On a roll, Gilead snags 2nd Trodelvy nod—in bladder cancer—but Seagen and Astellas have set the bar high

Trodelvy
Gilead Sciences has snagged FDA accelerated approval for Trodelvy in third-line bladder cancer. (Olivier Le Moal/Getty Images)

On the heels of turning a conditional FDA nod for Trodelvy in triple-negative breast cancer into a full one, Gilead Sciences has snatched a second green light for the antibody-drug conjugate, this time in bladder cancer. But thanks to competitive data from a rival, pharma watchers have low sales expectations for the new indication.

The FDA has granted accelerated approval of Trodelvy to treat patients with locally advanced or metastatic urothelial cancer who have tried two prior therapies, including a platinum-based chemo and a PD-1/L1 checkpoint inhibitor, Gilead said Tuesday.

Bladder cancer wasn’t a major driver in Gilead’s decision to spend $21 billion on Trodelvy’s developer, Immunomedics. But the drug could have had more opportunity if it weren’t for the even better clinical data that Seagen and partner Astellas recently posted for their own antibody-drug conjugate, Padcev.

Trodelvy earned its bladder cancer go-ahead with early results from the phase 2 Trophy-U-01 study. Of the 112 patients evaluable for efficacy, 27.7% responded to Trodelvy with significant tumor shrinkage, with responses lasting a median 7.2 months. Gilead’s now running a phase 3 confirmatory trial dubbed Tropics-04, hoping to show the drug can extend patients’ lives and convert the accelerated green light into a full one.

But Padcev already has all those data, and it appears to be more powerful than the Gilead med. In third-line bladder cancer, Padcev cut the risk of death by 30% over chemotherapy in the phase 3 EV-301 trial. As for tumor shrinkage, Padcev’s overall response rate stood at 40.6%, which appeared to be better than Trodelvy’s showing in its own trial, according to results updated at this year’s ASCO GU event.

RELATED: ESMO: New Trodelvy breast, bladder cancer data show why Gilead's going big for Immunomedics

While cross-trial comparisons have their intrinsic problems, analysts use them for competition analysis anyway. Based on those data, they had already declared Padcev the winner between the two in bladder cancer.

Two oncology experts labeled Padcev’s data as “practice changing” in third-line treatment and “were excited for the drug to move into earlier lines of therapy and to use the drug in combination with [Merck’s] Keytruda,” SVB Leerink analyst Andrew Berens wrote in an investor note right after the ASCO GU event in February.

As for Trodelvy, one expert “felt the enthusiasm was much more modest” in late-line bladder cancer, and both industry leaders expressed concern about the drug’s toxicity profile. Trodelvy bears a boxed warning for potentially life-threatening neutropenia and severe diarrhea.

RELATED: Gilead snags full Trodelvy breast cancer nod, but it needs more to make the $21B Immunomedics buy worthwhile

Gilead’s commercial focus for Trodelvy is expanding its use from academic medical centers—which generally have more experience managing serious side effects—into the community setting, Porges summarized in a separate February note after hosting Gilead Chief Commercial Officer Johanna Mercier and Chief Financial Officer Andrew Dickinson at an investor event. The company believes targeted education and emphasizing the survival benefit seen in the drug’s TNBC indication could help it increase share in the community setting, Porges said.

Investors’ focus is on Trodelvy’s upcoming phase 3 data in the much larger HR-positive, HER2-negative breast cancer indication, which are expected later this year. Another potential major upside for the drug lies in non-small cell lung cancer, with a phase 2 readout possible in 2022.

Analysts have previously questioned whether Gilead paid too much for Immunomedics. But the company believes it can justify that heavy investment if it achieves success in just one more disease between either HR-positive breast cancer or NSCLC, Porges noted.