Eli Lilly has won the second FDA approval for an oral selective estrogen receptor degrader (SERD).
Like the first oral SERD, Lilly’s imlunestrant is only cleared to treat ER-positive, HER2-negative advanced breast cancer that carries ESR1 gene mutations. Patients need to have tried at least one line of endocrine therapy to be eligible for imlunestrant, which will be sold under the brand name Inluriyo.
“This represents an important advancement for patients with ESR1-mutated [metastatic breast cancer], a mutation found in nearly half of patients who have taken hormone therapies, often contributing to treatment resistance,” Komal Jhaveri, M.D., section head of endocrine therapy research and clinical director of early drug development at Memorial Sloan Kettering Cancer Center, said in a Sept. 25 release.
Jhaveri is a principal investigator of the phase 3 Ember-3 trial, which supported Inluriyo’s approval. In the study, Inluriyo significantly reduced the risk of progression or death by 38% versus standard endocrine therapy in patients with ESR1-mutated ER-positive, HER2-negative breast cancer following progression on an aromatase inhibitor.
While the study also recruited patients without ESR1 mutations, it failed to meet the progression-free survival efficacy bar in all patients.
Before Lilly, Italian drugmaker Menarini had secured the first FDA approval for an oral SERD, also in ESR1-mutated breast cancer.
Development of oral SERDs has quickly taken off as drugmakers hope to build on the success of AstraZeneca’s injectable SERD Faslodex.
AZ recently reported a positive phase 3 for its oral SERD candidate camizestrant. The company’s Serena-6 trial adopts a novel design that incorporates camizestrant midway of first-line treatment after ESR1 mutation is detected and before disease progression.
The British pharma has listed a regulatory decision based on Serena-6 as a first-half 2026 event in its second-quarter report in July. The company has a separate phase 3 trial, Serena-4, in a more traditional first-line setting that combines camizestrant with Pfizer’s CDK4/6 inhibitor Ibrance, with a readout expected in the second half of 2026.
Lilly’s Inluriyo already has CDK4/6 combo data. In the same Ember-3 trial, a combination of Inluriyo and Lilly’s Verzenio led to a 43% reduction in the risk of death versus Inluriyo alone among patients with or without ESR1 mutations. In a subgroup of patients without the biomarker, the combo’s disease progression benefit was still strong at 41%.
Because the combo arm was added to Ember-3 a few months after the study’s launch, data in this group were arguably less mature. At 15% data maturity, results on overall survival favored Inluriyo monotherapy over the Verzenio-Inluriyo combo in all patients regardless of ESR1 status.
Lilly only filed Inluriyo as a monotherapy, a company spokesperson confirmed to Fierce Pharma.
“Because the combination arm of the study began later than the monotherapy arm, those results are still maturing,” the spokesperson said. “Lilly has completed an updated analysis, which will be shared with the FDA and presented at a medical meeting later this year.”
Meanwhile, Roche on Monday revealed that its oral SERD candidate giredestrant, used in combination with everolimus, improved progression-free survival in ER-positive, HER2-negative breast cancer patients who had tried a CDK4/6 inhibitor and endocrine therapy.
The phase 3 evERA trial met both its co-primary endpoints as the combo showed “statistically significant and clinically meaningful” disease progression benefits in both the ESR1-mutated subgroup and the overall trial population, according to Roche. However, it remains to be seen whether the showing in all comers was driven by the ESR1 group.