LILLY ANNOUNCES HEALTH CANADA'S AUTHORIZATION OF VERZENIO® (ABEMACICLIB) LABEL EXPANSION

• Verzenio's label expanded to include the full study population investigated in the Verzenio Phase 3 monarchE trial.
• Approval supported by four-year data from the monarchE trial; Verzenio added to adjuvant endocrine therapy (ET) reduced the risk of recurrence by 34% compared to adjuvant ET alone.
• Verzenio remains the first and only CDK4/6 inhibitor approved in the adjuvant setting.

TORONTO, Dec. 7, 2023 /CNW/ - Eli Lilly Canada Inc. is pleased to announce that Health Canada has authorized the label expansion of Verzenio® (abemaciclib) to include the full intention to treat (ITT) population from the Phase 3 monarchE trial. Verzenio is now indicated in combination with endocrine therapy (ET) for the adjuvant treatment of adult patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), node-positive, early breast cancer (EBC) at high risk of recurrence based on clinicopathological features, as defined by the presence of four or more positive nodes, or one to three positive nodes and at least one of the following: a tumour of ?5 cm, histological grade 3 disease, or Ki-67 score ?20%. This represents a broader population of patients than what was initially approved by Health Canada for EBC in 2022.

"Twenty per cent of patients diagnosed with HR positive, HER2 negative early breast cancer will experience recurrence, potentially to incurable metastatic disease," said MJ DeCoteau, Founder and Executive Director at Rethink Breast Cancer. "This expanded indication not only broadens treatment possibilities for more patients, it also underscores the importance of tailored solutions that put the power back into the hands of those who choose to tackle their diagnosis as aggressively as possible."

"The expanded indication for Verzenio will allow a wider population of women with high risk early breast cancer to be eligible for this treatment, which is a major step forward in personalizing therapy and improving patient care," said Dr. Karen Gelmon, Professor of Medicine, UBC. "It's an exciting time in the field of oncology as we continue to make strides in improving patient outcomes."

"For Canadians diagnosed with early breast cancer, the fear of recurrence is very real and adds stress to an already uncertain time in their lives," said Cathy Ammendolea, Chair of the Board of Directors at the Canadian Breast Cancer Network. "We are so pleased that, through this label expansion, more patients will have access to this therapy, providing additional hope and improved outcomes for even more patients diagnosed with early breast cancer."

This label expansion is supported by four-year follow up data from the Phase 3 monarchE trial which compared the use of 2 years of adjuvant Verzenio in combination with ET vs ET alone in HR+, HER2- node-positive EBC patients at high risk of recurrence based on clinicopathological features. The four-year follow up data indicates that adjuvant Verzenio reduces the risk of disease recurrence and that Verzenio's benefit is sustained beyond the completion of treatment. At four years, 85.8% of patients remained recurrence-free with Verzenio plus ET, compared to 79.4% of patients treated with ET alone, an absolute difference in Invasive Disease-Free Survival (IDFS) of 6.4%. Verzenio + ET treatment led to a 34% relative risk reduction in IDFS compared to ET alone (HR=0.664 [95% CI: 0.578-0.762]). At the four-year time point, the magnitude of benefit in Distant Relapse-Free Survival (DRFS) also deepened beyond treatment completion. Within the population on adjuvant Verzenio plus ET, 88.4% did not experience a distant recurrence, compared to 82.5% of patients within the ET alone arm, an absolute difference of 5.9%. The addition of abemaciclib plus ET resulted in a 34% reduction in the risk of metastatic recurrence, compared to ET alone (HR=0.659 [95% Cl: 0.567, 0.767]). No new safety findings were identified and overall results are consistent with the well-established safety profile for Verzenio.

"Verzenio's expanded label provides a preventative treatment option for a greater number of men and women in Canada who have faced an HR-positive, HER2-negative early breast cancer diagnosis, with high risk of recurrence," said Dr. Kenneth Custer, General Manager of Lilly Canada. "I am beyond pleased that Canada is a standout in ensuring early breast cancer patients will now have access to this important therapy to the fullest extent of the population investigated in our clinical trials."

The monarchE study enrolled 5,637 adults with high-risk HR+, HER2-, node-positive EBC. Verzenio is now approved for use in the full ITT patient population.  The "About the monarchE Study" section below provides more details on study design.

Adverse reactions from monarchE were consistent with the known safety profile for Verzenio.¹ Safety and tolerability were evaluated in 5,591 patients. The most common adverse reactions reported (>10%) in the Verzenio plus ET (tamoxifen or an aromatase inhibitor) arm, and >2% higher than the ET arm alone, were diarrhea, infections, fatigue, nausea, headache, vomiting, stomatitis, decreased appetite, dizziness, rash, and alopecia.² The most common laboratory abnormalities (all grades ?10%) were increased creatinine levels, decreased white blood cell count , decreased neutrophil count, anemia, decreased lymphocyte count , decreased platelet count, increased ALT, increased AST, and hypokalemia.

To view the full Verzenio product monograph, please visit lilly.ca.

About the monarchE Study monarchE was a global, randomized, open-label, multicenter Phase 3 study in adult women and men with HR+ HER2-, node-positive resected EBC with clinical and pathological features consistent with a high risk of disease recurrence. A total of 5,637 patients were randomized (1:1) to receive two years of Verzenio 150 mg twice daily plus physician's choice of standard endocrine therapy, or standard endocrine therapy alone. Patients in both treatment arms were instructed to continue to receive adjuvant endocrine therapy for up to 5-10 years as recommended by their clinician. Cohort 1 enrolled patients with ?4 positive axillary lymph nodes (ALN), or 1-3 positive ALN and either Grade 3 disease or tumour size ?5 cm. Cohort 2 enrolled patients with 1-3 positive ALN and centrally determined Ki-67 score of ?20%. The primary endpoint was IDFS in the ITT population (Cohorts 1 & 2).

About Early Breast Cancer and Risk of Recurrence It is estimated that 90 percent of all breast cancers are detected at an early stage. Approximately 70 per cent of all breast cancers are of the HR+ HER2- subtype. Although the prognosis for HR+ HER2- EBC is generally positive, 20 per cent of patients will experience recurrence potentially to incurable metastatic disease.³ Risk of recurrence is greatest within the initial two to three years post-diagnosis, particularly in patients with node-positive, high risk EBC.⁴ Factors associated with high risk of recurrence include: positive nodal status, large tumour size (?5 cm), high tumour grade (Grade 3), and high rate of cellular proliferation [Ki-67 score (?20%)].²

Node-positive means that cancer cells from the tumour in the breast have been found in the lymph nodes in the armpit area. Although the breast cancer is removed through surgery, the presence of cancer cells in the lymph nodes signifies that there is a higher chance of the cancer returning and spreading.

About Breast Cancer Breast cancer has now surpassed lung cancer as the most diagnosed cancer worldwide, according to GLOBOCAN. In the report, breast cancer had an age standardized rate (ASR) of 82.1 per 100,000, which means that about 1 in every 8 of new Canadian cancer diagnosis in 2020 was breast cancer. With approximately 685,000 deaths in 2020, breast cancer is the fifth-leading cause of cancer death worldwide.⁵ In Canada, it is estimated that 29,400 Canadian women will have been diagnosed with breast cancer, by the end of 2023.⁶ This represents 26% of all new cancer cases in women in 2023.⁷

Verzenio^® abemaciclib is a targeted treatment known as a CDK4/6 inhibitor. Verzenio is a non-chemotherapy oral tablet.

Verzenio works inside the cell to block CDK4/6 activity and help stop the growth of cancer cells, so they may eventually die (based on preclinical studies). Cyclin-dependent kinases (CDK)4/6 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 tumour 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.

Verzenio^® (abemaciclib) (tablets) in combination with endocrine therapy (ET) is indicated for the adjuvant treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of disease recurrence based on clinicopathological features.

VERZENIO (abemaciclib) (tablets) is indicated for the treatment of hormone receptor (HR)- positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer.

• in combination with an aromatase inhibitor in postmenopausal women as initial endocrine based therapy.
• in combination with fulvestrant in women with disease progression following endocrine therapy. Pre- or perimenopausal women must also be treated with a gonadotropin-releasing hormone (GnRH) agonist.
• as a single agent in women with disease progression following endocrine therapy and at least 2 prior chemotherapy regimens. At least one chemotherapy regimen should have been administered in the metastatic setting, and at least one should have contained a taxane.

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

Eli Lilly Canada was established in 1938, the result of a research collaboration with scientists at the University of Toronto which eventually produced the world's first commercially available insulin. Our work focuses on oncology, diabetes, autoimmunity, neurodegeneration, and pain. To learn more about Lilly Canada, please visit us at www.lilly.ca.

SOURCE Eli Lilly Canada Inc.