- Phase III ARANOTE trial met primary endpoint, significantly
increasing radiological progression-free survival (rPFS) with
NUBEQA plus androgen deprivation therapy (ADT) compared to placebo
plus ADT
- Results were consistent with NUBEQA’s established safety
profile with no new signals observed
- NUBEQA now has positive mHSPC data both with and without
docetaxel based on two pivotal Phase III studies
- Bayer plans to present the pivotal data at a forthcoming
scientific congress and discuss these data with the U.S. Food and
Drug Administration (FDA) for regulatory approval
The Phase III ARANOTE trial, investigating NUBEQA®
(darolutamide) plus androgen deprivation therapy (ADT) in patients
with metastatic hormone-sensitive prostate cancer (mHSPC), has met
its primary endpoint of radiological progression-free survival
(rPFS). NUBEQA plus ADT demonstrated a statistically significant
and clinically meaningful increase in rPFS compared to placebo plus
ADT.
Results were consistent with NUBEQA’s established safety profile
with no new signals observed. Detailed results from this
randomized, double-blind, placebo-controlled trial are planned to
be presented at a forthcoming scientific congress.
NUBEQA is currently indicated in the U.S. for the treatment of
adult patients with mHSPC in combination with docetaxel and for the
treatment of adult patients with non-metastatic
castration-resistant prostate cancer (nmCRPC).1
“We are excited to share the positive results from this Phase
III trial. Following potential regulatory approval, physicians will
be able to tailor NUBEQA treatment plans with or without docetaxel
based on individual patient’s needs,” said Christian Rommel, Ph.D.,
Head of Research and Development at Bayer’s Pharmaceuticals
Division. “Today’s results build on the established efficacy and
tolerability profile of NUBEQA. We are looking forward to future
outcomes of our clinical development program investigating the
compound across multiple prostate cancer stages and
indications.”
Bayer plans to present the pivotal data at a forthcoming
scientific conference and discuss these data with the U.S. FDA
regarding submission for regulatory approval.
About the ARANOTE Trial
The ARANOTE trial (NCT04736199) is a randomized, double-blind,
placebo-controlled Phase III study designed to assess the efficacy
and safety of NUBEQA plus androgen deprivation therapy (ADT) in
patients with metastatic hormone-sensitive prostate cancer (mHSPC).
669 patients were randomized to receive 600mg of NUBEQA twice daily
or matching placebo in addition to ADT.
The primary endpoint of this study is radiological
progression-free survival (rPFS), as measured as the time from the
date of randomization to the date of first documentation of
radiological progressive disease or death due to any cause,
whichever occurs first. Secondary endpoints include overall
survival, time from randomization to the date of death from any
cause, time from randomization to the date of first
castration-resistant event, time to initiation of subsequent
anti-cancer therapy, time to prostate-specific antigen (PSA)
progression, PSA undetectable rates, time to pain progression, and
safety assessments.
About NUBEQA® (darolutamide)1
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.
NUBEQA is being evaluated in a robust clinical development
program, which includes studies across various stages of prostate
cancer, including in the Phase III ARANOTE trial evaluating NUBEQA
plus androgen deprivation therapy (ADT) versus ADT alone for mHSPC,
the ARASTEP Phase III trial evaluating NUBEQA plus ADT versus ADT
alone in HSPC patients with high-risk biochemical recurrence (BCR)
and no evidence of metastatic disease by conventional imaging and a
positive PSMA PET/CT at baseline, as well as in the Australian and
New Zealand Urogenital and Prostate Cancer Trials Group (ANZUP) led
international Phase III co-operative group DASL-HiCaP (ANZUP1801)
trial evaluating NUBEQA as an adjuvant treatment for localized
prostate cancer with very high risk of recurrence. Information
about these trials can be found at www.clinicaltrials.gov.
NUBEQA is currently indicated in the U.S. in combination with
docetaxel and ADT for the treatment of adult patients with mHSPC
and for the treatment of adult patients with non-metastatic
castration-resistant prostate cancer (nmCRPC) with ADT.1
NUBEQA is developed jointly by Bayer and Orion Corporation, a
globally operating Finnish pharmaceutical company.
INDICATIONS
NUBEQA® (darolutamide) is an androgen receptor inhibitor
indicated for the treatment of adult patients with:
- Non-metastatic castration-resistant prostate cancer
(nmCRPC)
- Metastatic hormone-sensitive prostate cancer (mHSPC) in
combination with docetaxel
IMPORTANT SAFETY INFORMATION
NUBEQA® (darolutamide) is an androgen receptor inhibitor
indicated for the treatment of adult patients with:
- Non-metastatic castration-resistant prostate cancer
(nmCRPC)
- Metastatic hormone-sensitive prostate cancer (mHSPC) in
combination with docetaxel
IMPORTANT SAFETY INFORMATION
Warnings & Precautions
Ischemic Heart Disease – In a study
of patients with nmCRPC (ARAMIS), ischemic heart disease occurred
in 3.2% of patients receiving NUBEQA versus 2.5% receiving placebo,
including Grade 3-4 events in 1.7% vs. 0.4%, respectively. Ischemic
events led to death in 0.3% of patients receiving NUBEQA vs. 0.2%
receiving placebo. In a study of patients with mHSPC (ARASENS),
ischemic heart disease occurred in 3.2% of patients receiving
NUBEQA with docetaxel vs. 2% receiving placebo with docetaxel,
including Grade 3-4 events in 1.3% vs. 1.1%, respectively. Ischemic
events led to death in 0.3% of patients receiving NUBEQA with
docetaxel vs. 0% receiving placebo with docetaxel. Monitor for
signs and symptoms of ischemic heart disease. Optimize management
of cardiovascular risk factors, such as hypertension, diabetes, or
dyslipidemia. Discontinue NUBEQA for Grade 3-4 ischemic heart
disease.
Seizure – In ARAMIS, Grade 1-2
seizure occurred in 0.2% of patients receiving NUBEQA vs. 0.2%
receiving placebo. Seizure occurred 261 and 456 days after
initiation of NUBEQA. In ARASENS, seizure occurred in 0.6% of
patients receiving NUBEQA with docetaxel, including one Grade 3
event, vs. 0.2% receiving placebo with docetaxel. Seizure occurred
38 to 340 days after initiation of NUBEQA. It is unknown whether
antiepileptic medications will prevent seizures with NUBEQA. Advise
patients of the risk of developing a seizure while receiving NUBEQA
and of engaging in any activity where sudden loss of consciousness
could cause harm to themselves or others. Consider discontinuation
of NUBEQA in patients who develop a seizure during treatment.
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.
Adverse Reactions
In ARAMIS, serious adverse reactions occurred in 25% of patients
receiving NUBEQA vs. 20% of patients receiving placebo. Serious
adverse reactions in ≥1% of patients who received NUBEQA included
urinary retention, pneumonia, and hematuria. Fatal adverse
reactions occurred in 3.9% of patients receiving NUBEQA vs. 3.2% of
patients receiving placebo. Fatal adverse reactions in patients who
received NUBEQA included death (0.4%), cardiac failure (0.3%),
cardiac arrest (0.2%), general physical health deterioration
(0.2%), and pulmonary embolism (0.2%). The most common adverse
reactions (>2% with a ≥2% increase over placebo), including
laboratory test abnormalities, were increased AST, decreased
neutrophil count, fatigue, increased bilirubin, pain in extremity
and rash. Clinically relevant adverse reactions occurring in ≥2% of
patients treated with NUBEQA included ischemic heart disease and
heart failure.
In ARASENS, serious adverse reactions occurred in 45% of
patients receiving NUBEQA with docetaxel vs. 42% of patients
receiving placebo with docetaxel. Serious adverse reactions in ≥2%
of patients who received NUBEQA with docetaxel included febrile
neutropenia (6%), decreased neutrophil count (2.8%),
musculoskeletal pain (2.6%), and pneumonia (2.6%). Fatal adverse
reactions occurred in 4% of patients receiving NUBEQA with
docetaxel vs. 4% of patients receiving placebo with docetaxel.
Fatal adverse reactions in patients who received NUBEQA included
COVID-19/COVID-19 pneumonia (0.8%), myocardial infarction (0.3%),
and sudden death (0.3%). The most common adverse reactions (≥10%
with a ≥2% increase over placebo with docetaxel) were constipation,
rash, decreased appetite, hemorrhage, increased weight, and
hypertension. The most common laboratory test abnormalities (≥30%)
were anemia, hyperglycemia, decreased lymphocyte count, decreased
neutrophil count, increased AST, increased ALT, and hypocalcemia.
Clinically relevant adverse reactions in <10% of patients who
received NUBEQA with docetaxel included fractures, ischemic heart
disease, seizures, and drug-induced liver injury.
Drug Interactions
Effect of Other Drugs on NUBEQA –
Combined P-gp and strong or moderate CYP3A4 inducers decrease
NUBEQA exposure, which may decrease NUBEQA activity. Avoid
concomitant use.
Combined P-gp and strong CYP3A4 inhibitors increase NUBEQA
exposure, which may increase the risk of NUBEQA adverse reactions.
Monitor more frequently and modify NUBEQA dose as needed.
Effects of NUBEQA on Other Drugs –
NUBEQA inhibits breast cancer resistance protein (BCRP)
transporter. Concomitant use increases exposure (AUC) and maximal
concentration of BCRP substrates, which may increase the risk of
BCRP substrate-related toxicities. Avoid concomitant use where
possible. If used together, monitor more frequently for adverse
reactions, and consider dose reduction of the BCRP substrate.
NUBEQA inhibits OATP1B1 and OATP1B3 transporters. Concomitant
use may increase plasma concentrations of OATP1B1 or OATP1B3
substrates. Monitor more frequently for adverse reactions and
consider dose reduction of these substrates.
Review the Prescribing Information of drugs that are BCRP,
OATP1B1, and OATP1B3 substrates when used concomitantly with
NUBEQA.
For important risk and use information about NUBEQA, please
see the accompanying full Prescribing
Information.
About Metastatic Hormone-Sensitive Prostate Cancer
Prostate cancer is the second most common cancer in men and the
fifth most common cause of cancer death in men worldwide.2 In 2020,
an estimated 1.4 million men were diagnosed with prostate cancer,
including almost 300,000 cases in the U.S., and about 375,000 died
from the disease worldwide.3,4
At the time of diagnosis, most men have localized prostate
cancer, meaning their cancer is confined to the prostate gland and
can be treated with curative surgery or radiotherapy. Upon relapse
when the disease will metastasize or spread, androgen deprivation
therapy (ADT) is the cornerstone of treatment for this
hormone-sensitive disease. Approximately 10% of men will already
present with mHSPC when first diagnosed.5,6,7 Men with metastatic
hormone-sensitive prostate cancer (mHSPC) will start their
treatment with hormone therapy, such as ADT, androgen receptor
inhibitor (ARi) plus ADT or a combination of the chemotherapy
docetaxel and ADT. Despite this treatment, most men with mHSPC will
eventually progress to castration-resistant prostate cancer (CRPC),
a condition with limited survival.
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 includes 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.
About Bayer
Bayer is a global enterprise with core competencies in the life
science fields of health care and nutrition. In line with its
mission, “Health for all, Hunger for none,” the company’s products
and services are designed to help people and the planet thrive by
supporting efforts to master the major challenges presented by a
growing and aging global population. Bayer is committed to driving
sustainable development and generating a positive impact with its
businesses. At the same time, the Group aims to increase its
earning power and create value through innovation and growth. The
Bayer brand stands for trust, reliability and quality throughout
the world. In fiscal 2023, the Group employed around 100,000 people
and had sales of 47.6 billion euros. R&D expenses before
special items amounted to 5.8 billion euros. For more information,
go to www.bayer.com.
© 2024 Bayer BAYER, the Bayer Cross and NUBEQA are registered
trademarks of Bayer.
Forward-Looking
Statements
This release may contain forward-looking statements based on
current assumptions and forecasts made by Bayer management. Various
known and unknown risks, uncertainties and other factors could lead
to material differences between the actual future results,
financial situation, development or performance of the company and
the estimates given here. These factors include those discussed in
Bayer’s public reports which are available on the Bayer website at
www.bayer.com. The company assumes no liability whatsoever to
update these forward-looking statements or to conform them to
future events or developments.
References
- NUBEQA (darolutamide) [Prescribing Information]. Whippany, NJ:
Bayer HealthCare Pharmaceuticals, Inc.; October 2023.
- Hyuna S et al. Ca Cancer J Clin 2021; 71:209–249.
- Prostate Cancer: Statistic. Cancer.Net.
https://www.cancer.net/cancer-types/prostate-cancer/statistics.
Accessed: January 2024.
- American Cancer Society. Cancer Facts & Figures 2024.
Accessed: January 2024.
- Piombino C et al. Cancers (Basel). 2023 Oct
11;15(20):4945.
- Helgstrand JT et al. Cancer. 2018;124(14):2931-2938.
- Buzzoni C et al. Eur. Urol. 2015;68:885–890.
PP-NUB-US-3324
7/24
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Sue Ann Pentecost, Tel + 910.221.6446 Email:
sueann.pentecost@bayer.com