After falling short in a confirmatory clinical trial, Gilead Sciences has decided to withdraw Trodelvy as a bladder cancer treatment in the U.S.
The California biotech announced the decision Friday following its discussions with the FDA. The move affects the accelerated approval for Trodelvy in advanced urothelial cancer patients who have previously received a PD-1/L1 inhibitor and chemotherapy.
The drug’s other U.S. indications in breast cancer remain in place, Gilead said.
The withdrawal wasn’t a surprise. Back in May, Gilead said the TROPiCS-04 study, which was meant to serve as the confirmatory trial for the conditional bladder cancer nod, didn’t hit its goal. The TROP2-directed antibody-drug conjugate failed to top chemotherapy at extending the lives of bladder cancer patients who had tried a PD-1/L1 therapy and chemo. Detailed data of that flop have not been shared yet.
Trodelvy earned its bladder cancer nod in 2021 based on single-arm, phase 2 data showing the drug triggered a tumor response in 27.7% of patients, including 5.4% who experienced a complete response. The median duration of response was 7.2 months.
Bladder cancer is a relatively small indication for Trodelvy, representing less than 10% of the drug’s sales, Gilead’s chief financial officer Andrew Dickinson said on the company’s second-quarter earnings call in August. In the three months ended in June, the first-in-class TROP2 ADC brought Gilead $320 million in sales.
However, the bladder cancer flop came on the back of another more important trial failure, in which Trodelvy failed to move the needle in second-line non-small cell lung cancer (NSCLC) when pitted against chemo. Following the setback in that study, called EVOKE-01, Gilead recognized an impairment charge of $2.4 billion. Trodelvy was the crown jewel in Gilead’s $21 billion acquisition of Immunomedics in 2020.
The two trial flops have cast a dark cloud over Trodelvy, which was touted as the cornerstone of Gilead’s solid tumor franchise. They also eroded Trodelvy’s first-to-market advantage as two rival partnerships, one between AstraZeneca and Daiichi Sankyo and the other between Merck & Co. and Kelun Biotech, are advancing their own TROP2 ADC offerings with expansive phase 3 programs.
Trodelvy’s next big NSCLC readout is EVOKE-03, which is testing the Gilead drug with Merck’s PD-1 inhibitor Keytruda in PD-L1-high NSCLC. Started in February 2023, the trial currently bears a primary completion date in January 2027. ASCENT-03, a phase 3 study that could move Trodelvy up into first-line triple-negative breast cancer in certain patients, is expected to read out this year.
Meanwhile, Trodelvy’s withdrawal in bladder cancer comes as the first-line bladder cancer treatment shifts to a combination of Keytruda and Pfizer and Astellas’ Nectin-4 ADC Padcev. This ongoing transition raises new questions around Trodelvy’s potential position in a post-PD-1/L1-and-chemo setting.
Facing heightened scrutiny from the FDA, biopharma companies appear to be more compliant with their timely withdrawals of accelerated approvals after confirmatory trial failures. Back in late 2022, GSK pulled the multiple myeloma ADC Blenrep from the U.S. market merely days after announcing a phase 3 trial flop. The British pharma is now aiming to reintroduce the drug in earlier treatment settings after two positive phase 3 readouts.
Last year, Takeda decided to voluntarily pull its lung cancer med Exkivity about two months after receiving negative confirmatory evidence.
And, last month, Pfizer abruptly announced a global market withdrawal of its sickle cell disease drug Oxbryta after data showed that patients had even more acute pain crises—a symptom of the disease—on the drug than they did before, as well as more deaths among Oxbyrta takers compared with a placebo.
Editor's Note: The story was updated to include information about ASCENT-03.