By Julia Karow
Sequenom has selected the Illumina HiSeq 2000 platform to run its commercial non-invasive trisomy 21 screening test at launch, currently planned for the fourth quarter of 2011, according to a company official.
At the UBS Global Life Sciences Conference in New York this week, Ron Lindsay, Sequenom's senior vice president of R&D, said that the company recently completed a technical validation study of its test (IS 8/10/2010) and will soon embark on a clinical validation study.
The company sees a large market opportunity for the test, which it hopes will replace current screening tests — a combination of serum markers and ultrasound measurements — that have low sensitivity and specificity. Its own screening test will be non-invasive and will use next-generation sequencing to measure an excess of fetal DNA from chromosome 21 in the mother's blood. Ideally, Lindsay said, the test would be similar in accuracy to amniocentesis, an invasive procedure that is the current gold standard for trisomy 21 testing and has a sensitivity and specificity of more than 99 percent.
Lindsay said that results from a study of 800 patients conducted by Sequenom's collaborator Dennis Lo in Hong Kong, which he presented last November, indicated that the use of massively parallel sequencing "could give very accurate results." The study is expected to be published within a month. At the time, the cost of the test was "well less" than $1,000, he said.
Over the last year or so, Sequenom has been evaluating how the test could be offered commercially, and has found that "the sequencing itself, technically, is very feasible," he said (IS 5/18/2010).
"The important thing, in a commercial setting, is trying to set up a whole process … to do this in a robust manner," Lindsay said, and Sequenom researchers have been working on sample processing, library preparation, sequencing, and data analysis "to assess whether a commercially feasible test can be derived, and we're comfortable on moving forward."
Sequenom just completed an internal technical validation or "locked assay" study of the test, in which it analyzed about 450 samples, including about 40 trisomy 21 samples. "The purpose of that study was not for clinical statistical power but just to make sure all the analytical steps and improvements we have made in the last year, when run in a single, sort of standard week in a lab, would work well together," Lindsay said.
He did not report any results from the study but said it will soon be submitted to a journal, with the aim of being published in early 2011.
In the meantime, Sequenom is preparing to embark on a clinical validation study of the test, which will commence "as soon as this has gone through our internal procedures for approval."
The study will be performed on samples collected by Sequenom and academic collaborators over the last two years for two academic studies, one aiming to collect about 80 trisomy 21 samples in a background of about 5,000 normal samples, the other aiming to collect about 200 trisomy 21 samples.
For the validation study, which is blinded, Sequenom will receive the samples — which have all been analyzed by amniocentesis or chorionic villus sampling — from a third-party storage site and will have no access to any clinical information. After analyzing the samples in its CLIA lab, Sequenom will send the data back to its collaborators for data analysis and publication. Depending on the results, Sequenom hopes to launch the trisomy 21 test as a laboratory-developed test in the fourth quarter of 2011.
Lindsay said the company's ultimate goal is to gain premarket approval for the test from the FDA. For that, it has been collecting samples "that we hope the FDA will permit us to use for PMA, and we will, in the near future, have discussions with the FDA." He said that the company is preparing a pre-investigational device exemption submission, and once the trial has been designed, it plans to go ahead with a PMA study.
Lindsay did not comment on the process for securing FDA approval of the sequencing platform on which the test will run, but at the Morgan Stanley Global Healthcare conference in New York last week, an Illumina official said that the company is currently evaluating whether to submit the HiSeq system for 510(k) approval by the FDA (see story, this issue).