Agendia recently presented new data on the predictive and prognostic abilities of its colorectal cancer and breast cancer assays that should help drive further adoption of these products in multiple diagnostics markets, company officials told Pharmacogenomics Reporter last week.
Agendia plans to launch ColoPrint — a genetic test that detects which colorectal cancer patients are most likely to benefit from adjuvant chemotherapy and whether they will remain disease-free for up to five years — under the CE Mark in Europe sometime later this year or early next year. As it did with its breast cancer recurrence assay MammaPrint, the company plans to seek approval from the US Food and Drug Administration for ColoPrint. It expects to submit the test to the FDA in 2010.
"We believe we have sufficient data to satisfy regulators and support ColoPrint's launch both in Europe and the US," Richard Bender, Agendia's chief medical officer, told Pharmacogenomics Reporter last week. Like MammaPrint, Agendia's colorectal cancer test is an in vitro diagnostic multivariate index assay, subject to FDA oversight.
"As with MammaPrint, we anticipate many independent validation studies to further underpin the robustness of ColoPrint and demonstrate its clinical utility and validity," Bender said.
Agendia presented an abstract last week at the American Society of Clinical Oncology's annual meeting in Orlando, Fla., reporting data from a validation study on the prognostic and predictive signature for ColoPrint.
Apart from this study, Agendia is in the process of conducting a large, international prospective trial further investigating the ColoPrint gene signature's ability to gauge disease recurrence in stage II colorectal cancer patients.
According to Bender, ColoPrint's platform is identical to MammaPrint, but the gene signature used to classify tissue samples is different. While MammaPrint uses a 70-gene profile, ColoPrint will utilize an 18-gene profile signature.
At the ASCO meeting, Agendia also presented several studies on the clinical validity, clinical utility, and cost-effectiveness of MammaPrint, which was the first IVDMIA to garner clearance from the FDA in 2007. However, when compared to the market success of Genomic Health's Oncotype DX test, Agendia's test has not been as widely adopted by oncologists in the US and many insurers have yet to reimburse for the test.
According to Bender, this is changing. In the coming months, the company plans to drive further coverage and adoption of MammaPrint on the strength of data from studies presented at ASCO.
ColoPrint Validation Study
The validation study on ColoPrint, by Glas et al., reported that "ColoPrint is able to predict the prognosis of stage II and III colon cancer patients and facilitate the identification of patients who would benefit from adjuvant chemotherapy."
The research team used Agilent 44K oligonucleotide arrays to analyze frozen tissue samples from 180 Stage I-III colorectal cancer patients undergoing surgery. Based on full-genome expression measurements, researchers from Agendia and various research institutions in the Netherlands classified patients into three molecular subclasses: A, B, and C.
Survival analysis showed that 27 patients in subclass C had poor outcome, while 48 patients in subclass A had good outcome. Researchers only used data from 104 subclass B patients (the intermediate group) to develop a gene signature associated with five-year distant metastasis free survival.
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The gene signature, comprising a set of 38 prognosis-related gene probes, was validated in an independent cohort of 178 tissue samples from patients with stage II and III colon cancer. In the study, patients were followed for almost six years and 85 percent of patients did not receive adjuvant chemotherapy.
According to the abstract, the profile classified 61 percent of validation samples as having a low risk of disease recurrence and 39 percent as having a high risk. "The low- and high-risk samples showed a significant difference in disease metastases-free survival with a hazard ratio of 3.19," the researcher reported.
At five years, approximately 90 percent of low-risk patients and just over 60 percent of high-risk patients had survived disease free.
"The performance of the profile was significant for both [adjuvant chemotherapy] untreated and treated patients, suggesting that its power [to detect disease recurrence] is independent of treatment benefits," the study authors said.
In addition to the study presented at ASCO, Agendia is also conducting the PARSC study — Prospective Study for the Assessment of Recurrence Risk in Stage II Colon Cancer Patients Using ColoPrint.
For this trial, Agendia has recruited 160 patients and aims to enroll 640 additional participants. Agendia said it is in discussions with US centers to recruit patients for this study. The first results from this study, with three-year follow-up of patients, is slated for release in 2012.
"The main objective of the study is to compare clinical risk assessment with ColoPrint and this can already reliably be achieved with the interim analysis," Bender said.
At ASCO, Agendia presented several abstracts further making the case for MammaPrint's clinical validity, clinical utility, and the cost-effectiveness of using the assay in the treatment of breast cancer.
In one study, by Bender et al., Agendia validated MammaPrint's ability to predict which patients with node-positive or node-negative breast cancer would respond to endocrine therapy and adjuvant chemotherapy regardless of estrogen receptor status. The company pooled MammaPrint outcomes for more than 1,600 patients and found that "patients with [a] poor prognosis MammaPrint profile had a substantial benefit from chemotherapy."
Particularly, at five years, distant disease-free survival was improved from 69 percent to 88 percent, when chemotherapy was added to hormone therapy. "The 70-gene MammaPrint profile is not only a strong and independent prognostic indicator for patients with early-stage breast cancer, but it may also be predictive for the benefit of chemotherapy," the researchers concluded in the abstract.
In another retrospective analysis, Agendia attempted to classify tumor samples from more than 500 women with ER-positive, HER2-negative, and lymph node-negative breast cancer, according to National Comprehensive Cancer Network's guidelines.
NCCN recommends molecular breast cancer profiling for ER-positive, HER2-negative, lymph node-negative disease. MammaPrint is indicated for the prognosis of lymph node-negative and positive breast cancer, independent of ER status.
In this study, by Snoo et al., Agendia reported that MammaPrint was "discordant with 62 percent of cases compared with NCCN guidelines" by identifying "66 percent of NCCN high-risk patients as having good prognosis."
As a result, the company suggests "integration of MammaPrint into clinical risk assessment and adjuvant treatment selection can provide a large benefit for management of patients with endocrine-responsive early breast cancer."
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Lastly, Agendia presented data from a study comparing the costs of using MammaPrint to decide treatment for women 61 years old or younger with lymph node-negative, HER2-negative, early-stage breast cancer with ER +/- disease versus making treatment decisions using traditional methods, with the so-called Adjuvant!Software.
"In this analysis, the 70-gene signature was associated with a reduction in chemotherapy use and an increase in life expectancy," researchers, Tong et al., concluded. "The 70-gene signature appears to be a cost-effective strategy for obtaining additional information to guide the decision to use adjuvant chemotherapy in patients with lymph-node negative, early-stage breast cancer."
According to the abstract, classifications made by MammaPrint resulted in 35 percent of patients being reassigned to different risk group than when these cases were analyzed by Adjuvant!Software. This spared approximately 10 percent of patients from receiving adjuvant chemotherapy.
"In the base case, the 70-gene signature strategy was cost neutral," resulting in lifetime costs per patient of $178,811 vs. $178,893 when analyzed by MammaPrint and Adjuvant!Software, respectively. Furthermore, treatment decisions made with guidance from MammaPrint increased 1.3 life years and 0.16 quality-adjusted life years.
Bender noted that this translates to an incremental cost-effectiveness ratio of $10,059 per life year and $9,428 per quality-adjusted life year. This is "well within the cost-effectiveness threshold value between $50,000 and $100,000 per QALY," Bender said.
Driving MammaPrint Adoption
On the strength of new data from these additional studies, "our main focus now is to … broaden the support of MammaPrint among medical practitioners," Bender said.
According to Bender, MammaPrint is currently being reimbursed by "several payors." The test is included in the policies of Blue Cross Blue Shield in several states, representing 10 percent of lives covered in the US.
"We are moving the process forward and get very positive feedback from our meetings with payors on the robustness of our data," Bender said. "Based on this feedback, we are optimistic that wider reimbursement is a matter of time."
Agendia had previously said that based on previous studies showing MammaPrint's ability to predict patients most likely to benefit from chemotherapy, it would seek an update from FDA on the assay's labeling. A predictive claim for MammaPrint would help it compete with Genomic Health's Oncotype DX, which is marketed as both a prognostic test for disease recurrence and a predictive test gauging chemotherapy benefit.
To date, there has been no head-to-head trial comparing the predictive and prognostic abilities of the two assays. "We would be very much in favor of a head-to-head study, but is a challenge given the two different technology platforms … that require different tissue preparation and so on," Bender said.
MammaPrint is a microarray-based test approved by the FDA for prognosticating disease recurrence for patients with node positive/negative, ER-positive/negative early stage breast cancer. RT-PCR-based Oncotype DX, meantime, is intended to be used by women with early-stage, node-negative, ER-positive invasive breast cancer who will be treated with hormone therapy.
Now, with the company's focus on driving adoption of the test, however, updating MammaPrint's FDA indication with a predictive claim "is not a priority," Bender noted.