Astellas, Seagen pave the way for Padcev's global rollout with full confirmatory data for urothelial cancer in hand
Astellas and Seagen made a big splash with their Nectin-4 targeting therapy Padcev in late 2019, scoring a conditional FDA approval to target urothelial cancer. Now, the results are in for the confirmatory study for that indication, and it looks like a resounding win for Padcev.
Astellas and Seagen’s Padcev extended patients’ lives to an average 12.9 months compared with nine months for a chemo control, according to full data from the Phase III EV-301 study presented Friday at the virtual ASCO GU meeting.
Results from the EV-301 trial showed Padcev administered after platinum-based chemo and a prior PD-1 therapy significantly extended OS, with a sparkling p-value of 0.001. On the study’s secondary endpoints, Padcev also significantly boosted progression-free survival, overall response rate and disease control rate over chemo. Median PFS was 5.6 months for the Padcev arm compared with 3.7 months for the chemo control.
Top-line data from EV-301 was unveiled back in September and showed a 30% reduction in risk of death (p = 0.001) and 39% reduction in risk of disease progression or death (p<0.00001). The latest data was jointly published Friday in the New England Journal of Medicine.
With the full confirmatory data in hand, the partners are aiming to file for a complete FDA approval by the end of March and then roll out submissions into targeted markets around the globe, the company said in a release. Padcev, an antibody-drug conjugate, currently sports an accelerated approval from the FDA as the first therapy of its kind to target the Nectin-4 protein.
Backing those submissions are data from a second cohort in the Phase II EV-102 trial, which were also unveiled Friday. In the second half of the single-arm EV-201 — the first half was used as the basis for the FDA’s accelerated approval in December 2019 — Padcev was tested on urothelial cancer patients who had received a prior PD-1/L-1 inhibitor but who had not received prior platinum-based chemo and were ineligible for cisplatin due to preexisting co-morbidities.
In that setting, 52% of patients who received Padcev had an objective response with a median duration of response of 10.9 months. Twenty percent of Padcev patients had a complete response, and 31% had a partial response. The partners plan to submit EV-201 as part of their FDA application in March and will pick and choose where to submit those data for global regulatory reviews.
In EV-201, 17% of all Grade 3 side effects were skin reactions, which will lead Astellas and Seagen to pen a “Dear HCP” letter as part of an effort to update prescribing information on the therapy, said Andy Krivoshik, an Astellas senior VP and head of the oncology therapeutic area. Padcev’s label includes a warning for skin reactions, citing 54% of patients in the pivotal trial showed a skin reaction to treatment.
“Even though Nectin-4 is known to be expressed in the skin and is called out in the USPI, as we’re working with regulators we want to make sure this is something that’s called out to prescribers in particular,” he told Endpoints News.
After following through in late-stage urothelial cancer, Krivoshik said the teams at Astellas and Seagen are looking for opportunities to take Padcev into early stages of the disease as well as in other tumor types with high Nectin-4 expression.
One of those early-stage efforts — a combo study alongside PD-(L)1 inhibitor Keytruda from Merck — could eventually bear fruit and build a case for the ADC class on the whole in earlier settings. Ultimately, however, the partners are most focused on breaking ground for underserved patients, Krivoshik said.
“We really look for areas where there are high unmet need,” he said.
Editor’s Note: This story has been updated to correct an error. Astellas and Seagen’s “Dear HCP” letter is not tied to its FDA submission packet.