Gilead Announces Positive Top-Line Results from Phase 3 TROPiCS-02 Trial of Trodelvy in HR+/HER2- Metastatic Breast Cancer

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This Monday, Gilead Sciences announced the results of the Phase 3 TROPiCS-02 study for Trodelvy. The data showed that in HR+/HER2- metastatic breast cancer patients, Trodelvy outperformed chemotherapy in preventing disease progression or death. Gilead stated that the study met its primary endpoint, with a "statistically significant" improvement in progression-free survival (PFS). However, Gilead did not provide a straightforward answer regarding whether the PFS benefit, which investors are closely watching, has "clinical significance."

Gilead said in a securities filing: "There are broad views on what constitutes 'clinical significance' in this population. We are evaluating the data and will explore with regulators potential pathways to bring Trodelvy to patients."

RBC Capital Markets analyst Brian Abrahams wrote in a Monday report that Gilead's description raised "considerable uncertainty" about whether the results are clinically meaningful for patients.

Under Daniel O’Day's leadership, Gilead Sciences is expanding its product portfolio with a new focus on oncology. The company aims for one-third of its revenue to come from oncology by 2030, while in 2021, oncology revenue accounted for only 4.6%.

Trodelvy is a TROP2-targeted ADC that Gilead acquired when it purchased Immunomedics for $21 billion in September 2020. This drug is a key pillar of its oncology program.

Brian Abrahams noted in an August 2021 report that the TROPiCS-02 study held significant "validation" potential within the Trodelvy development program, as it would not only validate this major acquisition but also affirm Gilead Sciences' long-term oncology platform and plans.

Brian Abrahams said at the time that if Trodelvy demonstrates good efficacy and safety in the overall HR+/HER2- breast cancer population, its global annual sales peak could reach $2.2 billion.

Despite the less-than-optimistic data, Gilead stated that this would not affect the plan to advance studies in earlier-stage patients. Gilead remains confident in its 2030 oncology revenue target, stating that the goal is "risk-adjusted and considers the nature of our business, where our portfolio can generate a range of outcomes."

Previously, Gilead's postponement of the release of TROPiCS-02 study data from the second half of 2021 to the first quarter of 2022 had already made some investors uneasy. Brian Abrahams stated in a report last week that a recent survey by RBC showed 73% of investors had expected Trodelvy to demonstrate a PFS benefit that would be statistically significant but lack clinical meaningfulness.

Gilead stated that the TROPiCS-02 study aimed to reduce the risk of disease progression or death by 30%. Brian Abrahams pointed out that this could imply a hypothetical absolute median difference in PFS of 1.6 months, with Trodelvy at 5.3 months and chemotherapy at 3.7 months. However, Gilead noted that even with a 0.9-month difference in median PFS, the study was still capable of detecting a statistically significant difference.

In a press release issued on Monday, Gilead did not disclose the exact figures for PFS or the extent of risk reduction, stating that these would be announced at an upcoming medical conference. However, the company noted that the results were consistent with those observed in the HR+/HER2- patient subset from the Phase 1/2 IMMU-132-01 study. In this earlier study, the PFS for HR+/HER2- breast cancer patients was 5.5 months.

Combining these details, Brian Abrahams estimated that the actual difference in PFS might be between 0.9 months and 1.8 months, meaning Trodelvy may not reach the improvement of at least 2 months hoped for by industry observers. Patients enrolled in the TROPiCS-02 study had received endocrine therapy, CDK4/6 inhibitors, and 2-4 lines of chemotherapy prior to Trodelvy.

Gilead Sciences stated that the study showed a favorable trend in the first interim analysis, indicating that Trodelvy could extend patients' lives. The study permits a second interim overall survival analysis, with final results expected in 2024. Brian Abrahams noted that, based on the current data, submitting an application is unlikely.

Trodelvy is a first-in-class TROP-2 targeted antibody-drug conjugate (ADC), composed of a humanized IgG1 antibody targeting the TROP-2 antigen linked to SN-38, the metabolically active product of the chemotherapy drug irinotecan (a topoisomerase I inhibitor). It has been approved for two indications: (1) for the treatment of adult patients with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC) who have received at least two prior therapies, with at least one therapy for metastatic disease; (2) for the treatment of adult patients with locally advanced or metastatic urothelial cancer (UC) who have previously received platinum-based chemotherapy and treatment with a PD-1 inhibitor or PD-L1 inhibitor.

In April 2019, Everest Medicines entered into an agreement with Immunomedics to acquire the rights to Trodelvy in Greater China, South Korea, Mongolia, and Southeast Asian countries and regions. In February 2022, Trodelvy received approval in Singapore for the treatment of adult patients with TNBC, marking the first new drug approval for Trodelvy in Everest Medicines' licensed territory. The company anticipates that Trodelvy will receive additional approvals in various countries and regions within the licensed territory over the next year.

Reference Source: Gilead drops unclear win for key Trodelvy breast cancer trial, poking holes in CEO’s oncology