Gilead Sciences Withdraws Trodelvy; Bladder Cancer Treatment Failure Results in $21 Billion Investment Down the Drain

Following a disappointing confirmatory clinical trial, Gilead Sciences has officially decided to withdraw its product Trodelvy from the bladder cancer treatment market in the United States. The decision was announced Friday by the California-based biotechnology company after extensive discussions with the U.S. Food and Drug Administration (FDA). This directly affected the accelerated approval status of Trodelvy in a specific patient population - those with advanced urothelium carcinoma who had previously received PD-1/L1 inhibitors and chemotherapy.

Gilead emphasized that despite the setbacks in bladder cancer, Trodelvy remains effective in other indications for breast cancer in the United States.

The divestment did not come without warning. Back in May, Gilead had already heralded the substandard results of the troics-04 study, which was intended as a confirmative trial for Trodelvy in bladder cancer. Specifically, the TROP2-directed antibo-drug conjugate failed to demonstrate efficacy over conventional chemotherapy in extending survival in certain bladder cancer patients. So far, details about the failed test have not been made public.

Looking back at history, Trodelvy received approval for a bladder cancer treatment in 2021 based on positive data from a single-arm Phase 2 clinical trial. At that time, the drug triggered a tumor response in 27.7 percent of patients, with 5.4 percent achieving a complete response and a median response duration of 7.2 months.

Gilead's chief financial officer, Andrew Dickinson, noted during the company's second-quarter earnings call in August that bladder cancer treatment is a relatively small part of Trodelvy's many indications, contributing less than 10% of sales. The first-of-its-kind TROP2 ADC drug generated $320 million in sales for Gilead in the three months ended June.

It is important to note that Trodelvy's failure in the bladder cancer field was not an isolated incident, it came on the heels of the failure of another key trial, the IUX-01 study. Trodelvy also failed to achieve significant results in a trial comparing chemotherapy with second-line non-small cell lung cancer (NSCLC). As a result of the setback, Gilead took a $2.4 billion impairment charge. Trodelvy's performance has been highly anticipated as a core asset in Gilead's $21 billion acquisition of Immunomedics in 2020.

The successive failures of two important trials have certainly clouded Trodelvy's prospects. Once upon a time, Trodelvy was expected to be the cornerstone of Gilead's solid tumor franchise. However, as competitors such as Astrazeneca and Daiichi Sankyo, Merck and Kelun Biotech advance their respective TROP2 ADCs and pursue extensive Phase III programs, Trodelvy's first-mover advantage is gradually being eroded.

Looking ahead, Trodelvy's next major milestone will be the results of the IUX-03 trial. The trial is evaluating Gilead's drug in combination with Merck's PD-1 inhibitor Keytruda in patients with NSCLC with high PD-L1 expression. The trial started in February 2023 and is expected to be primarily completed in January 2027.

At the same time, with the shift in first-line bladder cancer treatment options - particularly Keytruda in combination with Pfizer and Astellas Nectin-4 ADC drug Padcev in favor - Trodelvy's exit from the bladder cancer space is particularly notable. This shift has sparked a new round of discussion about Trodelvy's status as a PD-1/L1 inhibitor and post-chemotherapy treatment.

Faced with an increasingly stringent regulatory review environment by the FDA, biopharmaceutical companies often tend to act quickly after the failure of confirmatory trials to withdraw expedited approval of related products. There have been several examples of this trend in recent years: GlaxoSmithKline withdrew its multiple myeloma ADC from Blenrep just days after its Phase 3 trial failed; Takeda voluntarily withdrew its lung cancer drug Exkivity about two months after receiving negative confirmation; And last month Pfizer abruptly pulled its sickle cell drug Oxbryta from global shelves over safety data.