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Seagen, Astellas eye fast FDA review for Padcev’s expanded bladder cancer use, with all-important Keytruda combo data to come

Seagen and Astellas have stepped in the FDA fast lane to move Padcev into earlier bladder cancer treatment—and one step closer to the antibody-drug conjugate’s blockbuster forecast.

The FDA put two Padcev bladder cancer applications under priority review, the companies said Monday. One would turn the drug’s conditional nod in patients who’ve received two prior therapies into a full one. The other would expand the drug into second-line treatment for patients ineligible for cisplatin chemotherapy.

SVB Leerink analyst Andrew Berens has put Padcev’s peak sales at $1.32 billion across all its potential indications in previously treated bladder cancer. But compared with the main course of front-line use, the approval in cancer that’s recurred is simply an appetizer.

Padcev’s currently allowed to treat patients who’ve already taken a PD-1/L1 inhibitor and a platinum-based chemotherapy, based on tumor shrinkage data from the phase 2 EV-201 trial. Data from the phase 3 EV-301 trial recently showed the drug slashed the risk of death by 30% compared with chemo. And that could convert the accelerated approval in third-line treatment into a regular one.

Then in cohort 2 of the EV-201 study, Padcev triggered a response in 52% of patients who had received a PD-1/L1 inhibitor but weren’t eligible to get cisplatin—and eliminated any sign of tumor in 20% of those who responded, according to data presented at this year’s ASCO GU event. The two companies hope the data will be enough to support a conditional second-line go-ahead.

In bladder cancer, Padcev is generally viewed as a better drug than Gilead Sciences’ newly approved antibody-drug conjugate Trodelvy; Padcev’s tumor response data looked better than Trodelvy’s in their separate trials. Even though the data aren’t supposed to be compared directly with each other, industry watchers figure Padcev would be used earlier and for longer, while Trodelvy could help patients who’ve failed after Padcev. 

For 2021, Seagen has projected Padcev sales between $310 million and $325 million, with some sales in the new second-line setting.

The drug recently had a safety scare, as fatal skin reactions called Stevens-Johnson syndrome and toxic epidermal necrolysis cropped up in Padcev patients. Although the new post-marketing finding could trigger FDA label changes, their effects on commercial demand will be limited, Berens predicted in a February note after talking to physicians.  

While previously treated bladder cancer itself represents a blockbuster opportunity, the newly diagnosed setting could be a much larger market—as much as $7.48 billion in Padcev peak sales, according to Berens.

To get there, Padcev is being paired with Merck’s PD-1 king Keytruda in cohort K of the EV-103 trial. Seagen expects the study to finish enrollment this year to support a potential accelerated approval in 2022.