FDA Grants Accelerated Approval for Padcev - Keytruda Combo

The FDA granted accelerated approval to Astellas Pharma and Seagen’s combination treatment for locally advanced or metastatic urothelial cancer (la/mUC) who are not eligible to receive cisplatin-containing chemotherapy.

The combination of Padcev (enfortumab vedotin-ejfv) with Merck’s Keytruda (pembrolizumab) has a potentially large market: approximately 8,000 to 9,000 U.S. patients would be eligible for this combination in the U.S., Ahsan Arozullah, M.D., M.P.H., senior vice president, head of Oncology Development at Astellas, told Formulary Watch. It is estimated that approximately 82,290 people in the U.S. will be diagnosed with bladder cancer in 2023, he added.

“Approximately half of the patients with locally advanced/metastatic urothelial cancer (la/mUC) are considered ineligible for first-line cisplatin-based chemotherapy because of low/poor kidney function, poor performance status and/or comorbidities,” Arozullah said. "With this approved combination, this patient population now has an additional treatment option after historically having very few treatment options.

The wholesale acquisition cost (WAC), for Padcev per 30 mg single dose vial is $3,828 and $2,552 per 20 mg single dose vial. A spokesperson told Formulary Watch that list prices do not reflect insurance coverage or what most purchasers and patients actually pay for Padcev, and that the manufacturers cannot yet comment on the WAC for the combined treatment.

While the blockbuster cancer drug Keytruda is a registered trademark of Merck Sharp & Dohme, a subsidiary of Merck, Astellas and Seagen have a clinical collaboration agreement with Merck to evaluate the combination treatment for bladder cancer.

The indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication is contingent upon verification and description of clinical benefit in the EV-302 confirmatory trial, Astellas and Seagen said.

In the EV-103 clinical trial, the use of Padcev in combination with pembrolizumab resulted in confirmed and durable tumor responses in over two-thirds of patients with advanced bladder cancer, said David R. Epstein, CEO of Seagen.

The approval is based on objective response rates (ORR) and median duration of response (DOR) in the phase 1b/2 EV-103 trial (NCT03288545, also known as KEYNOTE-869). In these EV-103 cohorts, patients treated with Padcev in combination with pembrolizumab obtained a 68% confirmed ORR per RECIST v1.1 by blinded independent central review (BICR), with 12% of patients experiencing a complete response and 55% of patients experiencing a partial response.

The median DOR per BICR for Dose Escalation/Cohort A was 22.1 months (range: 1.0+ to 46.3+) and was not reached (range: 1.2 to 24.1+) for Cohort K. The median number of treatment cycles (per 21-day treatment cycle) was nine in Dose Escalation/Cohort A and 11 in Cohort K.

Results from Cohort K were presented in a late-breaking session at the 2022 European Society for Medical Oncology (ESMO) Congress. Additionally, results from Dose Escalation/Cohort A were published in the Journal of Clinical Oncology.

The U.S. Prescribing Information for Padcev includes a BOXED WARNING for Serious Skin Reactions as well as the following Warnings and Precautions: hyperglycemia, pneumonitis/interstitial lung disease, peripheral neuropathy, ocular disorders, infusion site extravasation, and embryo-fetal toxicity.

The combination therapy was granted Breakthrough Therapy designation by the FDA in February 2020 and was granted Priority Review in December 2022.