FDA Accepts New Drug Application for Genentech’s Giredestrant in ESR1-Mutated, ER-Positive Advanced Breast Cancer

– Filing acceptance based on Phase III data showing giredestrant plus everolimus reduced the risk of disease progression or death by 44% and 62% in ITT and ESR1-mutated populations, respectively, versus standard-of-care endocrine therapy plus everolimus –

– Strength of evERA data demonstrate potential for giredestrant combination to help address resistance to standard-of-care therapies, and could be the first and only oral SERD combination approved in the post-CDK4/6 inhibitor setting –

– The FDA has set a Prescription Drug User Fee Act date of December 18 –

SOUTH SAN FRANCISCO, Calif.–(BUSINESS WIRE)–Genentech, a member of the Roche Group (SIX: RO, ROG; OTCQX: RHHBY), announced today that the 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 estrogen 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 December 18, 2026. Giredestrant plus everolimus could be the first and only oral selective estrogen 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, M.D., Ph.D., 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. 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 signaling pathways while helping to minimize 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, Genentech will submit the giredestrant Phase III lidERA data in early-stage breast cancer to 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 program 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.

About the evERA Breast Cancer study

evERA Breast Cancer [NCT05306340] is a Phase III, randomized, open-label, multicenter study evaluating the efficacy and safety of giredestrant in combination with everolimus versus standard-of-care endocrine therapy in combination with everolimus in people with estrogen receptor (ER)-positive, human epidermal growth factor receptor 2-negative locally advanced or metastatic breast cancer who have had previous treatment with cyclin-dependent kinase (CDK)4/6 inhibitor and endocrine therapy, either in the adjuvant or locally advanced/metastatic setting.

The co-primary endpoints are investigator-assessed progression-free survival in the intention-to-treat and ESR1-mutated populations, defined as the time from randomization to the time when the disease progresses or a patient dies from any cause. The trial has been enriched for ESR1-mutated patients above the natural prevalence to assess the efficacy in this population. In the post-CDK inhibitor setting, up to 40% of people with ER-positive disease have ESR1 mutations. Key secondary endpoints include overall survival, objective response rate, duration of response, clinical benefit rate and safety.

About giredestrant

Giredestrant is an investigational, oral, potent next-generation selective estrogen receptor degrader and full antagonist.

Giredestrant is designed to block estrogen from binding to the estrogen receptor (ER), triggering its breakdown (known as degradation) and stopping or slowing down the growth of cancer cells.

Giredestrant has an extensive clinical development program and is being investigated in five company-sponsored Phase III clinical trials that span multiple treatment settings and lines of therapy to benefit as many people as possible:

• Giredestrant versus standard-of-care endocrine therapy (SoC ET) as adjuvant treatment in ER-positive, human epidermal growth factor receptor 2 (HER2)-negative early-stage breast cancer (lidERA Breast Cancer; NCT04961996)
• Giredestrant plus everolimus versus SoC ET plus everolimus in ER-positive, HER2-negative, locally advanced or metastatic breast cancer (evERA Breast Cancer; NCT05306340)
• Giredestrant plus palbociclib versus letrozole plus palbociclib in ER-positive, HER2-negative, endocrine-sensitive, recurrent locally advanced or metastatic breast cancer (persevERA Breast Cancer; NCT04546009)
• Giredestrant plus investigator’s choice of a cyclin-dependent kinase (CDK)4/6 inhibitor versus fulvestrant plus a CDK4/6 inhibitor in ER-positive, HER2-negative advanced breast cancer resistant to adjuvant endocrine therapy (pionERA Breast Cancer; NCT06065748)
• Giredestrant plus dual HER2 blockade versus dual HER2 blockade in ER-positive, HER2-positive locally advanced or metastatic breast cancer (heredERA Breast Cancer; NCT05296798)

About estrogen receptor (ER)-positive breast cancer

Globally, the burden of breast cancer continues to grow, with 2.3 million women diagnosed and 670,000 dying from the disease every year. Breast cancer remains the number one cause of cancer-related deaths amongst women, and the second most common cancer type.

ER-positive breast cancer accounts for approximately 70% of breast cancer cases. A defining feature of ER-positive breast cancer is that its tumor cells have receptors that attach to estrogen, which can contribute to tumor growth.

Despite treatment advances, ER-positive breast cancer remains particularly challenging to treat due to its biological complexity. Patients often face the risk of disease progression, treatment side effects and resistance to endocrine therapy. There is an urgent need for more effective treatments that can delay clinical progression and reduce the burden of treatment on people’s lives.

About Genentech in Breast Cancer

Genentech has been advancing breast cancer research for more than 30 years with the goal of helping as many people with the disease as possible. Our medicines, along with companion diagnostic tests, have contributed to bringing breakthrough outcomes in multiple types of breast cancers. As our understanding of breast cancer biology rapidly improves, we are working to identify new biomarkers and approaches to treatment for other subtypes of the disease, including estrogen receptor-positive breast cancer, which is a form of hormone receptor-positive breast cancer, the most prevalent type of all breast cancers.

About Genentech

Founded 50 years ago, Genentech is a leading biotechnology company that discovers, develops, manufactures and commercializes medicines to treat patients with serious and life-threatening medical conditions. The company, a member of the Roche Group, has headquarters in South San Francisco, California. For additional information about the company, please visit http://www.gene.com.

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