The FDA granted accelerated approval for Padcev (enfortumab vedotin-ejfv) to treat adults with locally advanced or metastatic urothelial cancer who have previously received a PD-1/L1 inhibitor and a platinum-containing chemotherapy before (neoadjuvant) or after (adjuvant) surgery or in a locally advanced or metastatic setting.

Padcev, an antibody-drug conjugate targeting Nectin-4, comes from Seattle Genetics Inc., of Bothell, Wash., and Tokyo-based Astellas Pharm Inc. Nectin-4 is a protein on the surface of cells and is expressed in bladder cancer. The non-clinical data suggested Padcev would bind to Nectin-4 expressing cells then release monomethyl auristatin E, an anti-tumor agent, into the cell and halting cell reproduction then killing the cell.

While this is the first FDA-approved treatment for those patients, continued approval hangs upon verification and the clinical benefits of confirmatory trials. A global, randomized phase III confirmatory clinical trial is underway. On Dec. 3, Astellas agreed to work with Merck & Co. Inc. to evaluate a combination of enfortumab vedotin and Merck's anti-PD-1 therapy, Keytruda (pembrolizumab), in patients with previously untreated metastatic urothelial cancer.

In this morning’s conference call with investors, Todd Simpson, Seattle Genetics’ chief financial officer, said a course of therapy would be $110,000 to $120,000, based on the treatment duration.

“We must get into the market to see how it unfolds in a commercial setting,” he added.

Simpson projected Medicaid use of about $90,000 per course of therapy.

The approval springs from the EV-201 phase II trial, a single-arm, multicenter study of 125 patients who had previously been treated with a PD-1 or PD-L1 inhibitor and a platinum-based chemotherapy. The primary endpoint of confirmed objective response rate was 44% per blinded independent central review.  Among patients treated with the single agent PADCEV, 12% experienced a complete response and 32% experienced a partial response.

The median tumor response duration, a secondary endpoint, was 7.6 months.

Common serious adverse reactions were urinary tract infection (6%), cellulitis (5%), febrile neutropenia (4%), diarrhea (4%), sepsis (3%), acute kidney injury (3%), dyspnea (3%), and rash (3%).

The most common adverse reaction leading to discontinuation was peripheral neuropathy (6%).

The most common adverse reactions (≥20%) were 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 most common Grade ≥3 adverse reactions (≥5%) were rash (13%), diarrhea (6%) and fatigue (6%).

Bladder cancer is one of the most frequently occurring tumors, with an estimated 699,450 people living with bladder cancer and more than 80,000 new cases diagnosed each year in the U.S.

Seattle Genetics stock (NASDAQ:SGEN) was up 3% shortly after the market opened.

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