Agendia Aims To Reshape Breast Cancer Care With Predictive Genomic Tests

Agendia Inc.'s chief medical officer William Audeh believes the company's genomic tests will help shape the future of early breast cancer detection and care by offering clinicians biological insights to inform personalized treatment regimens.

According to Audeh, the company’s tests address two critical questions: What type of cancer is it, and what is the likelihood of recurrence?

Answers to those questions can help doctors match each patient to the right treatment at the right time to minimize under- and over-treatment and improve quality of life.

“We’re uncovering diversity that isn’t seen in routine pathology, and that diversity has clinical implications.”

The Irvine, CA and Amsterdam, Holland-based breast cancer-focused molecular diagnostics company currently markets two in vitro laboratory-developed genomic profiling tests – MammaPrint and BluePrint.

MammaPrint – targeted to women with early-stage (stage I, II, or IIIA) invasive breast cancer that is less than 5 cm and is either node-negative or has spread to 1 to 3 lymph nodes – analyzes 70 genes in breast cancer tissue that are most associated with risk of breast cancer recurrence, classifying cases as high- or low-risk. Low-risk patients on average have a 1.3% chance of recurrence while high-risk patients have an 11.7% chance of recurrence, Agendia says.

Further stratification of MammaPrint results identifies four risk subgroups, ultra‐low (UL), low, high 1, and high 2, with specific prognostic and predictive outcomes, according to the company.

BluePrint is an 80-gene signature to identify the molecular subtype of breast cancer – basal, luminal, or HER2 – revealing the underlying biology or driving forces behind the cancer’s growth, which assists doctors in making treatment decisions. 

"The most important aspect, which is why Agendia started really, is that genomic profiling can identify women who can avoid unnecessary chemotherapy," Audeh said. “We’re uncovering diversity that isn’t seen in routine pathology, and that diversity has clinical implications.”

Recent Study Findings

Audeh pointed to study results published in the July issue of the Journal of Clinical Oncology, which support MammaPrint’s use in determining which women will benefit from extended endocrine therapy.

The study was part of a larger trial called NSABP B-42 in which almost 4,000 postmenopausal women with hormone-receptor positive (HR+) early-stage breast cancer who had been disease-free for five years after taking hormone therapy were randomly chosen to either continue taking the extended endocrine therapy (EET) letrozole for five more years or take a placebo.

The results showed that EET slightly reduced recurrence incidence, but it was not clear which women would benefit most from the extra treatment.

To figure this out, the researchers looked at a subgroup of 1,866 women from the trial. They used MammaPrint to classify their tumors by risk of cancer recurrence, finding that only women with “low risk” tumors derived a significant benefit from taking letrozole for five more years. The ultra low and high-risk groups did not experience statistically significant EET benefit.

"While we know that clinical factors are associated with the risk of developing a late recurrence in estrogen receptor-positive (HR+) breast cancer, they do not indicate whether those late recurrences are preventable,” Audeh says in a company statement, asserting that “these data support the utility of MammaPrint in predicting which women have a risk of late recurrence which is preventable by extended endocrine therapy.”

Given that cancer treatments such as chemotherapy and hormone therapy are associated with serious side effects, carefully selecting treatments that are truly necessary can help give patients a higher quality of life and ultimately reduce health care costs. Conversely, undertreating women can lead to recurrence of breast cancer, including instances where the cancer becomes incurable.

Audeh notes, "There is an enormous cost to recurrence of breast cancer: There is a societal cost, there is a personal cost to the individual, and a great deal of health care costs.”

Data from Agendia's MINDACT trial, published in 2016 in the New England Journal of Medicine and sponsored by the European Organization for Research and Treatment of Cancer, show that MammaPrint low-risk patients can avoid chemotherapy without compromising clinical outcomes.

The trial, which enrolled 6,693 patients at 112 cancer centers across Europe, found that 46% of breast cancer patients who were being considered for chemotherapy but whose tumors were classified as “MammaPrint low risk” had excellent survival rates without chemotherapy.

Market Authorization And Reimbursement Pathways

In Europe, both MammaPrint and BluePrint received the CE mark in 2018, allowing cancer centers to run the tests in their own labs.

MammaPrint received US Food and Drug Administration clearance in 2007 for identifying likely-to-develop metastases within five years following surgery. The diagnostic test, offered via Agendia’s central laboratory, has been covered under Medicare since 2008.

In 2017, the test received a favorable final payment determination by the Centers for Medicare and Medicaid for a category 1 CPT code, with no out-of-pocket cost for patients, Agendia says. The assay is also reimbursed by most commercial plans in the US and Puerto Rico for all stage I and II breast cancer patients and for patients with up to three positive lymph nodes. The test costs $4,200 in the US and €2,675 in Europe.

In recent years, Agendia has also made great strides to get reimbursement for MammaPrint in Europe. In 2020, the test was approved by the German authority, Federal Joint Committee (G-BA), for reimbursement for all breast cancer patients.

Last year, the test was approved by the Dutch National Healthcare Institute for reimbursement to women over 50 with hormone-positive, HER2-negative breast cancer and 0-3 lymph nodes involved with clinical high risk in the Dutch National Health Insurance basic package.

In 2022, Agendia announced a multi-year partnership with San Diego-based DNA sequencing and array-based technologies company Illumina to advance its next-generation sequencing (NGS) versions of MammaPrint and BluePrint utilizing the Illumina MiSeq platform.

The advantage of the NGS versions of BluePrint and MammaPrint is that they can be conducted on-site at institutions and facilities that have sequencing capability. However, says Audeh, currently most genomic profiling assays are performed at Agendia's laboratory in Irvine, South California, using microarray analysis after a tissue sample is received from the hospital.

According to AlphaSense, the company has raised $182m in private funding to date.

Other players in the space include Exact Sciences with its Oncotype DX test, which analyzes the activity of 21 genes to predict the likelihood of breast cancer recurrence for people with early-stage, HR+, HER2-negative invasive breast cancer. The test provides a recurrence score between 0 to 100, which helps to predict the potential benefit of adding chemotherapy to hormone therapy.

Hologic subsidiary Biotheranostics markets the Breast Cancer Index, also for patients with early-stage, HR+, HER2-negative breast cancer. The test analyzes the expression of 11 genes in a tumor sample to provide BCI Prognostic and BCI Predictive results, the former indicating risk of late distant recurrence and the latter predicting the likelihood of benefit from extended endocrine therapy beyond five years.

Growth Plus Reports projects that the genomics in cancer care market, estimated at $3.42bn in 2022, will climb to $28.52 billion by 2031, growing at a compound average growth rate of 15.3%, while Nova One Advisor believes the market will see a CAGR of 16.2% and reach $85.63bn by 2033 after totaling some $19.08bn in 2023.