Regulatory Decision Summary for Zytiga
The Regulatory Decision Summary explains Health Canada’s decision for the product seeking market authorization. The Regulatory Decision Summary includes the purpose of the submission and the reason for the decision.
Type of submission:
What was the purpose of this submission?
This Supplement to a New Drug Submission was filed to receive market authorization for the use of Zytiga in combination with prednisone and androgen depletion therapy (ADT) for the treatment of patients with newly diagnosed high-risk metastatic prostate cancer, who may have received up to 3 months of prior ADT.
Why was the decision issued?
The purpose of this submission was to receive market authorization for the use of Zytiga in combination with prednisone and androgen depletion therapy (ADT) for the treatment of patients with newly diagnosed high-risk metastatic prostate cancer, who may have received up to 3 months of prior ADT.
Study 3011 was a randomized, double-blind, placebo-controlled study which compared ADT plus abiraterone acetate (1,000 mg daily) plus low dose prednisone (5 mg once daily) versus ADT alone in patients with newly diagnosed (within 3 months prior to randomization) prostate cancer with high-risk prognostic factors. The addition of abiraterone acetate plus prednisone to ADT resulted in a statistically significant improvement in overall survival (OS) [Hazard Ratio (HR) = 0.621; 95% CI: 0.509, 0.756; p<0.0001] and radiographic progression-free survival (rPFS) (median rPFS 33 months vs 14.8 months HR = 0.466; 95% CI: 0.394, 0.550; p<0.0001) in the treatment group vs the placebo group. A statistically significant advantage for all secondary endpoints (time to Skeletal Related Events, time to subsequent therapy for prostate cancer, time to initiation of chemotherapy, time to pain progression, and time to PSA progression) was also achieved for the treatment group.
The most frequently reported adverse events in Study 3011 were hypertension, hypokalemia and back pain. The known adverse events associated with the use of abiraterone acetate, in addition to the ones listed above, include fluid retention/edema, cardiac disorders (mostly arrhythmias, ischemic heart disease and cardiac failure), liver toxicity, cataract, osteoporosis-related fractures, rhabdomyolysis, allergic alveolitis. Other important information includes drug-drug interactions (abiroterone is an inhibitor of hepatic enzyme CYP2D6, caution is advised when Zytiga is administered with drugs metabolized by CYP2D6, particularly with drugs that have a narrow therapeutic index) and food effect (abiraterone Cmax and AUC were approximately 7- and 5-fold higher when taken with food; this drug must be taken on an empty stomach). Clinically important adverse events include diarrhea, sexual dysfunction, thrombocytopenia, dyspepsia, urinary tract infection, and hematuria.
No new safety concerns have been identified in the current submission. However, the incidence of hypertension and hypokalemia was higher in the hormone-sensitive prostate cancer population of Study 3011, when compared with the previous Phase III studies in the metastatic castration-resistant prostate cancer population. The sponsor has provided information on the management of persistent hypokalemia in the product monograph.
The benefit risk-profile of Zytiga when used for the approved indication is considered positive.
Approved; issued a Notice of Compliance in accordance with the Food and Drug Regulations.