Merck, Astellas and Pfizer bring down the house with Keytruda-Padcev FDA nod in bladder cancer

The combination therapy was hailed with a standing ovation in October at the European Society for Medical Oncology (ESMO) conference in Madrid. Less than two months later, the FDA has added its acclaim—blessing it five months ahead of its PDUFA date.

On Friday the U.S. regulator signed off on Astellas and Pfizer’s Padcev in combination with Merck’s Keytruda as a first-line treatment for bladder cancer. The full endorsement, which follows an accelerated nod eight months ago, puts the combo on course to replace chemotherapy as the standard of care in locally advanced or metastatic urothelial cancer (la/mUC).

The bravos are for a treatment that reduced the risk of death by 53% compared to chemotherapy in patients with previously untreated bladder cancer. The full green light doubles the eligible patient population, as the accelerated nod was limited to patients who could not receive chemo.

The FDA decision came one day after Pfizer completed its $43 billion buyout of Seagen, which developed the antibody-drug conjugate (ADC) Padcev.

The combination is the first regimen approved for advanced bladder cancer that has shown superiority to platinum chemotherapy, the “gold standard for decades,” Astellas’ oncology development chief, Ahsan Arozullah, M.D., noted in a release.

In the EV-302 phase 3 study of 886 untreated patients, the combo produced a median overall survival (OS) rate of 31.5 months compared to 16.1 months for chemo. The combo produced similar success in progression-free survival (PFS), reducing the risk of disease progression or death by 55%. Patients on the combo regimen lived a median of 12.5 months without progression, versus 6.3 months for the chemo arm.

Two months ago in an interview, when he was Seagen’s R&D chief, Roger Dansey called the results “practice-changing." Dansey now serves as Pfizer's chief development officer for oncology,

“It’s rare that a trial comes along and really does offer that transformative element,” Dansey said. “The initial data with Padcev and Keytruda was really eye-opening because it started to hint at the potential value of combining an ADC, using Seagen’s technology, together with a PD-1 inhibitor, such that you get the benefits of a highly active direct therapy, the ADC, together with immunotherapy intervention.”

As Padcev and Keytruda take on added use in the indication, it will be important to measure the effectiveness of the combo in subgroups, analysts at Leerink Partners wrote in September.

The companies also are investigating Padcev as a solo agent and in combination with Keytruda as first- and second-line treatments for patients with la/mUC with muscle-invasive bladder cancer (MIBC). They also are studying Padcev-Keytruda in previously untreated recurrent/metastatic head and neck squamous cell carcinoma.