Sequenom Announces New Positive Data on Down Syndrome Detection and Unveils Breakthrough DNA Approach to Prenatal Diagnostics
February 9th, 2009
2009 FEB 9 -- Sequenom, Inc. (NASDAQ:SQNM) announced new positive data from the prospective clinical studies using the Company’s noninvasive SEQureDx™ technology, enabling the detection of fetal aneuploidy from maternal blood. The data presented today consist of 459 new, high prevalence samples from the prospective, blinded studies performed at Sequenom, bringing the total number of samples studied to 858. Based on the results from the total study samples, including samples as early as 8 weeks of pregnancy, the Sequenom SEQureDx RNA-based technology demonstrated a 100% positive predictive value (PPV) and a 99.9% negative predictive value (NPV). The SEQureDx technology achieved a better than 99% detection rate, with less than a 1% false positive rate. The current standard of care, screening tests, perform at less than a 99% detection rate; however, statistically, if these screening tests could perform at a 99% detection rate, their false positive rate would be in the 10% to 25% range. SEQureDx compares favorably to the current invasive procedures, such as amniocentesis.
In addition to data on the RNA-based technology, the Company unveiled a breakthrough technology which further enhances Sequenom’s SEQureDx technology. This new DNA approach has demonstrated in early studies universal ethnic coverage, high sensitivity and specificity, and the ability to detect Trisomy 21 (Down syndrome), Trisomy 18 (Edwards syndrome) and Trisomy 13 (Patau syndrome) in a single test. This technology is being developed as a “reflex test” for unresolved results from the current SEQureDx Trisomy 21 technology will be available at the time of the launch of the Trisomy 21 laboratory developed test (LDT) in June 2009.
“We are very pleased with the completion of the R&D studies for our Trisomy 21 RNA-based technology,” stated Harry Stylli, Ph.D., President and Chief Executive Officer of Sequenom. “Our highly sensitive and specific Down syndrome technology will be transferred to the Sequenom Center for Molecular Medicine (SCMM) to complete the development and validation phases necessary for launch in June as an LDT. Our pioneering DNA approach is proving to be a powerful approach to detecting a wide range of aneuploidies. We are very excited by these early findings and believe it will play a key role in our prenatal diagnostics franchise as it eliminates unresolved results due to ethnic coverage and has shown sensitivity as early as eight weeks, similar to the current RNA approach. Furthermore, we believe it will have broad applicability in other areas such as cancer aneuploidies and other genetic disorders. This new approach and other approaches being developed by the Company are covered by existing and recently filed patents.” Overview of Data from Screening Studies Evaluating RNA-based Trisomy 21 Technology Elizabeth Dragon, Ph.D., Senior Vice President of Research and Development at Sequenom, presented data from blinded studies performed at Sequenom involving 459 new, high prevalence clinical samples collected prospectively, which brings the total number of samples studied to 858. The data from the 459 new samples show that Sequenom’s proprietary technology for Down syndrome correctly identified all eight first trimester Down syndrome samples (i.e. sensitivity or detection rate) with no false positives and no false negatives, as confirmed by chorionic villus sampling (CVS). Of the 15 second trimester confirmed Down syndrome samples, the Sequenom RNA-based technology detected 14 samples, with one unresolved result reflexed to the new DNA-based method. The DNA-based method accurately detected the Down syndrome. There was one false positive in the second trimester samples, which would be reflexed for confirmatory genetic testing per American College of Obstetricians and Gynecologists (ACOG) guidelines.
“These results represent a significant advance in noninvasive prenatal screening,” stated Allan T. Bombard, M.D., Chief Medical Officer of Sequenom. “In light of these outstanding results, the SEQureDx RNA-based Trisomy 21 technology clearly represents a paradigm-shifting approach. I am encouraged by the single false-positive result in this study representing one tenth of one percent of the total samples tested to-date, and the detection rate is notably superior to the current standard of care, biochemical screening tests. As an ob-gyn, I am confident the simplicity of the SEQureDx approach will be invaluable to physicians and the patients they care for and will result in substantially fewer invasive procedures." Breakthrough DNA Approach to Detection of Trisomy 21 and Other Aneuploidies In addition, Dennis Lo, M.D. Ph.D., Li Ka Shing Professor of Medicine at The Chinese University of Hong Kong, presented insights in future opportunities for noninvasive prenatal diagnostics, including pioneering work in a novel DNA approach to the detection of fetal aneuploidy, an approach which Sequenom is already evaluating in R&D studies.
Dr. Dragon from Sequenom presented early findings regarding this promising technology from 359 samples. These findings showed that the DNA-based method correctly identified all 68 unresolved results reflexed from the RNA method, including one confirmed positive Trisomy 21 sample. In addition, this method correctly identified four confirmed positive Trisomy 13 samples and four confirmed positive Trisomy 18 samples.
“We believe this technology represents a breakthrough approach for detecting chromosomal aneuploidies,” stated Dr. Dragon. “This method provides a universal method for detecting all chromosomal aneuploidies. The simple integration into RNA lab workflow of this MassARRAY-based technology does not impact timelines or costs. We will continue to evaluate this technology in parallel to the RNA method and plan to incorporate the DNA-based method into our launch plans.” Future Applications in Detection of Monogenic Diseases During his presentation, Dr. Lo focused on the future potential for Sequenom’s technology to address the unmet needs in detection of monogenic diseases. Currently, monogenic diseases, such as cystic fibrosis, B-thalassemia and sickle cell anemia, can only be definitively diagnosed prenatally through invasive procedures following extensive carrier screening testing on both parents. In the United States, cystic fibrosis screening is recommended for all women of child bearing age (more than 10 million individuals in the U.S. are carriers of the CF mutated gene, including one in every 29 Caucasian Americans) and in certain regions of the world, B-thalassemia affects anywhere from three to 16 percent of the population.
Data presented by Dr. Lo demonstrate that when individual mutant or normal DNA sequences are counted in maternal plasma using digital PCR technology, the number of mutant genes inherited by an unborn fetus, and hence its disease status, can be determined. He further demonstrated that a 'molecular counting' strategy can be made more efficient by taking into account the length of the DNA molecules in maternal plasma, as fetal DNA molecules are known to typically be shorter than the maternally derived molecules in maternal plasma. This digital counting approach enables the noninvasive diagnosis of B-thalassemia and hemoglobin E disease from maternal plasma—forms of inherited anemias that affect millions of people worldwide. This molecular counting strategy can, in principle, be applicable to all forms of monogenic diseases, namely paternally or maternally inherited, autosomal dominant diseases and autosomal recessive diseases with any combination of parental mutations. Thus, the complete diagnosis of monogenic diseases can be achieved noninvasively. Sequenom holds exclusive rights to this breakthrough technology representing a new approach that could potentially eliminate the need for paternal testing and significantly reduce the use of invasive tests.
"This new diagnostic approach addresses a problem that has been puzzling investigators in the field of noninvasive prenatal diagnostics over the last 10 years," stated Dr. Lo, study co-author. "Digital PCR technologies have enabled us to measure the minute imbalance of mutant and normal DNA sequences in maternal plasma. This has freed us from the past restriction for monogenic disease analysis where we could only look at the paternally-inherited mutations noninvasively. This research represents a significant paradigm shift in the way we approach plasma DNA-based diagnostics, and offers substantial promise for bringing noninvasive prenatal diagnosis of monogenic diseases closer to reality."
"Sequenom is committed to developing the next generation of prenatal diagnostic tools that will provide physicians with the capabilities they need to noninvasively diagnose genetic disorders early in a woman's pregnancy," commented Dr. Stylli. "We believe these unique, noninvasive digital technologies have the potential to dramatically impact the prenatal diagnostic market and we look forward to advancing these innovative approaches as part of our long-term strategy to expand our prenatal diagnostics franchise."
