Drug gets FDA approval plus expansion

Treating Bladder Cancer

There are 573,000 cases of bladder cancer worldwide every year, with more than 212,000 deaths. Patients who did not benefit from conventional chemotherapy have faced a poor outcome.

American pharmaceutical company Seagan, based in Seattle, Washington,  and its Japanese partner Astellas have jointly produced a new bladder cancer drug, Padcev, which has been approved b the Food and Drug Administration (FDA). Moreover, the FDA has also approved Padcev for a second therapeutic use, as a treatment for local advanced or metastatic urothelial cancer.

The approval was based on results from a Phase 3 EV-301 trial, which examined survival rates for patients treated with Padcev against those treated with chemotherapy. Padcev had already been granted “conditional accelerated approval” two years earlier, because it is the only drug available to bladder cancer patients who had not responded to chemotherapy and had no other options. The FDA’s RTOR program (Real Time Oncology Review) exists to speed up approval of cancer drugs for which no alternatives exist.

“PADCEV is the first and only FDA-approved therapy for patients with locally advanced or metastatic urothelial cancer who have received immunotherapy and cannot receive cisplatin,” said Roger Dansey, M.D., Chief Medical Officer, Seagen. “Because of the FDA’s Real-Time Oncology Review, we’re able to make PADCEV available as early as possible to these patients, who have limited treatment options due to their age or comorbid conditions.”

As Andrew Krivoshik, M.D., Ph.D., Senior Vice President and Oncology Therapeutic Area Head, Astellas, explained, “The FDA’s decision to convert accelerated approval to regular approval was based on data from the Phase 3 EV-301 trial, which had a primary endpoint of overall survival for patients treated with PADCEV versus chemotherapy. With PADCEV, for the first time, physicians can treat advanced urothelial cancer following treatment with a platinum-containing therapy and immunotherapy using an FDA-approved therapy that has demonstrated an overall survival benefit compared with chemotherapy.”

Padcev works by binding with the protein Nectin-4, which is prevalent on the surface of bladder cancer cells, and then releasing an anti-tumor chemical into the cell. The most common adverse reactions included rash, peripheral neuropathy, alopecia, fatigue, decreased appetite, anemia, diarrhea, pruritus, decreased weight, nausea, dry eye and dysgeusia. Still, this is the only drug available for advanced bladder cancer once chemotherapy has failed.

“Almost half of advanced bladder cancer patients cannot receive cisplatin-based chemotherapy. Many of these patients will receive first-line immunotherapy. If their cancer does not respond -- or if it progresses after prior response to immunotherapy -- there is an urgent need for more treatment options as there is currently no standard of care,” said Evan Y. Yu, M.D., Division of Oncology, Department of Medicine, University of Washington School of Medicine and a lead investigator for the EV-201 trial, in which all patients were previously treated with immunotherapy. “A new regulatory approval for enfortumab vedotin is an important clinical advance and can help serve this unmet need.”

Astellas and Seagen are co-developing enfortumab vedotin under a 50:50 worldwide development and commercialization collaboration agreement. In the United States, Astellas and Seagen co-promote enfortumab vedotin under the brand name PADCEV® (enfortumab vedotin-ejfv). In the Americas outside the US, Seagen holds responsibility for commercialization activities and regulatory filings. Outside of the Americas, Astellas holds responsibility for commercialization activities and regulatory filings.