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IMPORTANT SAFETY INFORMATION

Embryo-Fetal Toxicity: Safety and efficacy of NUBEQA have not been established in females. NUBEQA can cause fetal harm...  Continue reading »

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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. Continue reading »

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PRECLINICAL STUDIES OF BLOOD-BRAIN PENETRATION AND MOA

 

ARAMIS IS THE LARGEST PHASE III STUDY IN nmCRPC TO DATE1-3

 

 

    Study design: double-blind, placebo-controlled, international, multicenter study, non-metastatic CRPC (N=1509)
    • Treatment continued until radiographic disease progression as assessed by conventional imaging (CT, MRI, 99mTc bone scan) by blinded independent central review, discontinuation due to adverse reactions, or withdrawal of consent

    *All patients received concurrent ADT (treatment with GnRH analog or previous bilateral orchiectomy).

    Lymph nodes located below the aortic bifurcation as measured by the short axis.

    CRPC=castration-resistant prostate cancer; PSADT=PSA doubling time; PSA=prostate-specific antigen; ECOG PS=Eastern Cooperative Oncology Group performance status; CT=computed tomography; MRI=magnetic resonance imaging; GnRH=gonadotropin-releasing hormone;

    Study arms in ARAMIS study: Baseline characteristics, NUBEQA (darolutamide) + ADT (n=955), ADT Alone (n=554)
    • ECOG performance status is graded according to the following criteria: 0: Fully active, able to carry on all pre-disease performance without restriction; 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature, eg, light housework, office work5
    • Bone-sparing agents included bisphosphonates, denosumab, vitamin D and analogs, calcium and calcium combinations, fluorides, and calcitonins6
    • Common previous hormonal therapies for prostate cancer (received by ≥10% of all patients) included leuprolide (52%), goserelin (32%), triptorelin (29%), bicalutamide (66%), flutamide (13%), and cyproterone (11%)4

    DELAY METASTASIS, HELP PATIENTS LIVE LONGER WITHOUT PROGRESSION

     

    Significant increase in MFS vs ADT alone1,4

    • MFS results were consistent across patient subgroups for1:
      • PSA doubling time (≤6 months or >6 months)
      • Prior use of bone-targeting agents (yes or no)

    *95% CI: 34.3-NE. 95% CI: 15.5-22.3.

    MFS=metastasis-free survival; ADT=androgen-deprivation therapy; PSA=prostate-specific antigen; HR=hazard ratio; CI=confidence interval; NE=not estimable.

    Extend overall survival, so patients have more time to live7

    • OS was statistically significant despite3:
      • 31% (n=170) of patients in the ADT arm who crossed over to NUBEQA
      • 55% (n=307) of patients in the ADT arm who crossed over to NUBEQA or received another life-prolonging therapy prior to this analysis
    • With more than half of patients still alive at the final analysis, median OS was not reached. Median not estimable for both arms3

    Statistically significant delay in time to pain progression1,3

    • NUBEQA + ADT delayed median time to pain progression by nearly 59% vs ADT alone1
    • Time to pain progression was defined as at least a 2-point worsening from baseline of pain score on Brief Pain Inventory Short Form (a validated health-related quality-of-life instrument) or initiation of opioids and reported in 28% of all patients on study1

    More time without cytotoxic chemotherapy1,3

    Prespecified secondary endpoints in overall survival, time to pain progression, and time to cytotoxic chemotherapy: Median Duration (mo), NUBEQA (darolutamide) + ADT (955), ADT alone (554), HR (95% CI)

    *95% CI: 0.80-0.86. 95% CI: 0.69-0.80.
    Median: NE for both NUBEQA + ADT (n=955) and ADT alone (n=554).

    • NUBEQA + ADT delayed median time to pain progression by nearly 59% vs ADT alone1
    • Time to pain progression was defined as at least a 2-point worsening from baseline of pain score on Brief Pain Inventory Short Form (a validated health-related quality-of-life instrument) or initiation of opioids and reported in 28% of all patients on study1

    Adding NUBEQA kept PSA lower for longer

    • PSA dropped by an average of >90% from baseline on NUBEQA1

     

      Prespecified secondary endpoints in overall survival, time to pain progression, and time to cytotoxic chemotherapy: Median Duration (mo), NUBEQA (darolutamide) + ADT (955), ADT alone (554), HR (95% CI)

      Median: NE for both arms.
      §Median: 40.3 mo, NUBEQA + ADT: 25.4 mo, ADT alone.

      IMPORTANT SAFETY INFORMATION (cont’d)

      Adverse Reactions (cont'd)
      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).

      Please see additional Important Safety Information below.

      SAME LOW RATE OF PERMANENT DISCONTINUATION

       

      PRESCRIBE NUBEQA with confidence

      Same low rate of permanent discontinuation due to adverse reactions vs ADT alone1

      The most frequent reasons in patients treated with NUBEQA included cardiac failure (0.4%) and death (0.4%)

      Low rates of dose reductions and interruptions due to adverse reactions1

      Three adverse reactions occurred more frequently with NUBEQA + ADT (≥2% over ADT alone)1

      • Overall, serious adverse reactions occurred in 25% of men receiving NUBEQA + ADT and in 20% of men receiving ADT alone1
        • Serious adverse reactions in ≥1% of men who received NUBEQA + ADT included urinary retention, pneumonia, and hematuria
      • Additionally, clinically significant adverse reactions occurring in ≥2% of men treated with NUBEQA + ADT vs ADT alone included ischemic heart disease (4.0% vs 3.4%) and heart failure (2.1% vs 0.9%)1
      Low incidence of grade 3-4 fatigue, pain in extremity, and rash1

      Other AEs examined in the first and final analyses of ARAMIS4,6,7


      Click each category below to view the first analysis AEs compared to the final analysis AEs.

        Other adverse events examined in ARAMIS study, % all grades, % grades 3/4
         
         
         
         
        • No cardiovascular AEs in either arm increased >2% between first and final analysis
        • AEs were generally consistent from first to final analysis1-3
          • No AE in either arm increased by >2%
          • Final analysis conducted at 14 months after first analysis
        Central nervous system adverse events examined in ARAMIS study, % all grades, % grades 3-4
         
         
         
         
         
         
         
         
         
         
         
         
        • No CNS AEs occurred ≥2% over ADT alone
        • AEs were generally consistent from first to final analysis
          • No AE in either arm increased by >2%
          • Final analysis conducted at 14 months after first analysis
        Gastrointestinal and genitourinary adverse events examined in ARAMIS study, % all grades, % grades 3-4
         
         
         
         
        • No cardiovascular AEs in either arm increased >2% between first and final analysis
        • Consistent safety profile from first to final analysis
          • No AE in either arm increased by >2% (14-month follow-up)
        Metabolic adverse events examined in ARAMIS study, % all grades, % grades 3-4
         
         
        • No cardiovascular AEs in either arm increased >2% between first and final analysis
        • Consistent safety profile from first to final analysis
          • No AE in either arm increased by >2% (14-month follow-up)
        Musculoskeletal adverse events examined in ARAMIS study, % all grades, % grades 3-4
        • No cardiovascular AEs in either arm increased >2% between first and final analysis
        • Consistent safety profile from first to final analysis
          • No AE in either arm increased by >2% (14-month follow-up)
        Other adverse events examined in ARAMIS study, % all grades, % grades 3-4
        • No cardiovascular AEs in either arm increased >2% between first and final analysis
        • Consistent safety profile from first to final analysis
          • No AE in either arm increased by >2% (14-month follow-up)