Home Active Pharmaceutical Ingredients (API)Abemaciclib Agilent Technologies’ Ki-67 IHC MIB-1 PharmDx assay has been approved by the FDA for use as a Companion Diagnostic to Eli Lilly’s Abemaciclib, or Verzenio.

Agilent Technologies’ Ki-67 IHC MIB-1 PharmDx assay has been approved by the FDA for use as a Companion Diagnostic to Eli Lilly’s Abemaciclib, or Verzenio.

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KEYPOINTS

  • The FDA has given the Ki-67 IHC MIB-1 pharmDx assay a companion diagnostic approval for detecting Ki-67 expression in patients with high-risk early breast cancer who are being considered for treatment with Abemaciclib.
  • The assay will be used to identify patients with early breast cancer who have an increased disease recurrence risk.
  • The first approval of an immunohistochemistry assay that measures Ki-67 expression in the context of treatment with Abemaciclib.
  • A companion diagnostic is a medical device, often an in vitro device, which provides information that is essential for the safe and effective use of a corresponding drug or biological product.
  • On 12 October 2021 FDA Approved Abemaciclib in Combination with Endocrine Therapy for Early Breast Cancer.
  • Verzenio®Abemaciclib is a targeted treatment known as a CDK4/6 inhibitor.
  • This is the first CDK 4/6 inhibitor approved for adjuvant treatment of breast cancer.
  • Antigen KI-67 also known as Ki-67 or MKI67 (Marker Of Proliferation Ki-67) is a protein that in humans is encoded by the MKI67 gene (antigen identified by monoclonal antibody Ki-67)
  • The Ki-67 percentage score is defined as the percentage of positively stained tumor cells among the total number of malignant cells assessed
  • IHC is used to show whether or not the cancer cells have HER2 receptors and/or hormone receptors on their surface.
  • Mib-1 proliferation index is an independent predictor of lymph node metastasis in invasive breast cancer
Agilent, Technologies, Ki67, IHC, MIB1, PharmDx, Assay, FDA, Approved, Companion, Diagnostic, American, Joint, Committee, Eli, Lilly's, Abemaciclib, Verzenio, Breast, Cancer, Adjuvant, treatment, Marker, Proliferation, Antigen, Percentage, Tumor, HER2, hormone, Receptors, Independent, Predictor, Lymph, Node

Agilent Technologies Inc. announced its Ki-67 IHC MIB-1 pharmDx (Dako Omnis) is now FDA approved.

Agilent Technologies Inc. announced its Ki-67 IHC MIB-1 pharmDx (Dako Omnis) is now FDA approved as an aid in identifying patients with early breast cancer (EBC) at high risk of disease recurrence, for whom adjuvant treatment with Verzenio (Abemaciclib) in combination with endocrine therapy is being considered. This is the first IHC assay measuring Ki-67 expression to receive FDA approval in the context of treatment with Verzenio and was developed in collaboration with Eli Lilly and Company.

Experts expressed that understanding the risk of recurrence present in patients with early breast cancer is imperative in informing disease management and identifying those who are at high risk to inform treatment decisions and improve outcomes. Current methods for determining the risk of recurrence in this patient population are based on staging and are performed according to standard clinical and

The American Joint Committee on Cancer has identified the Ki-67 biomarker as Level of Evidence III in diagnosing EBC due to its association with cellular proliferation. Ki-67 is thus an important component of comprehensive risk assessment, but it has been inconsistently applied in the past.1

“Agilent’s Ki-67 IHC MIB-1 pharmDx (Dako Omnis) companion diagnostic assay for the Dako Omnis advanced staining platform has been designed and tested to aid in evaluating the risk of recurrence in early breast cancer (EBC),” said Sam Raha, president of Agilent’s Diagnostics and Genomics Group. “Its approval establishes a clinically relevant standard for recurrence risk assessment in EBC so that more high-risk patients who may experience clinical benefit from treatment with Verzenio are identified.”

This approval builds on Agilent’s previous successes in expanding the clinical applicability of therapeutic biomarker analysis, further cementing the company’s position as a provider of diagnostic assays that deliver high quality and ease of implementation.

Abemaciclib with endocrine therapy for early breast cancer.

the Food and Drug Administration approved Abemaciclib (Verzenio, Eli Lilly and Company) with endocrine therapy (tamoxifen or an aromatase inhibitor) for 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 recurrence and a Ki-67 score ≥20%, as determined by an FDA approved test. This is the first CDK 4/6 inhibitor approved for adjuvant treatment of breast cancer.

Approval of the Abemaciclib combination for this indication was based on data from the phase 3 monarchE trial (NCT03155997), a randomized. open-label, 2-cohort, multicenter study of approximately 5637 patients.

What is 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 the S phase of the cell cycle, resulting in senescence and apoptosis (cell death). Preclinically, Verzenio dosed daily without interruption resulted in a 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.

About the monarchE Study

monarchE is a global, randomized, open-label, two cohort, multicentre 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 tumor 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). Secondary endpoints were IDFS in patients with high Ki-67 scores (in the ITT population and in the Cohort 1 population), DRFS, overall survival, and safety.

About Early Breast Cancer and Risk of Recurrence

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

Node-positive means that cancer cells from the tumor in the breast have been found in the lymph nodes in the armpit area. Although breast cancer is removed through surgery, the presence of cancer cells in the lymph nodes signifies that there is a higher chance of 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 in breast cancer. With approximately 685,000 deaths in 2020, breast cancer is the fifth-leading cause of cancer death worldwide.6 In the U.S., it is estimated that there will be 281,550 new cases of breast cancer in 2021.7

Approximately 70 percent of all breast cancers are of the HR+ HER2- subtype.7

What is 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 the S phase of the cell cycle, resulting in senescence and apoptosis (cell death). Preclinically, Verzenio dosed daily without interruption resulted in a 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.

What is a companion diagnostic?

A companion diagnostic is a medical device, often an in vitro device, which provides information that is essential for the safe and effective use of a corresponding drug or biological product. The test helps a health care professional determine whether a particular therapeutic product’s benefits to patients will outweigh any potentially serious side effects or risks.

Companion diagnostics can:

-identify patients who are most likely to benefit from a particular therapeutic product;

-identify patients likely to be at increased risk for serious side effects as a result of treatment with a particular therapeutic product; or

-monitor response to treatment with a particular therapeutic product for the purpose of adjusting treatment to achieve improved safety or effectiveness.

What is ki-67?

Antigen KI-67 also known as Ki-67 or MKI67 (Marker of Proliferation Ki-67) is a protein that in humans is encoded by the MKI67 gene (antigen identified by monoclonal antibody Ki-67)

Antigen KI-67 is a nuclear protein that is associated with cellular proliferation. Altering Ki-67 expression levels did not significantly affect cell proliferation in vivo. Ki-67 mutant mice developed normally and cells lacking Ki-67 proliferated efficiently. Furthermore, it is associated with ribosomal RNA transcription. Inactivation of antigen KI-67 leads to inhibition of ribosomal RNA synthesis.

What is considered a high Ki67 score?

A result of less than 6% is considered low, 6-10% intermediate, and more than 10% is considered high. Ki-67: Ki-67 is a protein in cells that increases as they prepare to divide into new cells. A staining process can measure the percentage of tumor cells that are positive for Ki-67

IHC Tests

IHC, or ImmunoHistoChemistry, is a special staining process performed on fresh or frozen breast cancer tissue removed during a biopsy. IHC is used to show whether or not the cancer cells have HER2 receptors and/or hormone receptors on their surface. This information plays a critical role in treatment planning.

What does IHC positive mean?

A positive test result means that the laboratory found a particular change in the proteins of your tumor. This means that it is possible that you have an inherited genetic condition and further genetic testing is recommended.

What does IHC mean in cancer?

Immunohistochemistry (IHC) is an important application of monoclonal as well as polyclonal antibodies to determine the tissue distribution of an antigen of interest in health and disease. IHC is widely used for the diagnosis of cancers; specific tumor antigens are expressed de novo or up-regulated in certain cancers.

MIB-1 index.

The MIB-1 labeling index was defined as the percentage of immunoreactive tumor cells in the evaluated area.

About Agilent technologies.

Agilent Technologies, Inc. is an American analytical instrumentation development and manufacturing company that offers its products and services to markets worldwide. Its global headquarters is located in Santa Clara, California. Agilent was established in 1999 as a spin-off from Hewlett-Packard. The resulting IPO of Agilent stock was the largest in the history of Silicon Valley at the time.

The company provides analytical instruments, software, services, and consumables for the entire laboratory workflow. Agilent focuses its products and services on six markets: food, environmental and forensics, pharmaceutical, diagnostics, chemical and energy, and research. From 1999 to 2014, the company also produced test and measurement equipment for electronics; that division was spun off to form Keysight.

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