Roche’s Giredestrant Wins FDA Priority Review for Early Breast Cancer

Roche has moved closer to delivering giredestrant to patients with early-stage breast cancer after the U.S. Food and Drug Administration (FDA) accepted its New Drug Application (NDA) under Priority Review. The filing covers adjuvant treatment of adults with stage I–III estrogen receptor (ER)-positive, HER2-negative breast cancer and is supported by Phase 3 data showing the investigational oral selective estrogen receptor degrader (SERD) reduced the risk of invasive disease recurrence or death by 30% compared with standard endocrine therapy.

The FDA has assigned a Prescription Drug User Fee Act (PDUFA) target action date of November 30, 2026.

Clinical Trial Evidence

The NDA is based on results from the Phase 3 lidERA Breast Cancer trial (NCT04961996), which enrolled more than 4,100 patients with medium- or high-risk stage I–III ER+/HER2– breast cancer.

The study met its primary endpoint, demonstrating a 30% reduction in the risk of invasive disease recurrence or death versus standard endocrine therapy (HR=0.70; 95% CI: 0.57–0.87; p=0.0014). At three years, 92.4% of patients receiving giredestrant remained alive and free of invasive disease compared with 89.6% of those on standard therapy, with consistent benefit across clinically relevant subgroups.

Overall survival data remain immature, though investigators reported an encouraging positive trend. FDA approvals in the adjuvant setting are typically based on invasive disease-free survival, with overall survival follow-up required post-marketing.

Safety findings were favorable and consistent with the known profile of giredestrant. Treatment discontinuation occurred in 5.3% of patients receiving giredestrant compared with 8.2% of those on standard endocrine therapy, suggesting improved treatment persistence.

Scientific Context and Unmet Need

Giredestrant is a next-generation oral SERD that both antagonizes and degrades the estrogen receptor, blocking estrogen-driven tumor growth. By eliminating the receptor itself, the therapy may provide more complete suppression of estrogen signaling than conventional endocrine approaches.

ER-positive disease accounts for approximately 70% of breast cancer cases worldwide, and the majority of patients are diagnosed at an early stage. Despite advances in treatment, up to one-third of patients relapse during or after 5–10 years of adjuvant endocrine therapy.

The last major advance in adjuvant endocrine therapy came with the introduction of aromatase inhibitors in the early 2000s, highlighting the potential significance of giredestrant if approved.

Clinical Progress and Future Directions

Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development, described giredestrant as the first major endocrine therapy advance in early-stage ER-positive breast cancer in decades. He noted that FDA acceptance brings the company closer to delivering a potential new standard of care for patients with curable-stage disease.

Roche continues to advance a broad clinical development program for giredestrant, with five ongoing Phase 3 studies spanning early-stage, locally advanced, and metastatic ER-positive breast cancer.

The FDA has also accepted an NDA for giredestrant in combination with everolimus for ESR1-mutated ER-positive advanced breast cancer, with a regulatory decision expected in December 2026.

With two Priority Review applications currently under FDA evaluation, Roche is positioned to potentially establish giredestrant as a cornerstone therapy across both early-stage and advanced ER-positive breast cancer, reshaping the endocrine treatment landscape globally.

Reference

FDA accepts New Drug Application for Roche’s giredestrant in ER-positive early-stage breast cancer, the first and only oral SERD with positive phase III results in the curative setting