FDA Approves Padcev to Treat Bladder Cancer

The Food and Drug Administration (FDA) granted accelerated approval to Padcev (enfortumab vedotin-ejfv) for the treatment of adult patients with locally advanced or metastatic urothelial cancer who have received prior treatment with a PD-1/PD-L1 inhibitor and platinum-containing chemotherapy — the first drug approved for this patient population.

“Metastatic urothelial cancer is an aggressive and devastating disease with limited treatment options, and the approval of Padcev is a significant advance for these patients who previously had limited options after initial therapies failed,” Dr. Jonathan E. Rosenberg, medical oncologist and chief of genitourinary medical oncology service at Memorial Sloan Kettering Cancer Center in New York, said in a press release.

The agency based its decision on data from the multicenter, single-arm, phase 2 pivotal EV-201 trial — designed to evaluate Padcev, which is directed against Nectin-4, a protein located on the surface of cells and highly expressed in bladder cancer, in 125 patients with locally advanced or metastatic urothelial cancer who received prior treatment with a PD-1 or PD-L1 inhibitor and a platinum-based chemotherapy.

“The Padcev clinical trial enrolled a range of patients whose cancer was difficult to treat, including those whose disease had spread to the liver,” Rosenberg added.

Patients demonstrated an objective response rate, the study’s primary endpoint, of 44%, including 15 complete responses (12%) and 40 partial responses (32%). Duration of response, a secondary endpoint, was 7.6 months.

The most common serious side effects were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%) and rash (3%). Peripheral neuropathy led to treatment discontinuation in 6% of patients. Common side effects of any grade included fatigue (56%), peripheral neuropathy (56%), decreased appetite (52%), rash (52%), alopecia (50%), nausea (45%), dysgeusia (42%), diarrhea (42%), dry eye (40%), pruritus (26%) and dry skin (26%).

The first-in-class antibody-drug conjugate is approved under the FDA’s Accelerated Approval Program, which allows approval of a medicine based on a surrogate endpoint if the medicine fills an unmet medical need for a serious condition. In this instance, the accelerated approval was based on tumor response rate.

Continued approval will be contingent upon further evaluation to verify and describe the clinical benefit of the drug in a confirmatory trial.

“The FDA approval of PADCEV is welcome news for patients with bladder cancer,” Andrea Maddox-Smith, chief executive officer of the Bladder Cancer Advocacy Network, said in the release. “Though new medicines for bladder cancer have been approved in recent years, most people living with advanced stages of this disease face a difficult journey with few treatment options.”