LifeCodexx AG today announced the successful completion of the clinical validation study of its noninvasive test method for the detection of fetal trisomy 21 from maternal blood using Next Generation sequencing. First results from the prospective blinded multi-center study demonstrate highest clinical accuracy for the planned commercial PraenaTest® test design based on Cell-Free DNA™ blood collection tubes (BCT), detecting all positive cases of fetal trisomy 21 (100% sensitivity) with no false positive calls (100% specificity).
During the study, five prenatal centers and university hospitals in Germany and Switzerland recruited a total of 522 maternal blood samples from pregnant women with high risk of chromosomal alterations in the unborn child. Gestational age ranged from week 11+0 to 32+1. The main goal of the study was to compare detection rates for trisomy 21 of a test method based on Next Generation sequencing using maternal blood with conventional karyotyping using invasive methods, e.g. amniocentesis or chorionic villus sampling. For the study, maternal blood was sampled in two different ways, either using regular K3 EDTA blood collection tubes or Cell-Free DNA™ blood collection tubes (BCT). While for the K3 EDTA blood collection tubes the study centers had to prepare blood plasma at their sites before shipment, the use of Cell-Free DNA™ BCT required direct dispatch to LifeCodexx without any prior preparation work at the physician´s site.
First-cut analysis of the full set of recruited samples with 42 positive trisomy 21 cases showed an overall clinical sensitivity of 95% and specificity of 99.5%. However, a more detailed analysis revealed substantial differences between the blood sampling methods with regard to clinical sensitivity and specificity. The results of the blood samples which were stabilised in K3 EDTA blood collection tubes achieved a sensitivity rate of 81.8% and a specificity rate of 98.7% only. In contrast, blood sampling using Cell-Free DNA™ BCT yielded far better results with 100% clinical sensitivity and specificity. Cell-Free DNA™ blood collection tubes preserve cell-free DNA circulating in plasma, allowing sample collection and shipment at room temperature without any additional preparation work at the phycisians' site.
"These clinical results demonstrate clearly the importance of a reliable and easy sampling procedure which is mandatory for an accurate noninvasive testing method based on Next Generation Sequencing ," comments Dr. Wera Hofmann, Medical Director of LifeCodexx AG. "The results also validate our unique cost efficient 12-plex massively parallel sequencing method using Illumina HiSeq 2000 as well as our proprietary bioinformatic analysis technology. As a result, we are able to reliably quantify a possible overabundance of chromosome 21 relative to the amount of the other chromosomes."
"The results of the study are very encouraging, because they clearly show that the test allows a very reliable noninvasive diagnosis for trisomy 21 in high-risk pregnancies," comments PD Dr. Markus Stumm from the Berlin Center for Prenatal Diagnosis and Human Genetics. "The new test has the long-term potential to considerably reduce the number of procedure-related pregnancy losses induced by invasive diagnostic methods. It is a very interesting second-tier test, especially for women with an increased aneuploidy risk after first trimester screening."
"We are currently in the final stage of preparing the regulatory dossier for CE approval so that PraenaTest® will be soon launched as an In Vitro Diagnostic (IVD) product. We expect that the test will be available initially within Germany, Switzerland, Austria and Liechtenstein," says Dr. Michael Lutz, CEO of LifeCodexx.
LifeCodexx will present first results of the clinical study at a number of congresses over the coming weeks, e.g. at the „Tuebinger Praenataltage" end of April 2012, the congress of the DGPGM in Bonn in May, the European Society of Human Genetics (ESHG) in Nuernberg as well as the BGGF in Wuerzburg in June.