Health Canada Authorizes Verzenio® (abemaciclib) as the First and Only CDK4/6 Inhibitor for patients with HR+ HER2- High Risk Early Breast Cancer

• Adding Verzenio to endocrine therapy demonstrated a significant and clinically meaningful reduction in the risk of recurrence in patients with hormone receptor positive (HR+) and human epidermal growth factor 2 negative (HER2-), node-positive, high risk early breast cancer and a Ki-67 score of ≥20%
• Verzenio was first authorized in Canada in 2019 for the treatment of estrogen and/or progesterone HR+ HER2-, metastatic breast cancer (mBC)

TORONTO, Jan. 27, 2022 /CNW/ - Lilly Canada is pleased to announce that Health Canada has authorized Verzenio^® (abemaciclib) (tablets), in combination with endocrine therapy, 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 and a Ki-67 score ≥20%. Ki-67 is a marker of cellular proliferation. Verzenio is the first and only CDK4/6 inhibitor approved for this patient population.  Verzenio was previously approved by Health Canada in August 2019 for metastatic breast cancer.

"This is an important approval for Canadian patients who are diagnosed with high-risk early-stage breast cancer," says Dr. Christine Brezden-Masley, Medical Director, Cancer Program at Sinai Health in Toronto. "We know that effectively treating cancer early provides the best opportunity for a long-term prognosis, and with compelling data showing a reduction in cancer recurrence after two years, this is a great new option for these patients."

"A breast cancer diagnosis is devastating. And when diagnosed in a young woman, it can be more aggressive and with a greater risk of recurrence. But regardless of the age or stage, what all breast cancer patients want is the path that will lead them to the best possible outcome," says MJ DeCoteau, Executive Director of Rethink Breast Cancer. "We're hopeful this new approval in the early setting will have an equally positive impact on patient outcomes as CDK4/6 inhibitors have had in the metastatic setting – which has truly been a game changer."

"Expanding options for Canadian patients with HR+ HER2- early breast cancer is incredibly important, especially when we know that treating aggressively early, can lead to positive patient outcomes later on," says Cathy Ammendolea, Chair of the Board of Directors for the Canadian Breast Cancer Network.  "This is great news for the breast cancer community in Canada."

The Verzenio Phase 3 monarchE trial was a randomized (1:1), open-label, multicentre 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. In the trial, patients were randomized to receive two years of Verzenio 150 mg twice daily plus physician's choice of standard endocrine therapy (ET), or standard ET 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. At the second interim efficacy analysis, with a median follow-up of 15.5 months, a statistically significant improvement in invasive disease–free survival (IDFS) was observed in patients who received Verzenio plus endocrine therapy versus those who received endocrine therapy alone. Patients treated with Verzenio plus endocrine therapy had a 25.3% reduction in risk of IDFS recurrence or death compared to patients treated with endocrine therapy alone. Consistent benefit was observed across patient stratification subgroups of geographic region, prior chemotherapy, and menopausal status.

At the final IDFS analysis, efficacy results were updated for the intent to treat (ITT) population, with a median follow-up of 19.1 months. Patients treated with Verzenio plus endocrine therapy had a 28.7% reduction in risk of recurrence or death compared to patients treated with ET alone (IDFS HR=0.713, 95% CI: 0.583, 0.871) and the 2-year IDFS rates were 92.3% and 89.3%, respectively. Also, patients treated with Verzenio plus ET had a 31.3% reduction in risk of distant recurrence or death compared to patients treated with ET alone [distant relapse free survival (DRFS) HR=0.687, 95% CI: 0.551, 0.858] and the 2 year DRFS rates were 93.8% and 90.8%, respectively. The most common sites of distance recurrence were bone, liver, and lung.  In this efficacy analysis, overall survival data were immature and a total of 106 patients had died (55 deaths (2.0%) in patients treated with Verzenio plus ET and 51 deaths (1.8%) with ET alone).²

Having achieved the study's primary endpoint in the entire enrolled population, a pre-specified analysis of IDFS was also conducted in patients with high-risk clinical and pathological factors and a Ki-67 score ≥20%. This subgroup analysis (N=2,003) included patients with ≥4 positive axillary lymph nodes (ALN), or 1-3 positive ALN with either Grade 3 disease and/or tumour size ≥5 cm, and whose tumours had a Ki-67 score of ≥20%. There was also a statistically significant improvement in IDFS for this pre-specified subgroup of patients receiving Verzenio plus ET compared to those who received ET alone (HR=0.643, 95% CI: 0.475, 0.872, p=0.0042).²

Adverse reactions from monarchE were consistent with the known safety profile for Verzenio.¹ Safety and tolerability were evaluated in 2,791 out of 5,591 patients who received at least one dose of study treatment.² The most common adverse reactions reported in ≥20% of patients in any study receiving abemaciclib in combination with endocrine treatment or as a single agent were diarrhea, neutropenia, fatigue, infections, nausea, vomiting, abdominal pain, decreased appetite, anemia, alopecia, leukopenia, headache, and thrombocytopenia.² 

This approval builds on the established body of evidence for Verzenio, which is already approved for the treatment of certain types of HR+ HER2- advanced or metastatic breast cancer in women.  Verzenio is available in tablet strengths of 200 mg, 150 mg, 100 mg, and 50 mg.

Data supporting this approval were presented at the September 2020 European Society for Medical Oncology (ESMO) Virtual Congress.

About the monarchE Study
The efficacy of Verzenio plus physician's choice of standard endocrine therapy was evaluated in monarchE, a randomized (1:1), open-label, multicenter study in adult women and men with HR-positive, HER2-negative, node-positive, resected, early breast cancer (EBC) with clinical and pathological features consistent with a high risk of disease recurrence. To be enrolled, all patients had to have HR positive, HER2-negative EBC with tumor involvement in at least 1 axillary lymph node (pALN). Two cohorts of patients were enrolled. To be enrolled in cohort 1, patients needed to have either ≥4 pALN, or pALN 1-3 and tumor grade 3 and/or tumor size ≥ 50 mm. To be enrolled in cohort 2, patients were required to have pALN 1-3 and Ki-67 score of ≥20% as measured in untreated breast tumor tissue, using a clinical trial assay at a central laboratory. For patients in cohort 1 with available untreated breast tissue samples, retrospective central testing of tissue was conducted to establish if the Ki-67 score was ≥20% or < 20% (specified in the protocol as "Ki-67 high" or "Ki-67 low", respectively). The intent to treat (ITT) population included patients from both cohort 1 (n=5120) and cohort 2 (n=517). Randomization to treatment was stratified by prior treatment (neoadjuvant chemotherapy versus adjuvant chemotherapy versus no chemotherapy); menopausal status (premenopausal versus postmenopausal); and region (North America/Europe versus Asia versus other). Men were stratified as postmenopausal.^1,2 

About Early Breast Cancer and Risk of Recurrence
It is estimated that 90 per cent of all breast cancers are detected at an early stage. 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 commonly diagnosed cancer worldwide, according to GLOBOCAN. The estimated 2.3 million new cases indicate that 1 in every 8 cancers diagnosed in 2020 is breast cancer. With approximately 685,000 deaths in 2020, breast cancer is the fifth-leading cause of cancer death worldwide.⁵ In Canada, 27,700 Canadian women were diagnosed with breast cancer, in 2021. It represents 13% of all cancer deaths in Canada. Breast cancer accounts for 25% of all new cancer cases in women in 2021.⁶ Approximately 70 per cent of all breast cancers are of the HR+ HER2- subtype.⁷

About Verzenio^® (abemaciclib)
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.

INDICATIONS FOR VERZENIO

Early Breast Cancer

Verzenio^® (abemaciclib) (tablets) is indicated in combination with endocrine therapy 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 and a Ki-67 score ≥20 per cent.

Advanced or Metastatic Breast Cancer

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.

About Lilly Canada
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.

For our perspective on issues in healthcare and innovation, follow us on twitter @LillyPadCA.  

Lilly Forward-Looking Statement 
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Verzenio (abemaciclib) as a treatment for patients with early breast cancer and reflects Lilly's current beliefs. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of development and commercialization. Among other things, there can be no guarantee that future study results will be consistent with the results to date or that Verzenio will receive additional regulatory approvals or be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly's most recent Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.

References

¹ Johnston SRD, Harbeck N, Hegg R, et al; monarchE Committee Members and Investigators. Abemaciclib combined with endocrine therapy for the adjuvant treatment of HR+, HER2-, node-positive, high-risk, early breast cancer (monarchE). J Clin Oncol. 2020;38(34):3987-3998. doi:10.1200/JCO.20.02514.
²  Verzenio product monograph
³ Early Breast Cancer Trialists' Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365(9472):1687-1717. doi:10.1016/S0140-6736(05)66544-0.
⁴ Cheng L, Swartz MD, Zhao H, et al. Hazard of recurrence among women after primary breast cancer treatment--a 10-year follow-up using data from SEER-Medicare. Cancer Epidemiol Biomarkers Prev. 2012;21:800-809.
⁵ Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-249
⁶ Canadian Cancer Society: Breast Cancer statistics – Last accessed, December 10, 2022.

⁷ National Cancer Institute, SEER. Cancer Stat Facts: Female Breast Cancer. https://seer.cancer.gov/statfacts/html/breast.html. Accessed September 14, 2021.

SOURCE Eli Lilly Canada Inc.

Ethan Pigott, Eli Lilly Canada, [email protected], [phone]; Laura Patton, Cohn & Wolfe, [email protected], [phone]