Gilead's Trodelvy Faces Setback with Bladder Cancer Trial Failures and Early Death Concerns

In recent developments, Gilead Sciences has encountered another significant challenge with its drug Trodelvy in a phase 3 trial for bladder cancer. This comes after an earlier setback this year in a non-small cell lung cancer (NSCLC) study. Trodelvy, aimed at targeting TROP2, did not outperform single-agent chemotherapy in extending the survival of patients with urothelial cancer who had previously undergone chemotherapy and PD-1/L1 therapy.

The TROPiCS-04 study results could have serious implications for Gilead, potentially leading to the withdrawal of Trodelvy's accelerated approval in 2021 for previously treated bladder cancer. This could also weaken Gilead's competitive stance against other TROP2 antibody-drug conjugates (ADCs) being developed by Merck and the AstraZeneca/Daiichi Sankyo partnership.

Gilead is currently analyzing the data and plans to discuss the trial results and future steps with the FDA. Trodelvy had initially gained accelerated approval based on a study that showed a 27.7% response rate in patients treated with chemo and PD-1/L1 therapies. However, the recent trial only demonstrated a numerical, not statistically significant, improvement in patient survival compared to single-agent chemotherapy. Additionally, the study reported a higher number of deaths due to adverse events linked to Trodelvy, particularly neutropenia-related complications early in treatment.

Neutropenia is already noted in a boxed warning on Trodelvy’s label. Gilead has emphasized the importance of using G-CSF to prevent such complications and is working to communicate this to healthcare providers.

This failure in the bladder cancer trial adds to a series of disappointments for Trodelvy. In 2022, the drug faced scrutiny over its benefits in HR-positive, HER2-negative breast cancer, despite a positive outcome in the TROPiCS-02 trial. However, the results were overshadowed by AstraZeneca and Daiichi Sankyo's significant HER2-low win for Enhertu. Consequently, Gilead had to account for $2.7 billion in impairment charges related to Trodelvy.

Earlier this year, Trodelvy also underperformed in the phase 3 EVOKE-01 trial against chemotherapy in previously treated NSCLC, leading Gilead to incur an additional $2.4 billion in impairment charges.

These ongoing clinical struggles come as Gilead faces competition from other TROP2 ADCs. Merck's sacituzumab tirumotecan, licensed from China’s Kelun-Biotech, has not yet disclosed phase 3 data. Meanwhile, AstraZeneca and Daiichi Sankyo’s datopotamab deruxtecan is undergoing FDA review for HR-positive, HER2-negative breast cancer and nonsquamous NSCLC, though neither has phase 3 trials in bladder cancer, according to ClinicalTrials.gov.

Trodelvy’s recent failure starkly contrasts with the success of Pfizer and Astellas’ Nectin-4 ADC Padcev. Combined with Merck’s Keytruda, Padcev showed significant overall survival benefits in first-line bladder cancer. Padcev received accelerated approval in 2019 and full FDA approval in 2021.

With Trodelvy's diminishing appeal and slowing sales in Gilead’s cell therapy department, the company’s objective to derive a third of its revenue from oncology by 2030 appears increasingly uncertain.

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