Regulatory Decision Summary for OPDIVO

Opdivo is a fully human monoclonal immunoglobulin G4 (IgG4) antibody that is a highly specific programmed death-1 (PD-1) immune checkpoint inhibitor that blocks the interaction between the PD-1 receptor and its ligands PD-L1 and PD-L2. Opdivo was first authorized in Canada for use in the treatment of a melanoma subpopulation (BRAF V600 wild-type).

The market authorization was based on the pivotal study, CA20902, which stopped enrolling subjects at the pre-determined interim analysis for drug efficacy since the drug safety monitoring committee decided to stop enrolling subjects into the study. The study had demonstrated both a statistically and clinically meaningful improvement in overall survival for nivolumab (median survival 25 months compared to 19.5 months in everolimus arm). In addition, there was a statistically and clinically meaningful difference in the overall objective response rate (odds-ratio 5.98).

No drug-related deaths were reported in either the pivotal trial or the supportive clinical trial. No unexpected or new drug-related adverse events were reported in either trial. Furthermore, in the pivotal trial, the safety data demonstrate that the nivolumab safety profile is favorable compared to everolimus, a standard-of-care therapy for patients with advanced renal cell carcinoma, who have received prior systemic therapy. The immune related adverse events (endocrine related disorders, diarrhea/colitis, hepatitis, renal disease, skin rash) and hypersensitivity/ infusion reactions that occurred in persons taking nivolumab were rare and resolved with appropriate management. Nivolumab immunogenicity was reported, but did not appear to be clinically meaningful, based on the lack of reported associated adverse events, including hypersensitivity.

Based on the information submitted for review, the benefit/risk ratio for the use of Opdivo in the treatment of persons with advanced RCC who had received prior systemic therapy was considered to be favourable.