Roche announced today that the United States (U.S.) Food and Drug Administration (FDA) has accepted the company’s New Drug Application for giredestrant, an investigational oral therapy, in combination with everolimus for the treatment of adult patients with oestrogen receptor (ER)-positive, human epidermal growth factor receptor 2-negative, ESR1-mutated locally advanced or metastatic breast cancer following recurrence or progression on a prior endocrine-based regimen. The FDA is expected to make a decision on the approval by 18 December 2026. Giredestrant plus everolimus could be the first and only oral selective oestrogen receptor degrader (SERD) combination approved in the post-cyclin-dependent kinase (CDK)4/6 inhibitor setting.
“The clinically meaningful benefit seen with giredestrant could enable an important new treatment option to help delay disease progression or death in people with advanced, ER-positive breast cancer,” said Levi Garraway, MD, PhD, Roche’s Chief Medical Officer and Head of Global Product Development. “This acceptance marks a first step towards establishing the giredestrant combination as a new standard of care in this population.”
The filing acceptance is based on the phase III evERA Breast Cancer study results, which showed that giredestrant plus everolimus reduced the risk of disease progression or death by 44% and 62% in the intention-to-treat (ITT) and ESR1-mutated populations, respectively, compared with standard-of-care endocrine therapy plus everolimus. In the ESR1-mutated population, the median progression-free survival (PFS) was 9.99 months compared with 5.45 months in the giredestrant and comparator arm, respectively (stratified hazard ratio [HR]=0.38, 95% CI: 0.27-0.54, p-value=<0.0001). In the ITT population, the median PFS was 8.77 months compared with 5.49 months in the giredestrant and comparator arms, respectively (HR=0.56, 95% CI: 0.44-0.71, p-value=<0.0001).
Overall survival (OS) data were immature at the time of analysis, but a clear positive trend has been observed in the ITT (HR=0.69, 95% CI: 0.47-1.00, p-value=0.0473) and ESR1-mutated populations (HR=0.62, 95% CI: 0.38-1.02, p-value=0.0566). Follow-up for OS will continue to the next analysis. Adverse events for the giredestrant combination were manageable and consistent with the known safety profiles of the individual medicines. No unexpected safety findings were observed, including no photopsia.
Data from evERA are being used to support filing submissions to other global health authorities.
ER-positive breast cancer accounts for approximately 70% of breast cancer cases.2 Resistance to endocrine therapies, particularly in the post-CDK inhibitor setting, increases the risk of disease progression and is associated with poor outcomes. Oral combination therapies, such as giredestrant plus everolimus, could address this by targeting two different signalling pathways while helping to minimise the impact of treatment on people’s lives without the need for injections.
evERA was the first positive phase III readout for giredestrant, followed by lidERA Breast Cancer in the early-stage setting. The scientific rationale for lidERA was supported by prior results in the neoadjuvant setting, including the coopERA trial showing that giredestrant was superior to an aromatase inhibitor in reducing malignant cell division (Ki67 levels). This growing body of evidence underscores the potential of giredestrant to become a new standard-of-care endocrine therapy across ER-positive early-stage and advanced breast cancer. In the coming weeks, Roche will submit the giredestrant phase III lidERA data in early-stage breast cancer to health authorities worldwide, including the FDA. The persevERA readout in first-line ER-positive breast cancer is expected in the first half of this year, which will provide further evidence for giredestrant in the ER-positive breast cancer treatment paradigm.
Our extensive giredestrant clinical development programme spans multiple treatment settings and lines of therapy, reflecting our commitment to deliver innovative medicines to as many people with ER-positive breast cancer as possible.
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