About NUBEQA® (darolutamide) in nmCRPC

Delay metastasis and improve overall survival

NUBEQA + ADT delivers:

• 40.4 months MFS - more than double the median MFS vs ADT alone
• 31% reduced risk of death vs. placebo+ ADT (secondary endpoint)^*

Maintain your patient’s current lifestyle

NUBEQA + ADT delivers:

• Discontinuation rate comparable to ADT (8.9% vs. 8.7%)
• The only ARI with <1% increase in treatment discontinuation when added to ADT in Phase 3 clinical trial

^* At 3 years, the overall survival with NUBEQA + ADT was 83% (95% CI: 80 to 86) vs 77% (95% CI: 72 to 81) in the placebo group.

^* 73% of all patients had a Gleason score ≥7 at diagnosis.

NUBEQA's efficacy, supported by robust clinical data and extensive real-world evidence, is reflected in recommendations by NICE, acceptance by SMC, and inclusion in international guidelines.

In the Phase 3 ARAMIS trial, NUBEQA added to ADT significantly slowed tumor progression by 22 months and extended overall survival by >30% in patients with high-risk nmCRPC vs. ADT alone.

Adapted from Fizazi et al. 2019.

• NUBEQA + ADT more than doubled the median MFS vs. placebo + ADT (40.4 months vs. 18.4 months, HR: 0.41; 95% CI: 0.34–0.50; p<0.001).

Overall survival in men with nmCRPC (pre-specified final analysis)

NUBEQA + ADT:

31% reduced risk of death

vs. placebo + ADT (secondary endpoint)

^‡

Adapted from Fizazi K et al. 2020.

• NUBEQA + ADT reduced the risk of death by 31% vs. placebo + ADT (secondary endpoint; HR: 0.69; 95% CI: 0.53–0.88; p=0.003; median OS not yet reached for either treatment arm)^‡
• At 3 years, the overall survival with NUBEQA + ADT was 83% (95% CI: 80 to 86) vs 77% (95% CI: 72 to 81) in the placebo group

^‡ ARAMIS trial. Men with high-risk nmCRPC. NUBEQA + ADT (n=955) vs. placebo + ADT (n=554). Primary endpoint was median MFS. Median MFS for NUBEQA + ADT was 40.4 months (n=955) vs. 18.4 months for placebo + ADT (n=554) (HR: 0.41; 95% CI: 0.34–0.50; p<0.001). 31.0% reduction in risk of death vs. ADT alone (HR: 0.69; 95% CI: 0.53–0.88; p=0.003); Number of patients with events 148/955 (15.5%) vs. 106/554 (19.1%) with placebo + ADT. Final analysis for OS was conducted after 254 deaths.

In the Phase 3 ARAMIS trial, the pre-specified final analysis showed that adding NUBEQA to ADT was associated with benefits for all key secondary endpoints and significantly prolonged:

• Time to pain progression
• Time to initiation of first chemotherapy
• Time to first symptomatic skeletal event

NUBEQA + ADT offers 15 months longer without pain progression vs. placebo + ADT

^*

Adapted from Fizazi K et al. 2019.

^* ARAMIS trial. Men with nmCPRC. NUBEQA + ADT (n=955) vs. placebo + ADT (n=554). Primary endpoint was median MFS.

In the Phase 3 ARAMIS trial, there was no increase in discontinuation due to AEs with NUBEQA + ADT vs ADT alone (8.9% vs. 8.7%).

High-risk nmCRPC

^‡

Adapted from Fizazi K et al. 2019.

• Fatigue was the only AE to occur at an incidence of ≥10% with NUBEQA.

^‡ ARAMIS trial. Men with high-risk nmCRPC. NUBEQA + ADT (n=955) vs. placebo + ADT (n=554). Primary endpoint was median MFS.

AEs of concern to people with high-risk nmCRPC were of similar incidence with NUBEQA + ADT and placebo + ADT

^*

Adapted from Fizazi K et al. 2019.

• The most frequently observed adverse reactions in patients receiving NUBEQA were fatigue/asthenic conditions (≥1/10) and rash, pain in the extremity, musculoskeletal pain, fractures, ischaemic heart disease and heart failure (≥1/100)
• With the exception of hypertension and urinary retention, there was very low incidence (<1%) of grade 3 or 4 AEs with NUBEQA + ADT
  • NUBEQA + ADT vs. ADT alone: Hypertension (3.1% vs. 2.2%); urinary retention (1.6% vs. 2.0%)

^* ARAMIS trial. Men with high-risk nmCRPC. NUBEQA + ADT (n=955) vs. placebo + ADT (n=554). Primary endpoint was median MFS.

For the full list of AEs, please refer to the

Summary of Product Characteristics

.

30.1% of patients remained on NUBEQA for ≥4 years

^†

^† ARAMIS Rollover study.

ADT: androgen deprivation therapy; AE: adverse event; AST: aspartate aminotransferase.

Total daily dose 1200 mg. Administered without steroids

Renal impairment

• No dose adjustment is necessary for patients with mild or moderate renal impairment
• For patients with severe renal impairment (eGFR 15–29 mL/min/1.73 m²) not receiving haemodialysis, the recommended starting dose is 300 mg twice daily

Hepatic impairment

• No dose adjustment is necessary for patients with mild hepatic impairment
• Available data on NUBEQA pharmacokinetics in moderate hepatic impairment is limited. NUBEQA has not been studied in patients with severe hepatic impairment. For patients with moderate and severe hepatic impairment (Child-Pugh Classes B and C), a starting dose of 300 mg twice daily is recommended

Elderly

• No dose adjustment is necessary in elderly patients

Paediatric populations

• There is no relevant use of darolutamide in the paediatric population

Missed doses

• If a dose is missed, the dose should be taken as soon as the patient remembers prior to the next scheduled dose
• The patient should not take two doses together to make up for a missed dose

For more information about dosing modifications, missed doses, special warnings, precautions and interactions, please refer to the Summary of Product Characteristics.