Gilead: Trial Failure, Withdraws Approval of Trodelvy for Bladder Cancer Treatment

On October 18, 2024, Gilead announced, after consultations with the FDA, that it would voluntarily withdraw the accelerated approval of Trodelvy for treating adult patients with locally advanced or metastatic urothelial cancer who had previously received platinum-containing chemotherapy and PD-1/PD-L1 antibody therapy in the United States.

Gilead clarified that the drug's other U.S.-approved indications for breast cancer remain unaffected. 

This withdrawal is not surprising. As early as May, Gilead had indicated that the TROPiCS-04 study, which served as the confirmatory trial for Trodelvy's conditional approval in bladder cancer, had failed to meet its expected goals. This TROP2-targeting antibody-drug conjugate did not demonstrate superiority over chemotherapy in extending the lives of bladder cancer patients who had undergone PD-1/L1 therapy and chemotherapy. Detailed data regarding this failure has yet to be disclosed.

Trodelvy was approved for bladder cancer in 2021 based on data from a Phase II single-arm study, in which the drug produced a tumor response in 27.7% of patients, with 5.4% achieving complete response. The median duration of response was 7.2 months. 

Bladder cancer is a relatively small indication for Trodelvy, accounting for less than 10% of the drug's sales, according to Gilead's Chief Financial Officer Andrew Dickinson during the company’s Q2 earnings call in August. In 2023, Trodelvy (sacituzumab govitecan) generated $1.063 billion in sales, a 56% year-over-year increase. However, the failure in bladder cancer followed another more significant setback: Trodelvy failed to show effectiveness in a second-line non-small cell lung cancer (NSCLC) trial comparing it with chemotherapy. Following the setback in the EVOKE-01 trial, Gilead confirmed a $2.4 billion asset impairment loss. Trodelvy was once the crown jewel of Gilead's $21 billion acquisition of Immunomedics in 2020. 

These two trial failures have cast a shadow over Trodelvy, once seen as the cornerstone of Gilead’s solid tumor business.

Meanwhile, Trodelvy’s first-mover advantage in the market has also been weakened as two competitors are advancing their own TROP2 antibody-drug conjugates. AstraZeneca and Daiichi Sankyo, as well as Merck and Kelun-Biotech, are both conducting large-scale Phase III trials.

The next significant data release for Trodelvy will be from the EVOKE-03 trial, which is testing Gilead’s drug in combination with Merck's PD-1 inhibitor Keytruda in PD-L1 high-expressing NSCLC. This trial began in February 2023, with a primary completion date expected in January 2027.

In China, companies such as Kelun-Biotech, Junshi Biosciences, Doer Biologics, InnoCare, Mabwell, BrightGene, and Hengrui Pharmaceuticals are developing TROP2 ADCs.

Image source: https://www.fiercepharma.com/pharma/gilead-withdraws-trodelvy-bladder-cancer-after-trial-flop