Eli Lilly Drug Significantly Reduces the Risk of Breast Cancer Returning

Verzenio® (abemaciclib) Significantly Reduced the Risk of Cancer Returning in People with High Risk HR+, HER2- Early Breast Cancer

monarchE demonstrates positive results in Phase 3 study of 5,637 people whose early breast cancer is at a high risk of recurrence

 Verzenio given with standard endocrine therapy showed improvement compared to standard endocrine therapy alone

Verzenio is the only CDK4 & 6 inhibitor to demonstrate statistically significant improvement in invasive disease-free survival in this setting

 Lilly will submit data from monarchE to regulatory authorities around the world

INDIANAPOLIS -- Eli Lilly and Company (NYSE: LLY) today announced Verzenio® (abemaciclib) in combination with standard adjuvant endocrine therapy (ET) has met the primary endpoint of invasive disease-free survival (IDFS), significantly decreasing the risk of breast cancer recurrence or death compared to standard adjuvant ET alone. These results are from a pre-planned interim analysis of the Phase 3 monarchE study – making Verzenio the only CDK4 & 6 inhibitor to demonstrate a statistically significant reduction in the risk of cancer recurrence for people with high risk hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-) early breast cancer. The safety profile was consistent with that observed in other Verzenio studies in the MONARCH clinical program. Lilly plans to present these data at a medical meeting later this year.

"When a person is diagnosed with high risk early stage breast cancer, they strive to do everything in their power to prevent a recurrence. And as clinicians, we have the same goal," said Maura Dickler, M.D., vice president of oncology, late-phase development, Lilly Oncology. "monarchE was intentionally designed for people whose breast cancer is at a high risk of returning. We are incredibly excited by the results of monarchE and that we can potentially offer a new treatment option for patients with high risk HR+, HER2- early breast cancer. This would not have been possible without the tremendous commitment from the people who participated in this trial."

Despite progress in the treatment of breast cancer, approximately 30 percent of people diagnosed with HR+, HER2- early breast cancer are at risk of their cancer returning. This risk of recurrence increases based on certain clinical and/or pathological features such as breast cancer that has spread to the lymph nodes, a larger tumor size and a higher tumor grade. New treatment options are needed to advance the field and help prevent early breast cancer from returning, potentially to an incurable metastatic stage.

"We're proud that Verzenio has already treated tens of thousands of people around the world who are living with HR+, HER2- advanced breast cancer," said Anne White, President, Lilly Oncology. "And now Verzenio in combination with endocrine therapy has demonstrated positive results in people with high risk HR+, HER2- early breast cancer – a major milestone with the potential to change the paradigm of how early breast cancer is treated and a first for the CDK4 & 6 inhibitor class. The fact that these results were achieved early, at the interim analysis, is also exciting because it will help us speed this innovation to people who need it. We look forward to submitting these data to regulatory authorities before the end of 2020." 

The monarchE trial will continue through the completion date, estimated for June 2027. At the time of the interim analysis, the IDFS results are considered definitive. All patients on the monarchE trial will be followed until primary analysis and beyond to assess overall survival and other endpoints.

About the monarchE Study
monarchE is a Phase 3, multicenter, randomized, open-label trial that enrolled 5,637 patients with high risk, node positive, HR+, HER2- early breast cancer. Patients were randomized 1:1 to Verzenio (150 mg twice daily) plus standard adjuvant endocrine therapy or standard adjuvant endocrine therapy alone. Patients on the Verzenio arm receive treatment for up to two years or until discontinuation criteria are met. All patients receive standard endocrine therapy for at least 5 years if deemed medically appropriate. The primary objective is invasive disease-free survival, which in monarchE is defined as the length of time before any cancer comes back or death. Secondary objectives include distant relapse-free survival, overall survival, safety, pharmacokinetics and health outcomes.

High risk was specifically defined as women (any menopausal status) and men with resected HR+, HER2- invasive early breast cancer with either ≥4 pathologically positive axillary lymph nodes (pALNs) or 1 to 3 pathological pALNs with at least one of the following high-risk features: primary invasive tumor size ≥5 cm, histological grade 3 tumor, or central Ki-67 index ≥20%. If applicable, patients must have also completed adjuvant chemotherapy and radiotherapy prior to enrolling and have recovered from all acute side effects.

About Early Breast Cancer
Breast cancer is the most common cancer among women worldwide.1 An estimated 90 percent of all breast cancer is diagnosed at an early stage.2 Approximately 70 percent of all breast cancers are HR+, HER2-, the most common subtype.3 Even within this subtype, HR+, HER2- breast cancer is a complex disease, and many factors – such as if the cancer has spread to the lymph nodes and the biology of the tumor – can impact the risk of recurrence. Approximately 30 percent of people diagnosed with HR+, HER2- early breast cancer are at risk of their cancer returning, potentially to incurable metastatic disease.4

About Verzenio® (abemaciclib)
Verzenio (abemaciclib) is an inhibitor of cyclin-dependent kinases (CDK)4 & 6, which are activated by binding to D-cyclins. In estrogen receptor-positive (ER+) breast cancer cell lines, cyclin D1 and CDK4 & 6 promote phosphorylation of the retinoblastoma protein (Rb), cell cycle progression, and cell proliferation.

In vitro, continuous exposure to Verzenio inhibited Rb phosphorylation and blocked progression from G1 to S phase of the cell cycle, resulting in senescence and apoptosis (cell death). Preclinically, Verzenio dosed daily without interruption resulted in reduction of tumor size. Inhibiting CDK4 & 6 in healthy cells can result in side effects, some of which may be serious. Clinical evidence also suggests that Verzenio crosses the blood-brain barrier. In patients with advanced cancer, including breast cancer, concentrations of Verzenio and its active metabolites (M2 and M20) in cerebrospinal fluid are comparable to unbound plasma concentrations.

Verzenio is Lilly's first solid oral dosage form to be made using a faster, more efficient process known as continuous manufacturing. Continuous manufacturing is a new and advanced type of manufacturing within the pharmaceutical industry, and Lilly is one of the first companies to use this technology.

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Eli Lilly and Company

Lilly is a global healthcare leader that unites caring with discovery to create medicines that make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism.