQA adverse reactions. Monitor patients more frequently for NUBEQA adverse reactions and modify NUBEQA dosage as needed.
Effects of NUBEQA on Other Drugs – NUBEQA is an inhibitor of breast cancer resistance protein (BCRP) transporter. Concomitant use of NUBEQA increases the exposure (AUC) and maximal concentration of BCRP substrates, which may increase the risk of BCRP substrate-related toxicities. Avoid concomitant use with drugs that are BCRP substrates where possible. If used together, monitor patients more frequently for adverse reactions, and consider dose reduction of the BCRP substrate drug. Consult the approved product labeling of the BCRP substrate when used concomitantly with NUBEQA.
For important risk and use information about Nubeqa, please see the full Prescribing Information.
About Oncology at Bayer
Bayer is committed to delivering science for a better life by advancing a portfolio of innovative treatments. The oncology franchise at Bayer now expands to six marketed products and several other assets in various stages of clinical development. Together, these products reflect the company's approach to research, which prioritizes targets and pathways with the potential to impact the way that cancer is treated.
Bayer is a global enterprise with core competencies in the life science fields of health care and nutrition. Its products and services are designed to benefit people by supporting efforts to overcome the major challenges presented by a growing and aging global population. At the same time, the Group aims to increase its earning power and create value through innovation and growth. Bayer is committed to the principles of sustainable development, and the Bayer brand stands for trust, reliability and quality throughout the world. In fiscal 2018, the Group employed around 117,000 people and had sales of 39.6 billion euros. Capital expenditures amounted to 2.6 billion euros, R&D expenses to 5.2 billion euros. For more information, go to www.bayer.us.
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This news release may contain forward-looking statements based on current assumptions and forecasts made by
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