A mere 26 months after the first patient was enrolled in its pivotal phase II study and about three months ahead of its PDUFA date, 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.

Seattle Genetics Inc. estimates that about 2,000 to 4,000 patients a year will be diagnosed with the cancer Padcev is designed to treat, though Clay Siegall, Seattle Genetics’ co-founder, chairman, president and CEO, on Thursday likened gauging the exact patient population numbers to “sculpting fog.”

Padcev, an antibody-drug conjugate targeting Nectin-4, comes from Seattle Genetics, 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 nonclinical data suggested Padcev would bind to Nectin-4 expressing cells then release monomethyl auristatin E, an antitumor agent, into the cell and halting cell reproduction then killing the cell.

Clay Siegall, president, CEO, board chairman, Seattle Genetics

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, whose primary endpoint is overall survival, 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 Thursday morning’s conference call with investors, Todd Simpson, Seattle Genetics’ chief financial officer, said a course of therapy would cost between $110,000 and $120,000, based on the treatment duration. On Thursday, J.P. Morgan analyst Cory Kasimov estimated average patient treatment duration at four months, compared to the 4.6 months seen in the clinical trial that led to the approval.

“And obviously, we're going to need to get into the marketplace and understand how this actually unfolds in the commercial setting,” he added.

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

Siegall said the companies took “a hard look” at the price tag.

“But it's really important for us to look at pricing and do studies and look at all of the other oncology drugs and look at the real value that Padcev provided in clinical trials, and come up what we thought was an appropriate price for the company and for patients and for use by doctors, and we feel this is the right price,” he said during Thursday’s investor call. “It's a strong price, but based on the clinical value we saw was we thought very appropriate.”

Padcev is Seattle Genetics’ second marketed product and expands its portfolio into solid tumors.

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. Urothelial cancer, which can also be found in the renal pelvis, ureter and urethra, accounts for 90% of all bladder cancers. Its five-year survival rate is in the single digits, Siegall noted. About 20,000 people in the U.S. present annually with metastatic urothelial cancer.

“Our approval is in a subset of this population who have previously been treated with both a PD-1 or PD-L1 therapy and a platinum regimen,” Roger Dansey, Seattle Genetics’ chief medical officer, said during Thursday’s investor call. “Our next goal is to move Padcev into first-line metastatic urothelial cancer.”

Seattle Genetics stock (NASDAQ:SGEN) closed up 1.86% on Thursday.

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