A new untitled letter sent by the US Food and Drug Administration's (FDA) Office of Prescription Drug Promotion (OPDP) claims that a brochure for Photocure ASA's bladder cancer detection solution Cysview omits and minimizes risk information and makes unsubstantiated superiority claims, rendering the product misbranded under federal law.
The drug, Cysview (hexaminolevulinate hydrochloride) for Intravesical Solution, is FDA-approved for the detection of non-muscle invasive papillary cancer of the bladder among patients suspected or known to have lesions.
The drug is used in conjunction with the Karl Storz D-Light C Photodynamic Diangostic (PDD) system to perform cystoscopy using the device's blue light setting.
It is also subject to a number of warnings and contra-indications. For example, it should not be used in repetition due to potential risks associated with repeated exposure, and should not be used in patients with porphyria, gross hematuria, BCG immunotherapy or intravesical chemotherapy within the past 90 days, or known hypersensitivity to hexaminolevulinate or aminolevulinate derivatives.
One of the company's brochures for Cysview, however, omitted some of these contraindications, FDA observed.
The problem has to do with the way one of the warnings is structured. The brochure says that "safety and effectiveness have not been established" in certain patients, when in fact FDA's approved labeling states that safety has been tested, and that the product should explicitly not be used with those patients.
Safety and Efficacy Claims in Question
In other instances, the company neglects to mention certain risks associated with the product's use in approved patients, FDA wrote. For example, the company touts how its product is more effective under blue light than other products, resulting in easier detection of malignant cells. Left unsaid, however, is that the same blue light in combination with Cysview can cause false detections, particularly when in the presence of inflamed tissue, scar tissue or biopsy tissue from previous examinations.
In another example cited by regulators, the company said that patients receiving its product were prone to certain adverse events, including anaphylactic shock. FDA took issue with the company's wording, however, as it was presented "only as a postmarketing adverse event that may be unrelated to the drug." This downplays the risk of the adverse event, FDA argued. Other risks were presented as being uncommon when they were in fact among the drug's most common, FDA added.
In yet another instance, the company described the symptoms of hematuria-blood present in the urine-in terms of the urine having a "pinkish tinge," thereby presenting the risks in a way that consumers might not understand, FDA explained. "Characterizing the risk of hematuria as 'pinkish tinge to the urine,' as opposed to informing patients that they may see blood in their urine, misleadingly suggests that the drug is safer than has been demonstrated," the letter explains.
On the efficacy side of the equation, FDA's letter also takes issue with the company's statement that blue light cystoscopy is more effective than white light cystoscopy. This isn't the case, FDA said. White light is effective at detecting the vast majority of cancerous cells, while blue light is best as an adjunct-not a replacement, regulators said.
In its 4 March 2013 letter, OPDP requests that Photocure make changes to the brochure to bring it into compliance, and to cease its dissemination in the meantime.
Regulatory Focus has reached out to Photocure for a response and will update this story if we hear from them.
Update: In a response to Regulatory Focus, Ambaw Bellete, President and Head of US Cancer Commercial Operations confirmed to Focus that Photocure was in receipt of FDA's letter and is "in the process of finalizing" its response to FDA regarding its allegations.
"We intend to dialog with the FDA and fully comply with their regulations," he added.