Gilead's Trodelvy Misses Primary Goal in Confirmatory Trial

Gilead Sciences recently disclosed that its antibody-drug conjugate, Trodelvy, did not meet the primary endpoint in a Phase III TROPiCS-04 study for patients with locally advanced or metastatic urothelial cancer (mUC). This marks another challenge for the treatment, which has been under scrutiny.

The TROPiCS-04 trial aimed to compare Trodelvy to physician-selected single-agent chemotherapy treatments in mUC patients who had previously received both platinum-based chemotherapy and an anti-PD-(L)1 therapy. The primary endpoint evaluated was overall survival (OS) in the intention-to-treat (ITT) population. Unfortunately, the study did not meet this critical endpoint.

Despite failing to meet the primary endpoint, Gilead highlighted a "numerical improvement" in OS favoring Trodelvy, as well as positive trends in certain pre-specified subgroups. Secondary endpoints, including progression-free survival (PFS) and overall response rate (ORR), also demonstrated some improvement, although specific data were not immediately available. Gilead plans to present the full results at an upcoming medical conference.

Notably, the trial also reported a higher number of deaths in the Trodelvy cohort due to adverse events. While the exact numbers were not disclosed, Gilead mentioned that these deaths primarily occurred early in the treatment process and were related to "neutropenic complications," including infection.

In response to the trial results, Gilead is conducting a thorough investigation and will discuss the findings with the FDA to determine the next steps. The company emphasized the importance of using granulocyte-colony stimulating factor (G-CSF) to prevent neutropenic complications. It was noted that there have been no changes to Trodelvy’s safety profile for its approved use in breast cancer, although the drug carries a boxed warning for severe or life-threatening neutropenia.

Trodelvy has an accelerated approval for patients with mUC, but its continued approval in this indication depends on the verification and description of clinical benefits in confirmatory trials.

An analyst report from the Bank of Montreal Capital Markets pointed out that bladder cancer contributes a smaller portion of Trodelvy’s revenue, yet the study results raise concerns regarding further expansion into mUC. Jefferies analysts also commented on investor sentiment, noting that Gilead's stock has been under pressure, especially following a recent Phase III trial for non-small cell lung cancer in January 2024, where Trodelvy also failed to meet the primary endpoint of improving OS significantly.

The continued challenges in Gilead’s pipeline have sparked discussions among investors and hedge funds about the company's overall strategy and business development success compared to other large pharmaceutical companies.