FDA Approves Verzenio® (abemaciclib) as the First and Only CDK4/6 Inhibitor for HR+/HER2- High-Risk Early Breast Cancer

October 13, 2021 /BioValleyBIOON/ --Eli Lilly(Eli Lilly) recently announced that the U.S. Food and Drug Administration (FDA) has approvedTargeted anticancer drug Verzenio (Chinese trade name: Weize®, generic name: abemaciclib tablets): in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) as adjuvant therapy for high-risk early-stage HR+/HER2- breast cancerBreast cancer（EBC）Adult patients. Specifically:Lymph node-positive, high risk of recurrence, viaFDAThe approved test method is indicated for HR+/HER2- EBC patients with a Ki-67 score ≥20%.Ki-67 is a marker of cell proliferation.

Notably,Verzenio is the first and only CDK4/6 inhibitor approved for the above patient population. Furthermore, in the treatment of HR+/HER2- EBC, Verzenio is the first in nearly two decadesFDAFirst Drug Approved to Be Added to Adjuvant Endocrine Therapy. Data from the phase 3 monarchE study show that, in patients with node-positive, high-risk HR+/HER2- EBC, compared with standard adjuvant endocrine therapy (ET),Verzenio in combination with ET demonstrated a statistically significant and clinically meaningful reduction in the risk of disease recurrence.

This FDA approval builds on the existing evidence for Verzenio, which was previously approved for the treatment of certain types of HR+/HER2- advanced or metastatic breast cancer. Along with this approval,FDAThe use of Verzenio has also been expanded across all indications to include male patients when used in combination with endocrine therapy (ET). Verzenio tablets are available in strengths of 200 mg, 150 mg, 100 mg, and 50 mg.

On March 8, 2021 (International Women's Day), Verzenio® was officially launched in China!

monarchE is a randomized (1:1), open-label, two-arm, multicenter Phase 3 trial enrolling adult male and female patients with HR+/HER2-, node-positive, resected early breast cancer (EBC) who exhibit clinical and pathological features consistent with a high risk of recurrence. In the trial, patients were randomized 1:1 into two groups: one group received Verzenio (150 mg twice daily) in combination with standard adjuvant ET, and the other group received standard adjuvant ET alone for a treatment duration of 2 years. Following the treatment period, all patients continued to receive ET for 5 to 10 years per physician discretion. The primary endpoint of the trial was invasive disease-free survival (IDFS).

The trial met the primary endpoint at the second interim analysis in the intent-to-treat (ITT) population:Compared with the ET treatment group, the Verzenio + ET treatment group demonstrated a statistically significant improvement in IDFS, with a 28.7% reduction in the risk of breast cancer recurrence (HR = 0.713; 95% CI: 0.583, 0.871; p = 0.0009).

After the primary endpoint was met in the ITT population, a prespecified IDFS analysis was conducted in patients with high-risk clinical and pathologic factors and a Ki-67 score ≥20%. This subgroup (n=2003) included patients with ≥4 positive axillary lymph nodes (ALNs), or 1–3 positive ALNs with grade 3 disease and/orTumor≥5 cm, Ki-67 score ≥20%. The results showed that,In this prespecified subgroup of patients, compared with the ET treatment group, the Verzenio + ET treatment group also demonstrated a statistically significant improvement in IDFS, with a 35.7% reduction in the risk of breast cancer recurrence (HR = 0.643; 95% CI: 0.475, 0.872; p = 0.0042).

This approval is based on the efficacy analysis results of the aforementioned subgroup, as well as post hoc additional follow-up. In this analysis, Verzenio combined with ET continued to demonstrate a clinically meaningful benefit: for patients with high-risk clinical and pathological features and a Ki-67 score ≥ 20%, Verzenio + ET reduced the risk of breast cancer recurrence or death by 37% compared with standard adjuvant ET (HR = 0.626; 95% CI: 0.49–0.80), with an absolute benefit of 7.1% in the 3-year IDFS event rate. In this analysis, the number of IDFS events was 104 in the Verzenio + ET group versus 158 in the ET group. Overall survival (OS) data remain immature, and further follow-up is ongoing. In this trial,# Adverse ReactionsConsistent with the known safety profile of Verzenio.

Sara M. Tolaney, MD, of Harvard Medical School and investigator on the monarchE trial, stated: "The design and results of the monarchE study are changing practice, representing the first advance in adjuvant therapy for HR+/HER2- breast cancer in a long time."FDA"The approval of Verzenio in combination with endocrine therapy for early breast cancer has the potential to become the new standard of care for this population. We are encouraged by the significant reduction in the risk of recurrence for these patients following a 2-year treatment period, and we are pleased to be able to offer this new treatment option to patients.”

Breast cancer is the most common cancer among women worldwide. It is estimated that 90% of breast cancers are diagnosed at an early stage.Diagnosis. Approximately 70% of breast cancers are HR+/HER2-, which is the most common subtype. Even within the HR+/HER2- subtype, breast cancer is a complex disease, and many factors—such as whether the cancer has spread to the lymph nodes,Tumorbiological characteristics—all will affect the risk of recurrence.

The active pharmaceutical ingredient of Verzenio is abemaciclib, an oral targeted CDK4/6 inhibitor that selectively inhibits cyclin-dependent kinases 4 and 6 (CDK4/6), restores cell cycle control, and blocksTumorCell proliferation. Cell cycle dysregulation is a hallmark of cancer, and CDK4/6 is overactive in many cancers, leading to uncontrolled cell proliferation. CDK4/6 are key regulators of the cell cycle that trigger the transition from the growth phase (G1 phase) to the DNA synthesis phase (S phase). In estrogen receptor-positive (ER+) breast cancer, CDK4/6 overactivity is highly prevalent, and CDK4/6 serves as a key downstream target of ER signaling. Preclinical data demonstrate that dual inhibition of CDK4/6 and ER signaling exhibits synergistic effects and can inhibit the growth of G1-phase ER+ breast cancer cells. Clinical evidence also indicates that abemaciclib crosses the blood-brain barrier. In patients with advanced cancer, including breast cancer, the concentrations of abemaciclib and its active metabolites (M2 and M20) in the cerebrospinal fluid are comparable to unbound plasma concentrations.

Verzenio was approved for marketing in October 2017 for the treatment of patients with HR+/HER2− advanced or metastatic breast cancer. The drug is indicated for: (1) in combination with an aromatase inhibitor (AI) as initial endocrine therapy for postmenopausal women; (2) in combination with fulvestrant for women with disease progression following endocrine therapy; (3) as monotherapy for adult patients with metastatic disease that progressed after prior endocrine therapy and chemotherapy.

Currently, several CDK4/6 inhibitors have been launched, in addition toEli LillyIn addition to Verzenio, there are alsoPfizerof Ibrance (palbociclib) andNovartisKisqali (ribociclib). In China, Pfizer's Ibrance (Chinese trade name: Aiboxin; generic name: palbociclib) was approved in August 2018, becoming the first CDK4/6 inhibitor approved in China. The indication for this drug is: in combination with an aromatase inhibitor, as initial endocrine therapy, for the treatment of postmenopausal women with HR+/HER2− locally advanced or metastatic breast cancer.

December 2020,Eli LillyVerzenio (Chinese Trade Name: Weize®, Generic Name: abemaciclib) Approved, becoming the second CDK4/6 inhibitor approved in China, indicated for the treatment of HR+/HER2- locally advanced or metastatic breast cancer: (1) in combination with an aromatase inhibitor as initial endocrine therapy for postmenopausal women; (2) in combination with fulvestrant for patients who have experienced disease progression following prior endocrine therapy.

March 8, 2021,Eli LillySimultaneous launch press conferences were held in Beijing and Shanghai: the CDK4/6 inhibitor Verzenio (WeiZe®, abemaciclib tablets) has been successfully launched in China. (Bioon.com)

Original Source:FDA Approves Verzenio® (abemaciclib) as the First and Only CDK4/6 Inhibitor for Certain People with HR+ HER2- High Risk Early Breast Cancer