Sequoia Genetics, a Russian molecular genetics company, has launched a clinical trial of a sequencing-based test that screens for three congenital metabolic diseases: cystic fibrosis, phenylketonuria, and galactosemia. Sequoia has developed the test on Life Technologies' Ion Torrent PGM using its AmpliSeq technology and expects to have trial results in September.
Alexander Pavlov, CEO of Sequoia Genetics, told Clinical Sequencing News that the company decided to focus on those three conditions because Russia requires that all newborns be screened for them.
Currently, newborns are initially screened with a biochemical analysis, said Pavlov, but the results of that analysis can often yield a lot of false positives and false negatives because the markers are not very strong, which can sometimes lead to a "suite of testing," all of which have low sensitivity.
The goal with the sequencing-based test is to design a test with higher sensitivity that can lead to an accurate diagnosis more quickly. Currently, said Pavlov, the average age of diagnosis for cystic fibrosis in Russia is three years old.
The sequencing-based test will include 252 mutations across all three disorders, 158 of which are related to cystic fibrosis. The test was custom-designed using Life's AmpliSeq technology and covers 20 kilobases, said Pavlov. For the trial, Pavlov said 48 samples would be pooled together on a 316 chip.
Sequoia has partnered with three different European laboratories: the Institute of Molecular Pathology and Immunology of the University of Porto, the StabVida company in Portugal, and the Center for Genome Research at the University of Liverpool in the UK. Each lab will run 192 samples.
Pavlov said that by running the test at three different laboratories, the company will establish not only diagnostic sensitivity and specificity, but also inter- and intra-laboratory reproducibility and analytical performance.
Following the clinical trial, Pavlov said that the next step would be to apply for regulatory approval. Initially, he said Sequoia would seek CE marking in Europe for the test, and eventually approval from the Russian government and potentially US Food and Drug Administration clearance.
Pavlov said the company would have different commercialization strategies for different markets and countries, but would sell the test as a kit rather than a service. He added that pricing had not yet been determined and would also depend on the level of multiplexing.
Aside from the panel itself, Sequoia has developed its own software and variant database, which Pavlov said would set it apart from other tests. Current variant databases contain misannotations, said Pavlov. "We've found dozens of mistakes in dbSNP and even in specific CFTR databases," he said. "We have changed these annotations, not only in our own database, but we are also publishing some data that should clarify some problems in these databases."
In addition to building its own database, he said the firm is developing software to simplify variant calling and report generation. The tools were designed with clinical geneticists in mind, Pavlov said, so that it should take "no more than 15 seconds to find out the pathogenic mutations."
He added that focusing on smaller gene regions enabled the bioinformatics to be simplified.
Compared to current biochemical screening methods, Pavlov said the sequencing-based test will yield a definitive result right away, so patients do not have to go through multiple tests over several years to gain a diagnosis.
If the test is validated in newborns, the company also plans to launch a test to evaluate carrier status of the three diseases in adults.
Once it commercializes its test, Sequoia will likely compete with Illumina, which just applied the CE mark to its cystic fibrosis assay that runs on its MiSeqDx system (CSN 7/3/2013).
Illumina has also submitted its MiSeqDx system and two cystic fibrosis assays to the US Food and Drug Administration for 510(k) clearance.