Regulatory Decision Summary for Opdivo

The purpose of this Supplement to a New Drug Submission (SNDS) was to seek market authorization for Opdivo to be used in combination with cisplatin and gemcitabine for the treatment of adult patients with unresectable or metastatic urothelial carcinoma. This submission was filed under the Priority Review Policy.

The submission was classified as a Project Orbis Type B submission and Health Canada collaborated with health authorities from the United States, Australia, Singapore, Switzerland, the United Kingdom, Brazil, and Israel for the review.

After evaluation of the submitted data package, Health Canada authorized Opdivo for the following indication: Opdivo, in combination with cisplatin and gemcitabine, is indicated for the first-line treatment of adult patients with unresectable or metastatic urothelial carcinoma.

The market authorization of Opdivo was based on the results of a pivotal Phase 3, randomized, open-label study in adult patients with unresectable or metastatic urothelial carcinoma, who had not received previous treatment for their metastatic disease. Patients were randomized to receive either Opdivo in combination with cisplatin and gemcitabine or cisplatin and gemcitabine alone.

A statistically significant improvement in overall survival (OS) and progression-free survival (PFS) was demonstrated for patients who received Opdivo plus cisplatin and gemcitabine compared to patients who received cisplatin and gemcitabine alone, with a hazard ratio (HR) (95% confidence interval [CI]) for OS of 0.78 (0.63, 0.96), and for PFS of 0.72 (0.59, 0.88). A higher percentage of patients in the Opdivo plus cisplatin and gemcitabine arm (57.6%) compared to cisplatin and gemcitabine alone (43.1%) achieved an objective response.

The safety profile of Opdivo in combination with cisplatin and gemcitabine is consistent with the known safety profile of Opdivo and the safety profiles of the other components of the treatment regimen. Immune-mediated adverse reactions were observed, consistent with the safety profile of Opdivo. These adverse reactions can be managed in most cases and the Opdivo Product Monograph adequately captures these and other risks of treatment and includes strategies for the management of immune-mediated adverse reactions.

Overall, Opdivo in combination with cisplatin and gemcitabine provides an effective first-line treatment option for adult patients with unresectable or metastatic urothelial carcinoma. When administered at the authorized dosage, the Opdivo-containing regimen is expected to provide a clinical benefit with a manageable safety profile. Risks have been communicated in the approved Product Monograph and will continue to be monitored post market as outlined in the Risk Management Plan, with routine and non-routine pharmacovigilance activities. The benefit/risk profile of Opdivo in combination with cisplatin and gemcitabine is considered favourable for the authorized indication when used under the conditions of use recommended in the approved Product Monograph. Therefore, a Notice of Compliance (NOC) was recommended.

For further details about Opdivo, please refer to the Product Monograph, approved by Health Canada and available through the Drug Product Database.