Seattle Genetics gets ready to launch its second ADC after scoring bladder cancer OK with partner Astellas
Seattle Genetics and Astellas have scored a truly accelerated approval to deploy their armed antibody in second-line urothelial cancer, adding another prominent drug to the list of 2019 OKs that the FDA has been dishing out well ahead of schedule.
Padcev is how enfortumab vedotin will be known on the market, where it will be a new option for patients with locally advanced or metastatic urothelial cancer — the most common type of bladder cancer — following treatment with a PD-1/L1 inhibitor and a platinum-containing chemotherapy. Designated a “breakthrough” therapy by the FDA, it’s the first antibody-drug conjugate to be approved for this aggressive disease, the companies noted, and it’s also the first product Seattle Genetics will be bringing into the market since Adcetris.
The antibody in enfortumab vedotin hunts down and latches onto Nectin-4, a cell surface protein highly expressed in bladder cancer, then releases the chemo agent (attached with a linker) to kill the cells.
The approval is the culmination of a co-development pact that dates back to 2007, in which Seattle Genetics and Astellas are splitting the costs and profits 50/50. But they are not nearly done.
First, they need to complete the confirmatory Phase III, a 550-patient, placebo-controlled trial measuring overall survival as its primary endpoint and PFS as one of the secondaries. Regulators gave the green light after reviewing data from EV-201, a single-arm trial involving 125 patients, in which the confirmed objective response rate hit 44% (12% complete, 32% partial). Median duration of response was 7.6 months.
Having rolled out those numbers at ASCO this summer, the partners submitted their filings for accelerated approval in July, and two months later regulators moved the PDUFA date up to March 2020 by granting priority review and cutting the timeframe from 10 months to 6 months.
Then there’s the push to move the therapy up to frontline. Seattle Genetics turned up at ESMO to show off how their drug combined with Keytruda triggered an impressive 71% overall response rate in frontline patients — 32 of 45 patients — who were ineligible for chemo. The complete response rate came in at 13%. For reference, Keytruda monotherapy was approved in this setting two years ago with an objective response rate of 29%, including 7% complete responses — and there are concerns about low efficacy for PD-L1 negative patients.
The biotech did have to contend with some serious adverse reactions, including urinary tract infection, cellulitis, febrile neutropenia, diarrhea, sepsis, acute kidney injury, dyspnea, and rash. The side effects proved fatal in 3.2% of patients.
But for longtime CEO Clay Siegall, that won’t hurt their chances in a disease clearly still in need of new treatments. Seattle Genetics has already hired the sales force for Padcev — and they will be gearing up for lots more, including breast cancer drug tucatinib, now under priority review.