Flexible Scope Indication Approved for Bladder Imaging Agent

Ashish Kamat, MD

The FDA recently approved a supplemental new drug application (sNDA) for Blue Light Cystoscopy (BLC) with Cysview for surveillance of bladder cancer, according to Photocure, the manufacturer of Cysview.¹

Photocure sought to expand the label to include use in the outpatient setting to detect the recurrence of bladder cancer using a flexible cystoscope and received a priority review for the sNDA in October 2017. The agent was previously approved for use only in rigid cystoscopy. Additionally, the sNDA included a request for repetitive use of Cysview, which was also approved.

Cysview was initially approved in the United States in 2010 and is currently indicated for use for detection of nonmuscle-invasive bladder cancer (NMIBC) for patients who, based on prior cystoscopy results, have or are suspected to have lesions.² The use of rigid cystoscopes, as an adjunct to white light cystoscopy (WLC), has become a standard of care in the operating room, with proven ability to improve detection and management of NMIBC compared with WLC alone.³

Following instillation of Cysview into the bladder, it crosses the cellular membrane of cancer cells. When examined with a blue light cystoscope the tumors glow bright pink, making it easier for physicians to see them. Patients’ bladders are examined first under standard white light and then a blue light cystoscopic device, according to Ashish Kamat, MD, urologic oncologist, professor of cancer research, director of the Urologic Oncology Fellowship at the University of Texas MD Anderson Cancer Center and one of the investigators for the study used in the sNDA filing.

The sNDA filing was a drug-device application that also seeks an indication for the Karl Storz D-Light C Photodynamic Diagnostic (PDD) Flexible Cystoscopy system in combination with Cysview.¹

The use of Cysview only with a rigid cystoscope requires the patient to be anesthetized and carries additional disadvantages. Cystoscopies are “obviously a lot more painful because it’s a rigid scope, so it’s not something commonly used for surveillance in the office setting,” said Kamat in an interview with OncLive.

The approval of the sNDA was based on positive data from a phase III study that tested Cysview with the flexible scope system. Investigators found that 20.6% of cases of bladder cancer recurrence would have been missed had Cysview not been used (P <.0001). Notably, the study showed that 9 out of 26 flat, more aggressive, high-grade lesions were diagnosed using confirmatory BLC with Cysview, and not with white light. The study also demonstrated that there was no increase in adverse events after repeated administration of Cysview.⁴

“The study design was essentially to see if BLC with Cysview could be used in an office setting, with a flexible cystoscope and if there is an incremental clinical benefit in the detection of tumors. The study was positive for all 3 endpoints,” Kamat commented. The new indications will facilitate detection of recurrence, which is an essential step in managing bladder cancer. One benefit of a flexible, outpatient cystoscopy is that patients can go home soon afterward and experience less pain and discomfort. The other advantage is that when using a flexible cystoscope and having the patient remain conscious, physicians can show the patient what is happening on a screen, better educating them about their disease recurrence, or lack thereof.

Using a flexible scope in the outpatient setting could also reduce the costs of treating and monitoring patients with bladder cancer by treating some smaller lesions in the office. “In patients who present with bladder cancer, one of the biggest problems we have in the United States and globally is that it is one of the biggest health expenditures, both for the patient and for the clinician. It is the most expensive cancer to diagnose and treat, mainly because patients who are fortunate enough to save their bladders have recurrences of tumors, so they have to go through multiple procedures and treatments,” Kamat said.

References

1. Photocure announces U.S. FDA approval of new indication for blue light cystoscopy with Cysview [press release]. Oslo, Norway: Photocure Inc; February 16, 2018. https://globenewswire.com/news-release/2018/02/16/1357299/0/en/Photocure-Announces-U-S-FDA-Approval-of-New-Indications-for-Blue-Light-Cystoscopy-with-Cysview.html. Accessed February 26, 2018.
2. Cysview (hexaminolevulinate hydrochloride) [prescribing information]. Oslo, Norway: Photocure Inc; 2010. https://www.accessdata.fda.gov/drugsatfda_docs/label/2010/022555s000lbl.pdf. Accessed January 5, 2018.
3. Jocham D, Witjes F, Wagner S, et al. Improved detection and treatment of bladder cancer using hexaminolevulinate imaging: a prospective, phase III multicenter study. J Urol. 2005;174(3):862-866. doi: 10.1097/01.ju.0000169257.19841.2a.
4. Positive data from phase 3 US blue light cystoscopy with Cysview study presented at AUA 2017 meeting in Boston [press release]. Princeton, NJ: Photocure Inc; May 14, 2017. https://www.prnewswire.com/news-releases/positive-data-from-phase-3-us-blue-light-cystoscopy-with-cysview-study-presented-at-aua-2017-meeting-in-boston-300457204.html. Accessed January 5, 2018.