Regulatory Decision Summary for Cysview

This Supplemental New Drug Submission (SNDS) was filed for Cysview for a revision of the currently approved indication to “as an adjunct to white-light cystoscopy in the management of non-muscle invasive bladder cancer, including carcinoma in situ (CIS), in patients with known or suspected bladder cancer to increase tumor detection and reduce recurrence risk.” Upon review of the submitted data package, Health Canada authorized the following modification to the indication “as an adjunct to white-light cystoscopy in the diagnosis and follow-up of non-muscle invasive bladder cancer, including carcinoma in situ (CIS), in patients with known or suspected bladder cancer to increase tumor detection”.

The proposed modifications to the indication were supported by one pivotal study, which was a prospective, open label, comparative, within-patient controlled, multicenter, phase 3 study of blue light cystoscopy (BLC) with Cysview and white light cystoscopy (WLC). The objectives of the study were (i) to compare BLC with Cysview to WLC in the detection of bladder cancer in surveillance setting, (ii) to assess the efficacy and safety of BLC with Cysview after repetitive use, and (iii) to compare BLC with Cysview to WLC in the detection of carcinoma in situ (CIS). Adult patients with non-muscle invasive bladder cancer with high risk of tumor recurrence scheduled for follow-up for tumor recurrence were included in the study. The overall mean age of patients enrolled in the study was 68.9 years (± 10.4), and 79.7% were male. The majority of the study population (89.5%) was White.

The primary efficacy endpoint was the proportion of patients with histologically confirmed malignancy that was detected only by BLC with Cysview and not by WLC in the surveillance setting. A total of 310 patients were enrolled. Of these, 304 patients received a Cysview instillation in the surveillance setting with WLC and BLC. Suspected lesions using either method were counted. One-hundred three (103) patients had lesions suspected of bladder cancer recurrence in the surveillance setting. These patients proceeded to receive BLC with Cysview and WLC in the operating room setting within 6 weeks. Suspicious lesions were biopsied to confirm malignancy and surgically removed by transurethral resection of the bladder. Pathological evaluation was performed by a centralized blinded panel.

The efficacy of Cysview BLC in the surveillance setting was demonstrated: the proportion of patients with histologically confirmed malignancy, including CIS, detected only by BLC with Cysview exceeded that detected by WLC. Of 103 patients, 63 had at least one confirmed malignant lesion, including 13 (20.6%, p<0.0001) patients with malignancy detected only by BLC with Cysview, 1 (1.6%) patient who had malignancy detected only with WLC, and 49 (77.8%) patients with malignancy detected by both BLC with Cysview and WLC. The efficacy of Cysview BLC in the detection of CIS was evaluated in this study as the proportion of patients with one or more CIS lesions detected with Cysview BLC and none with WLC. Of the 63 patients with confirmed lesions, 26 patients had at least one CIS lesion, including 9 (34.6%, p<0.0001) patients who had at least one of the CIS lesions detected only by BLC with Cysview and none by WLC. Two patients had at least one CIS lesion detected only by WLC and none by BLC with Cysview, and 15 patients had CIS-lesions detected by both BLC with Cysview and WLC. Of the 103 evaluable patients, 20 had false positive lesions seen only with BLC with Cysview (19.4%; 95% CI: 12.3% to 28.4%). In comparison, three patients had false positive lesions seen only with WLC (2.9%; 95% CI: 0.6% to 8.3%). Seventeen patients (16.5%) had false positive lesions seen with both BLC with Cysview and WLC.

The main goal of the safety review was to assess the safety of Cysview after repeated administration. A single event of contact dermatitis occurred after repeat administration of Cysview. The safety of blue light was not specifically evaluated in the study, thus, the uncertainty of its safety still remains as is stated in the approved Product Monograph. No additional safety concerns were identified during the review.

An updated Risk Management Plan for Cysview was reviewed by Health Canada and considered acceptable. The final labelling and Product Monograph were considered acceptable.

The proposed indication was modified based on the review of the safety and efficacy data. Overall, the benefit-harm-uncertainty profile was favourable for Cysview for the approved 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 Cysview, please refer to the PM, approved by Health Canada and available through the Drug Product Database.