Lilly Wins FDA Approval for Inluriyo-Verzenio Combination in Breast Cancer, Intensifying Competition

Eli Lilly has received U.S. Food and Drug Administration (FDA) approval for the combination of the oral selective estrogen receptor degrader (SERD) Inluriyo and the CDK4/6 inhibitor Verzenio.

According to Fierce Pharma on the 19th (local time), the FDA approved the Inluriyo-Verzenio combination for patients with estrogen receptor-positive (ER+) and human epidermal growth factor receptor 2-negative (HER2-) breast cancer harboring ESR1 mutations who have received prior treatment.

This expanded indication builds on the approval of Inluriyo monotherapy about 1 year ago. Inluriyo monotherapy is used to treat patients with ESR1-mutated ER+ and HER2- breast cancer.

In the phase 3 EMBER-3 trial, the median progression-free survival (PFS) was 11.1 months in patients who received the Inluriyo-Verzenio combination, compared with 5.5 months in the Inluriyo monotherapy group. The risk of disease progression or death was reduced by 47%.

Although these PFS data were released in December 2024, the FDA initially approved only the monotherapy because the overall survival (OS) data were not sufficiently mature. Jake Van Naarden, president of Lilly Oncology, said OS is currently "moving in the right direction."

Van Naarden told Fierce Pharma that, based on the longer PFS, he expects most patients to choose the combination over oral SERD monotherapy.

The approval also targets AstraZeneca’s competing drug Itacama. Earlier this month, the FDA granted accelerated approval to Itacama for use with a CDK4/6 inhibitor.

Itacama uses a new approach in which patients remain on their existing first-line treatment and switch therapies when an ESR1 mutation is detected, before radiographic disease progression. This requires monitoring for ESR1 mutations through blood tests.

In a statement, Van Naarden emphasized that the Inluriyo-Verzenio combination "does not introduce monitoring requirements that are burdensome for patients or physicians."

In AstraZeneca’s phase 3 SERENA-6 trial, the median PFS with the Itacama combination was 16 months, compared with 9.2 months in the first-line patient group that continued its existing treatment. Lilly’s EMBER-3 recorded a median PFS of 11.1 months in the second-line setting.

The two trials involved separate studies and patient populations and cannot be directly compared. However, Lilly argues that waiting for clinical progression before switching treatment may maximize the total duration of disease control.

Van Naarden said, "Early blockade may sound appealing, but the goal is not to use the new drug early," adding, "Using two mechanisms to maximize the total duration of disease control and waiting for clinical progression is the evidence-based standard."

He also said, "In less than 1 year after approval, Inluriyo has become a leading treatment option for ER+, HER2-, ESR1-mutated metastatic breast cancer, and more than half of patients currently starting an oral SERD are choosing it."

The oral SERD market is expanding into early breast cancer. Itacama and Roche’s giredestrant failed to meet the primary endpoint in phase 3 trials evaluating them as first-line treatments for advanced disease.

Giredestrant has produced positive phase 3 results as adjuvant therapy, but questions remain about the trial design because it did not include a CDK4/6 inhibitor. Lilly and AstraZeneca are also conducting phase 3 trials in early disease.

Adjuvant therapy is considered the largest market opportunity for oral SERDs. Van Naarden argued that tolerability could determine the ultimate winner in the adjuvant setting, where patients must take medication for 5 to 10 years.

He said, "Patients can benefit from a drug only if they take it."