IN nmCRPC, NUBEQA SIGNIFICANTLY IMPROVED MFS AND OS

nmCRPC

NUBEQA helped men live >2x longer without cancer spreading vs ADT alone¹

Significant increase in primary endpoint metastasis-free survival vs ADT alone

Graph showing the probability of MFS with NUBEQA + ADT vs ADT alone from the ARAMIS study

*95% CI: 34.3-NE.

†95% CI: 15.5-22.3.

ADT=androgen deprivation therapy; CI=confidence interval; HR=hazard ratio; MFS=metastasis-free survival; NE=not estimable; nmCRPC=non-metastatic castration-resistant prostate cancer.

An elderly man standing on beach and smiling

Consistent results for MFS across patient subgroups:
- PSADT (≤6 months or >6 months)
- Prior use of bone-targeting agents (yes or no)

ARAMIS Safety Results

In nmCRPC, NUBEQA reduced risk of death by >30% vs ADT alone^1,2

Statistically significant secondary endpoint: overall survival

Graph showing risk of death with NUBEQA and ADT vs ADT alone from the ARAMIS study

^‡Median (months) NR; 95% CI: 56.1-NR.

^§Median (months) NR; 95% CI: 46.9-NR.

NUBEQA + ADT delayed time to pain progression by 14.9 months over ADT alone^1,2

Statistically significant delay in time to pain progression

SECONDARY ENDPOINT: HR: 0.65; 95% CI: 0.53-0.79;
P<0.0001 (intent to treat)

35% RISK REDUCTION in time to pain progression with NUBEQA + ADT vs ADT alone

Time to pain progression between NUBEQA (darolutamide) + ADT and ADT alone

Time to pain progression was defined as at least a 2-point worsening from baseline of pain score on the BPI-SF
(a validated health-related quality-of-life instrument) or initiation of opioids and reported in 28% of all patients on study^1,2

Postpone cytotoxic chemotherapy for more time before starting chemo^1,2

Significantly delayed time to chemotherapy

SECONDARY ENDPOINT: HR: 0.58; 95% CI: 0.44-0.76;
P<0.001 (intent to treat)

42% RISK REDUCTION in time to initiation of cytotoxic chemotherapy with NUBEQA + ADT vs ADT alone at the final analysis²

Percentage of patients who did not receive cytotoxic chemotherapy at 3 years with Nubeqa + ADT at 83% (n=792) vs ADT alone at 75% (n=416)

Median: NE for both NUBEQA + ADT (N=955) and ADT alone (N=554).

Select exploratory endpoint: time to PSA progression³

These exploratory data are descriptive in nature and are not powered to determine statistical significance

PSA is not a reliable surrogate for overall survival. PSA evaluation should be viewed in the context of patient management and the overall physical condition and clinical course of the patient.

Exploratory endpoint: progression in NUBEQA (darolutamide) + ADT patients in the ARAMIS study

^||95% CI: 25.9-NR.³
^¶95% CI: 3.9-7.4.³

ADT=androgen deprivation therapy; CI=confidence interval; HR=hazard ratio; NE=not estimable; nmCRPC=non-metastatic castration-resistant prostate cancer; NR=not reached; PSA=prostate-specific antigen.

Twice-daily dosing of NUBEQA 600 mg in patients with nmCRPC resulted in undetectable PSA levels in 24% of patients at 12 months compared to 0.4% of patients in the placebo arm¹

OTHER EXPLORATORY ENDPOINTS

Exploratory endpoint results^2,3

Chart with exploratory endpoint results of NUBEQA (darolutamide) + ADT and ADT alone

^#Median: 36.8 mo, NUBEQA + ADT; 14.8 mo, ADT alone.³

**Median: 33.2 mo, NUBEQA + ADT; 7.3 mo, ADT alone.³

^††Median: NE for both NUBEQA + ADT and ADT alone.³

CHOOSE NUBEQA FOR YOUR PATIENTS WITH nmCRPC

Practice Resources

ADT=androgen deprivation therapy; BPI-SF=Brief Pain Inventory-Short Form; CI=confidence interval; HR=hazard ratio; MFS=metastasis-free survival; NE=not estimable; nmCRPC=non-metastatic castration-resistant prostate cancer; OS=overall survival; PSA=prostate-specific antigen; PSADT=prostate-specific antigen doubling time.

ARAMIS Safety Results

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Indications

NUBEQA is an androgen receptor inhibitor indicated for the treatment of adult patients with:

non-metastatic castration resistant prostate cancer (nmCRPC)
metastatic castration-sensitive prostate cancer (mCSPC)
metastatic castration-sensitive prostate cancer (mCSPC) in combination with docetaxel

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Important Safety Information

Warnings & Precautions

Ischemic Heart Disease – Ischemic heart disease, including fatal cases, occurred in patients receiving NUBEQA.

In a pooled analysis of ARAMIS and ARANOTE, ischemic heart disease occurred in 3.4% of patients receiving NUBEQA and 2.2% receiving placebo, including Grade 3-4 events in 1.4% and 0.3%, respectively. Ischemic events led to death in 0.4% of patients receiving NUBEQA and 0.4% receiving placebo.

In ARASENS, ischemic heart disease occurred in 3.2% of patients receiving NUBEQA with docetaxel and 2% receiving placebo with docetaxel, including Grade 3-4 events in 1.3% and 1.1%, respectively. Ischemic events led to death in 0.3% of patients receiving NUBEQA with docetaxel and 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 – Seizure occurred in patients receiving NUBEQA.

In a pooled analysis of ARAMIS and ARANOTE, Grade 1-3 seizure occurred in 0.2% of patients receiving NUBEQA. Seizure occurred from 261 to 665 days after initiation of NUBEQA.

In ARASENS, seizure occurred in 0.8% of patients receiving NUBEQA with docetaxel, including two Grade 3 events. Seizure occurred from 38 to 1754 days after initiation of NUBEQA.

It is unknown whether anti-epileptic 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 – The 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 and in 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 and 3.2% of patients receiving placebo. Fatal adverse reactions that occurred in ≥2 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 (>2% with a ≥2% increase compared to placebo) adverse reactions, including laboratory test abnormalities, were increased AST (23%), decreased neutrophil count (20%), fatigue (16%), increased bilirubin (16%), pain in extremity (6%), and rash (4%). Clinically relevant adverse reactions occurring in 2% or more of patients treated with NUBEQA included ischemic heart disease (4%) and heart failure (2.1%).

In ARANOTE, serious adverse reactions occurred in 24% of patients receiving NUBEQA. Serious adverse reactions in ≥1% of patients who received NUBEQA included pneumonia (2%), urinary tract infection (1.8%), musculoskeletal pain (1.6%), hemorrhage (1.6%), arrhythmias (1.3%), and spinal cord compression (1.1%). Fatal adverse reactions occurred in 4.7% of patients receiving NUBEQA and those that occurred in ≥2 patients included sepsis (1.1%), craniocerebral injury (0.4%), and myocardial infarction (0.4%). The most common (≥10% with a ≥2% increase compared to placebo) adverse reaction is urinary tract infection (12%). The most common laboratory test abnormalities (≥15% with a ≥5% increase over placebo) are increased AST (32%), increased ALT (28%), increased bilirubin (17%), and decreased neutrophil count (16%). Clinically relevant adverse reactions in <10% of patients who received NUBEQA included arrhythmia (8.8%), pneumonia (3.6%), and myocardial infarction (0.7%).

In ARASENS, serious adverse reactions occurred in 45% of patients receiving NUBEQA with docetaxel. Serious adverse reactions in ≥2% of patients who received NUBEQA with docetaxel included febrile neutropenia (6%), neutrophil count decreased (2.8%), musculoskeletal pain (2.6%) and pneumonia (2.6%). Fatal adverse reactions occurred in 4% of patients receiving NUBEQA with docetaxel. Fatal adverse reactions in ≥2 patients who received NUBEQA included COVID-19/COVID-19 pneumonia (0.8%), myocardial infarction (0.3%), and sudden death (0.3%). The most common (≥10% with a ≥2% increase over placebo with docetaxel) adverse reactions are constipation (23%), rash (20%), decreased appetite (19%), hemorrhage (18%), increased weight (18%), and hypertension (14%). The most common laboratory test abnormalities (≥30%) are anemia (72%), hyperglycemia (57%), decreased lymphocyte count (52%), decreased neutrophil count (49%), increased AST (40%), increased ALT (37%), and hypocalcemia (31%). Clinically relevant adverse reactions in <10% of patients who received NUBEQA with docetaxel included fractures (8%), ischemic heart disease (3.2%), seizures (0.6%), and drug-induced liver injury (0.3%).

Drug Interactions

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 BCRP transporter. Concomitant use of NUBEQA increases the AUC and C_max 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.

NUBEQA is an inhibitor of OATP1B1 and OATP1B3 transporters. Concomitant use of NUBEQA may increase the plasma concentrations of OATP1B1 or OATP1B3 substrates. Monitor patients more frequently for adverse reactions of these drugs and consider dose reduction while patients are taking NUBEQA.

Review the Prescribing Information of drugs that are BCRP, OATP1B1, and OATP1B3 substrates when used concomitantly with NUBEQA.

Please see the full Prescribing Information.

You are encouraged to report side effects or quality complaints of products to the FDA by visiting www.fda.gov/medwatch or calling 1-800-FDA-1088.

References: 1. NUBEQA (darolutamide) [prescribing information]. Whippany, NJ: Bayer HealthCare Pharmaceuticals, Inc.; June 2025. 2. Fizazi K, Shore N, Tammela TL, et al. Nonmetastatic, castration-resistant prostate cancer and survival with darolutamide. N Engl J Med. 2020;383(11):1040-1049. 3. Fizazi K, Shore N, Tammela TL, et al. Darolutamide in nonmetastatic, castration-resistant prostate cancer. N Engl J Med. 2019;380(13):1235-1246.

IN nmCRPC, NUBEQA SIGNIFICANTLY IMPROVED MFS AND OS

NUBEQA helped men live >2x longer without cancer spreading vs ADT alone¹

In nmCRPC, NUBEQA reduced risk of death by >30% vs ADT alone^1,2

NUBEQA + ADT delayed time to pain progression by 14.9 months over ADT alone^1,2

Postpone cytotoxic chemotherapy for more time before starting chemo^1,2