Common Form of Bladder Cancer: FDA Finalizes Guidance

Regulatory NewsRegulatory News | 12 February 2018 |  By 

The US Food and Drug Administration (FDA) on Monday finalized guidance providing recommendations to drugmakers for developing new drugs and biologics to treat bacillus Calmette-Guérin (BCG)-unresponsive nonmuscle invasive bladder cancer (NMIBC), the most prevalent form of bladder cancer in the US.

Intravesical immunotherapy with live attenuated BCG remains the standard of care for patients with bladder cancer. However, to date FDA has approved just one other therapy for NMIBC, Valstar (valrubicin), which the Bladder Cancer Advocacy Network (BCAN) says has a "very limited indication and has limited efficacy."

The supply of BCG has also been constrained in recent years as Sanofi Aventis, one of two companies that recently manufactured BCG stopped production of the therapy in 2016, leaving NMIBC patients with limited treatment options.

In terms of changes between the draft and final guidance, FDA said: "In addition to editorial changes made primarily for clarification, noteworthy substantive changes are as follows: clarification of the definition of BCG-unresponsive disease and detailed information concerning the definition of complete response."


The guidance finalizes a draft version released in November 2016 and follows discussions held at the FDA/American Urological Association Bladder Cancer Workshop in May 2013.

While FDA says the recommendations made in the guidance can apply to drugs intended to treat BCG-unresponsive NMIBC and other forms of NMIBC, its recommendations may not apply in all cases and FDA says that sponsors should discuss their specific development plans with the agency.

For drugmakers looking to develop products to treat BCG-unresponsive NMIBC, FDA says the clinical endpoint chosen should depend on whether patients in the study have active disease at the time of enrollment.

"For patients without active disease (disease was reseected at or before trial entry), FDA recommends a randomized, controlled trial design using a time-to-event endpoint such as recurrence-free survival. In contract, patients with carcinoma in situ (CIS) at trial entry can be studied in either a randomized, controlled trial or a single-arm trial," FDA writes.

FDA notes that in BCG-unresponsive NMIBC, a single-arm study measuring complete response rate and duration of response can be sufficient to demonstrate effectiveness.

For sponsors looking to develop systemic therapies for BCG-unresponsive NMIBC, FDA says that early stage trials should be limited to patients with few other treatment options due to heightened safety concerns with systemic drugs.

FDA, Federal Register Notice


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