Next-Generation Cologuard® Test Demonstrates High Sensitivity and Specificity in Pivotal BLUE-C Study, Significantly Outperforming Fecal Immunochemical Testing (FIT) for Cancer and Precancer Detection

American College of Gastroenterology (ACG) gives BLUE-C study late breaker status at 2023 annual meeting with presentation of the only head-to-head study results versus FIT at ACG

High specificity for next-generation Cologuard test expected to minimize unnecessary follow-up colonoscopies, supporting positive patient experiences¹

MADISON, Wis., Oct. 22, 2023 /PRNewswire/ -- Exact Sciences Corp. (NASDAQ: EXAS), a leading provider of cancer screening and diagnostic tests, today announced late-breaking data from the pivotal BLUE-C trial showing the next-generation Cologuard^® test met all study endpoints, demonstrating 94 percent sensitivity for colorectal cancer (CRC) at 91% specificity, during the American College of Gastroenterology (ACG) Annual Meeting 2023.^[1] Additionally, results show the next-generation Cologuard test was significantly more likely to detect cancer or precancer than fecal immunochemical testing (FIT)* (94% vs 67% and 43% vs 23%, respectively).^[1]  Finally, the next-generation Cologuard test demonstrated higher sensitivity for the most clinically significant form of advanced precancerous lesions (high-grade dysplasia at 75%) than FIT (47%).^[1]    

BLUE-C is one of the largest, most robust CRC screening trials ever conducted. It included more than 20,000 evaluable subjects in a population that aligns to the racial and ethnic diversity of the United States.^[1,2] Among these participants, the BLUE-C trial identified a total of 98 participants with colorectal cancer. Of these 82 (83.7%) had stage I to III cancers.^[1] 

"BLUE-C results demonstrate a new standard in non-invasive colorectal cancer and precancer detection, building on the strengths of current Cologuard," said Paul Limburg, MD, MPH, AGAF, chief medical officer, Screening, Exact Sciences. "The high sensitivity and specificity reported in BLUE-C will help drive improvement in patient experiences and will contribute to our quest to improve outcomes for this deadly cancer via accurate early detection."

Note: FIT positivity cut-off: hemoglobin >100 ng/mL. Colorectal cancer stages were defined per the American Joint Committee on Cancer Staging System, 8th ed.

BLUE-C Reports High Specificity

In addition to superiority over FIT in sensitivity for both colorectal cancer and advanced precancerous lesions, the next-generation Cologuard test demonstrated 91% specificity.¹ The specificity for FIT was 95%.^[1]

"Improving specificity of non-invasive stool-based screening tests while maintaining high sensitivity is a critical step in advancing the detection and prevention of colorectal cancer and minimizing the potential for unnecessary follow-up colonoscopies," said Thomas F. Imperiale, MD, Professor of Medicine at the Indiana University School of Medicine, research scientist at the Regenstrief Institute, and principal investigator for BLUE-C.

The 91% specificity reported in the BLUE-C trial for patients without advanced neoplasia is higher than the 87% specificity reported in Deep-C, the FDA registrational trial for Cologuard.^[1,3] For patients with a negative or non-neoplastic  findings on colonoscopy, specificity for the next-generation Cologuard test reached 93%. In this category, the specificity for FIT was 96%.^[1]  

Additional Analysis Presented at ACG Further Supports Performance of Next-Generation Cologuard

In addition to the BLUE-C pivotal data shared at ACG, Exact Sciences presented an analysis that describes a performance evaluation and validation of the next-generation Cologuard algorithm using a set of known test samples from the original Cologuard pivotal study (DeeP-C). In this additional analysis, all performance estimates of next-generation Cologuard performance were equivalent to or higher than the first-generation Cologuard test, confirming reproducibility and supporting clinically relevant performance of the next-generation Cologuard test.^[4]

"Promising data from the BLUE-C trial involving 20,000 patients is being presented at the American College of Gastroenterology," said Seth A. Gross, MD, professor of medicine, NYU Grossman School of Medicine. "The findings indicate that the next-generation mt-sDNA test demonstrates even higher sensitivity for colorectal cancer screening (94%) and high-grade dysplasia (75%), compared with the current Cologuard test.  These findings suggest that, if FDA approved, the mt-sDNA test will be a valuable option in providing non-invasive colorectal cancer screening." 

About the BLUE-C Study
BLUE-C was a multi-center, prospective study (NCT04144738) of more than 20,000 adults 40 years of age and older.^[1] The trial was designed to evaluate the performance of next-generation Cologuard (multi-target stool DNA or mt-sDNA). Using colonoscopy as a reference method, the robust study design compared next-generation Cologuard and a fecal immunochemical test (FIT^*). Blood samples were also collected for later evaluation of a blood-based screening test being developed by Exact Sciences. BLUE-C is one of the largest colorectal cancer screening trials ever conducted, and the study population reflects the racial and ethnic makeup of the United States according to the 2020 census.^[1,2]

About Next-Generation Cologuard
Developed in partnership with Mayo Clinic, the next-generation Cologuard test features novel biomarkers and improved laboratory processes. It also incorporates enhanced sample stability components to provide patients more time to return their sample to Exact Sciences' lab and increase the valid result rate.

In the coming months, Exact Sciences plans to release additional analyses of the BLUE-C data and complete its application to the FDA for approval of next-generation Cologuard.

About Cologuard

Cologuard revolutionized colorectal cancer screening by providing a convenient and accurate testing option for those at average risk. Nearly a decade later, Cologuard has been used to screen for colorectal cancer more than 12 million times.

Results from Exact Sciences' prospective, 90-site, point-in-time, 10,000-patient pivotal trial, DeeP-C, were published in the New England Journal of Medicine in March 2014. The Cologuard test is included in the American Cancer Society's (2018) colorectal cancer screening guidelines and the recommendations of the U.S. Preventive Services Task Force (2021) and National Comprehensive Cancer Network (2023). The Cologuard test is indicated to screen adults 45 years of age and older who are at average risk for colorectal cancer by detecting certain DNA markers and blood in the stool. Do not use the Cologuard test if you have had precancer, have inflammatory bowel disease and certain hereditary syndromes, or have a personal or family history of colorectal cancer. The Cologuard test is not a replacement for colonoscopy in high-risk patients. The Cologuard test performance in adults ages 45-49 is estimated based on a large clinical study of patients 50 and older. The Cologuard test performance in repeat testing has not been evaluated. 

The Cologuard test result should be interpreted with caution. A positive test result does not confirm the presence of cancer. Patients with a positive test result should be referred for colonoscopy. A negative test result does not confirm the absence of cancer. Patients with a negative test result should discuss with their doctor when they need to be tested again. Medicare and most major insurers cover the Cologuard test. For more information about the Cologuard test, visit cologuard.com. Rx only.

About Exact Sciences Corp.
A leading provider of cancer screening and diagnostic tests, Exact Sciences gives patients and health care professionals the clarity needed to take life-changing action earlier. Building on the success of the Cologuard^® and Oncotype^® tests, Exact Sciences is investing in its pipeline to develop innovative solutions for use before, during, and after a cancer diagnosis. For more information, visit ExactSciences.com, follow Exact Sciences on X (formerly known as Twitter) @ExactSciences, or find Exact Sciences on LinkedIn and Facebook.

NOTE: Exact Sciences and Cologuard are trademarks or registered trademarks of Exact Sciences Corporation. Oncotype is a registered trademark of Genomic Health, Inc., a wholly-owned subsidiary of Exact Sciences Corporation. All other trademarks and service marks are the property of their respective owners. 

Forward-Looking Statements
This news release contains forward-looking statements concerning our expectations, anticipations, intentions, beliefs, or strategies regarding the future. These forward-looking statements are based on assumptions that we have made as of the date hereof and are subject to known and unknown risks and uncertainties that could cause actual results, conditions and events to differ materially from those anticipated. Therefore, you should not place undue reliance on forward-looking statements. Examples of forward-looking statements include, among others, statements we make regarding the development and commercialization of the next-generation Cologuard test; the performance characteristics of next-generation Cologuard in a commercial setting; and the timing and anticipated results of additional analysis of the BLUE-C data and FDA submission. Risks and uncertainties that may affect our forward-looking statements are described in the Risk Factors sections of our most recent Annual Report on Form 10-K and any subsequent Quarterly Reports on Form 10-Q, and in our other reports filed with the Securities and Exchange Commission. We undertake no obligation to publicly update any forward-looking statement, whether written or oral, ®that may be made from time to time, whether as a result of new information, future developments or otherwise.

*The commercially-available Polymedco OC-Auto® Micro 80iFOB Test

References

1. Imperiale T, et al. Oral Presentation 54, ACG 2023.
2. United States Census Bureau. Annual Estimates of the Resident Population by Single Year of Age and Sex for the United States: April 1, 2020 to July 1, 2022 (NC-EST2022-AGESEX-RES). Accessed 16 October 2023. https://www.census.gov/data/tables/time-series/demo/popest/2020s-national-detail.html
3. Imperiale TF, et al. N Engl J Med. 2014;370(14):1287-1297.  
4. Imperiale T, et al. P0358, ACG 2023.

SOURCE EXACT SCIENCES CORP