As LifeCodexx is preparing the launch of its non-invasive prenatal trisomy 21 test in German-speaking countries this summer, the company is already thinking about expanding the test to additional indications in the future.
Last month, LifeCodexx, a subsidiary of German genomics service provider GATC Biotech, said that it had completed a clinical validation study for its PrenaTest. The study involved 522 samples from five prenatal centers and university hospitals in Germany and Switzerland (CSN 5/2/2012).
LifeCodexx, which is based in Constance in the South of Germany near the Swiss border, licenses intellectual property surrounding the test from Sequenom (CSN 8/17/2011), which launched a similar test in the US last year. Both tests run on the Illumina HiSeq 2000 platform, but while Sequenom currently multiplexes four samples per run, with plans to increase multiplexing, LifeCodexx will analyze 12 samples per run.
According to Wera Hofmann, LifeCodexx's medical director, the test method used by both companies — both essentially measure an overabundance of chromosome 21 DNA in maternal blood — is "very similar," and the companies' scientists collaborate. LifeCodexx's method differs mainly in the bioinformatics algorithm used to analyze the data. Following its pilot study, the company developed a new algorithm for its clinical validation study that uses a flow-cell-based set of reference samples, she said.
LifeCodexx is currently waiting for CE marking of the test from a German notified body, as required by the in vitro diagnostic medical devices directive of the European Union, which will allow it to launch PrenaTest as an in vitro diagnostic product. The company hopes to obtain the CE mark in June and launch the test shortly afterwards, according to Hofmann.
PrenaTest will initially be available in Germany, Switzerland, Austria, and Liechtenstein for women with high-risk pregnancies as determined by age, family history of trisomy 21, or a suspicious result in first trimester screening.
LifeCodexx validated its test method on a cohort of women with high-risk pregnancies. Offering it for low-risk pregnancies will require another validation study, which Hofmann said the company plans to initiate this year.
In addition, it is working on expanding its test later this year to the detection of trisomies 13 and 18 — a step Sequenom has already taken — which might require separate CE marking, she said.
The company will first offer the test through its clinical study partners. Its website also names 19 prenatal centers and practices — 18 in Germany and one in Switzerland — that plan to offer the test, a list that will likely expand over the next several weeks, according to Hofmann.
PraenaTest will cost €1,250 ($1,600), or 1,500 Swiss Francs ($1,600) in Switzerland, an out-of-pocket expense. Hofmann said that LifeCodexx is currently not talking with health insurance companies about reimbursement and declined to comment on the chances of obtaining reimbursement for the test in the future.
LifeCodexx's clinical validation study, which included 522 pregnant women with a high risk of fetal chromosomal alterations, showed that the test has a sensitivity and specificity of 100 percent when using a blood collection method that allowed doctors to ship blood samples at room temperature and without further preparation.
The use of the so-called Cell-Free DNA blood collection tubes, which preserve cell-free circulating DNA in plasma, made a significant difference to the results: when doctors used regular K3 EDTA blood collection tubes, which required them to prepare blood plasma at their own sites before shipment, the sensitivity of the test was only 81.8 percent and the specificity 98.7 percent.
The tubes are manufactured and sold by Streck Innovations, a company based in Omaha, Neb., and LifeCodexx currently has to order them directly from the US.
LifeCodexx is presenting the results of the study at several conferences this month and next. In collaboration with its clinical partners, it is currently writing a manuscript for publication in a peer-reviewed journal, according to Hofmann.
In its recently published Prenatal Diagnosis study, the company confirmed that it is able to detect trisomy 21 from maternal blood using next-generation sequencing reliably, essentially replicating results from Dennis Lo's group at the Chinese University of Hong Kong and from Sequenom.
In the same paper, LifeCodexx explored a targeted sequencing approach, using Agilent's SureSelect in-solution enrichment, to identify trisomy 13 and trisomy 21.
While the company is currently focused on the clinical validation of its PrenaTest, it is still pursuing targeted resequencing as a research project, Hofmann said. This would enable it not only to test for trisomies 21 and 13 but potentially to provide "full karyotyping," she said, which would also include, for example, different types of microdeletions.
LifeCodexx is also still working on a next-gen sequencing-based preeclampsia test, which is still in the research phase, Hofmann said. The company said last year that it was considering the PacBio RS platform for this test (CSN 5/17/2012), but it has not yet decided on a platform. "We have a few other ideas," Hofmann said.
The company is not aware of any competition in Europe at the moment for its non-invasive trisomy 21 test. Hofmann said she expects that the outcome of the ongoing patent disputes between Sequenom and its competitors Ariosa, Verinata, and Natera "will have an impact on Europe" regarding the ability of others to offer a similar test. "But right now, we are alone."