Indianapolis, Sept. 25, 2025 – In a landmark advancement for breast cancer treatment, the U.S. Food and Drug Administration (FDA) has approved Eli Lilly’s Inluriyo (imlunestrant) as a once-daily oral therapy for adults with estrogen receptor–positive (ER+), human epidermal growth factor receptor 2–negative (HER2–), ESR1-mutated advanced or metastatic breast cancer (MBC). This decision provides a critical new option for patients whose disease progressed following at least one line of endocrine therapy.
Science Significance
Inluriyo is a next-generation oral estrogen receptor (ER) antagonist that targets ESR1 mutations, which drive cancer growth in roughly half of ER+, HER2– MBC patients after aromatase inhibitor exposure. These mutations can activate estrogen receptors and cause resistance to standard hormone therapies.
In the pivotal Phase 3 EMBER-3 trial, Inluriyo reduced the risk of disease progression or death by 38% versus standard endocrine therapy, demonstrating a median progression-free survival (PFS) of 5.5 months compared with 3.8 months for fulvestrant or exemestane (HR=0.62 [95% CI: 0.46–0.82]; p=0.0008).
The drug binds to and degrades mutant estrogen receptors, delivering continuous ER inhibition to slow tumor growth and delay disease progression.
Regulatory Significance
The FDA’s decision was based on positive data from 256 ESR1-mutated MBC patients enrolled in EMBER-3, a Phase 3 randomized trial comparing Inluriyo monotherapy with fulvestrant or exemestane.
The majority of adverse events were low grade, and discontinuation due to adverse reactions occurred in only 4.6% of patients. The label includes a warning for embryo-fetal toxicity, requiring effective contraception during and after treatment.
The approval expands the therapeutic landscape for advanced breast cancer, positioning Inluriyo as a new standard of care for patients harboring ESR1 mutations.
Business Significance
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For Eli Lilly, this approval strengthens the company’s oncology portfolio and underscores its strategic focus on breast cancer innovation.
“This therapy reflects our commitment to developing treatments that improve outcomes for people with breast cancer and represents an important step toward advancing innovative, all-oral treatment approaches,” said Jacob Van Naarden, executive vice president and president of Lilly Oncology.
The company expects U.S. commercial launch of Inluriyo in the coming weeks, supporting potential blockbuster revenue as ESR1 testing becomes increasingly routine in breast cancer management.
Patients’ Significance
The approval offers a meaningful alternative for patients with ESR1-mutated metastatic breast cancer, a population with limited options and high unmet need.
Patients with this mutation often develop resistance to current endocrine therapies, making disease control difficult.
Inluriyo’s oral, once-daily dosing provides flexibility, convenience, and improved quality of life, reducing reliance on injectable treatments such as fulvestrant.
Patient advocacy groups welcomed the decision as a milestone that can help women manage their disease while maintaining daily routines.
Policy Significance
The approval of Inluriyo highlights the FDA’s continued prioritization of precision oncology, where treatments are matched to specific genetic drivers of disease.
It reinforces the importance of genomic testing for ESR1 mutations in guiding treatment selection for metastatic breast cancer, encouraging healthcare systems to adopt routine molecular diagnostics.
The decision may also influence reimbursement and testing policies, ensuring broader access to ESR1 testing and targeted therapies.
Transaction Highlights
Eli Lilly and Company announced that the U.S. Food and Drug Administration (FDA) has approved Inluriyo (imlunestrant) 200 mg tablets for the treatment of adults with estrogen receptor–positive (ER+), human epidermal growth factor receptor 2–negative (HER2–), ESR1-mutated advanced or metastatic breast cancer whose disease progressed following at least one line of endocrine therapy. The approval is supported by data from the Phase 3 EMBER-3 trial, which showed that Inluriyo monotherapy reduced the risk of disease progression or death by 38% compared to standard endocrine therapy, delivering a median progression-free survival of 5.5 months versus 3.8 months for fulvestrant or exemestane. The once-daily oral treatment demonstrated a favorable safety profile, with most adverse events reported as mild to moderate in severity and only 4.6% of patients discontinuing due to side effects. Eli Lilly plans to make Inluriyo available in the United States within the coming weeks, further expanding its oncology portfolio and strengthening its leadership in breast cancer therapeutics.
Source: Eli Lilly and Company Press Release
