The FDA is drawing a hard line on drug approvals, questioning whether single-arm trial data is enough to back a new bladder cancer treatment. As pressure mounts to approve faster, the agency fears lowering the bar could set a risky precedent for future cancer therapies.
The case in point, whether a new bladder cancer treatment, UGN-102 by UroGen Pharma, has what it takes to earn approval, without the usual gold-standard randomized controlled trial. The sponsor has submitted a market approval application using data from a single-arm study to prove the treatment’s safety and effectiveness for patients with recurrent, low-grade, intermediate-risk non–muscle invasive bladder cancer (NMIBC).
UGN-102 is a drug formulation of mitomycin designed to be administered directly into the bladder via a simple in-office procedure. It’s being pitched as a more patient-friendly option compared to transurethral resection of bladder tumor (TURBT), the current standard, which is a surgical intervention typically performed under general anesthesia. In UroGen’s Phase 3 ENVISION trial, 223 patients received six weekly instillations. The results looked promising on the surface: nearly 78% of participants saw complete disappearance of tumors by three months. At the one-year mark, about 80% of those responders were still cancer-free; at 18 months, just over half had maintained remission.
UroGen emphasized that their treatment could potentially reduce the number of repetitive TURBT surgeries, especially valuable for elderly patients with other health conditions. The therapy’s convenience and less invasive nature were highlighted as major advantages. However, these benefits come with a caveat: there was no control group in the ENVISION trial. That leaves the FDA and its advisory committee struggling to interpret the data. Was the success of UGN-102 due to the drug, or would many of these patients have remained recurrence-free anyway?
The FDA has expressed skepticism, noting that without a comparator arm, it’s impossible to truly assess how UGN-102 stacks up against TURBT in either safety or efficacy. The agency pointed out that even though side effects were generally mild and genitourinary in nature, they lasted over six weeks, compared to the shorter side effect window after a single TURBT procedure. The FDA also noted that UroGen failed to demonstrate that the new treatment is safer or more tolerable than the existing standard.
UroGen had started a randomized trial but terminated it early due to disagreements with the FDA about trial design. This only fueled more concern. During the advisory meeting, the FDA didn’t ask the committee to recommend approval. Instead, it asked a more focused question: Is the overall benefit-risk balance of UGN-102 favorable based on the current data?
The panel was split—five said no, four said yes. Those voting against it cited the absence of a comparator and the high cost of the drug (estimated at $140,000) without a clear demonstration of better outcomes. They emphasized that a randomized trial would have provided much-needed clarity. On the other hand, those in favor saw the long-lasting response rates and manageable side effects as strong indicators of potential, especially given the appeal of a non-surgical option for older patients.
Ultimately, the FDA now faces a tough call: move forward with an approval based on limited evidence and risk setting a precedent, or hold the line and demand more robust data. Committee members generally agreed that randomized trials should be required for future similar treatments, provided they don’t stall access to promising innovations.
