As several companies are vying for a share of the noninvasive prenatal testing market in the US, Berry Genomics has been focusing its efforts on providing sequencing-based NIPT in China.
The company, which is based in Beijing and has additional facilities in Shanghai and Qingdao, was founded in 2010 by a group of Chinese genomics researchers with expertise in next-gen sequencing, according to CEO Dai Xing Zhou. Besides prenatal testing, the firm is also interested in early cancer detection in blood.
Traditional prenatal serum screening has high error rates, and invasive prenatal testing is accurate but comes with a risk of miscarriage or infection. "Recognizing the gap between the large demand and the unsatisfactory screening and diagnostic technologies, we devoted ourselves to developing a novel, noninvasive and accurate prenatal detection technology to reduce the birth defect rate in China," the firm noted in its printed informational material. "Our non-invasive DNA prenatal test (NIPT) was developed under such motivation."
In late 2011, Berry Genomics started offering noninvasive prenatal testing for chromosomal aneuploidies and has performed more than 50,000 tests so far. Demand for the assay, called BambniTest, is strong, according to Zhou, and the company expects to perform more than 100,000 tests this year.
This volume is on par with what US-based NIPT companies have reported. Sequenom claims it has reached an annualized run rate of 120,000 tests, while Ariosa's annualized run rate is 100,000 tests.
Like Sequenom and Verinata, Berry sequences cell-free genomic DNA from maternal plasma, which contains fetal DNA, and looks for an overrepresentation of DNA from certain chromosomes. The company currently runs its test on Illumina's HiSeq 2000, processing samples at its Beijing and Qingdao facilities. A third facility, in Shanghai, will become operational "very soon," according to Zhou.
Turnaround time is currently 10 business days, which the firm plans to reduce to five days by making each step in the testing process more efficient.
Zhou told Clinical Sequencing News via email that the company has invented new methods around its test and has filed several patent applications, most of them worldwide. Berry has also been in discussions with several parties regarding other intellectual property surrounding NIPT, which he said is "a complicated and sensitive matter." He declined to comment on the firm's current legal position.
Berry completed its first financing round in the fall of 2011, raising an undisclosed amount from Legend Capital, a venture capital firm based in Beijing. Zhou said the firm, which had almost 300 employees as of last year, has no immediate need for additional funding.
Berry focuses on the Chinese market at the moment, providing testing in 30 provinces and districts, and collaborating with more than 350 maternal hospitals.
Right now, the company offers the test mainly for high-risk pregnancies. Zhou said that invasive testing is offered to high-risk pregnant women first as a standard of care, but if a woman refuses such testing "due to various reasons," she is offered the noninvasive test.
The estimated number of advanced maternal age and other high-risk pregnancies in China is about two million per year, according to Zhou, about three times the size of the US market. The overall market opportunity, however, is about the same as in the US — an estimated one billion dollars — since pricing needs to be lower in China. Berry charges patients around $500 per test at the moment, an out-of-pocket expense.
In collaboration with academic partners, Berry has studied its BambniTest in two clinical trials so far.
Results from a retrospective trial, led by the State Key Laboratory of Medical Genetics at Xiangya School of Medicine of Central South University in Changsha, were published online earlier this month in Prenatal Diagnosis. The study, based on 435 samples from high-risk pregnancies, found that the test accurately identified all 67 chromosomal aneuploidies, including trisomy 21, trisomy 18, trisomy 13, trisomy 9, monosomy X and others, with two false positive results. The overall sensitivity was 100 percent and the detection specificity was 99.71 percent. The study also concluded that normalization of chromosome representation against GC content is "the key issue" to ensure accuracy.
A second, prospective clinical trial tested the assay in more than 2,000 pregnancies, comparing it with serum screening and karyotyping. Results from that study, which have been submitted to a journal for publication, are "as good as one can expect," Zhou said, and are "very close to the findings in clinical practice."
Berry's main competitor in China — and possibly its only one at the moment, according to Zhou — is BGI. According to its website, BGI Health offers non-invasive prenatal testing to detect aneuploidies in chromosome 21, 18, 13, and others for pregnancies between 12 and 24 weeks of gestation, recommending it for high-risk pregnancies and other indications. Turnaround time is seven days on average, with regional differences, and is expected to decrease in the near future with technology improvements. Last year, BGI also partnered with a fetal medicine center in the Czech Republic to introduce its noninvasive fetal trisomy test, called NIFTY, in the Czech and Slovak Republics (GWDN 10/16/2012).
"At this stage, it is too early to tell who owns the majority of the market share" in China, Zhou said. "It is more important to make sure the market is developed in a healthy way."
In the near future, Berry Genomics also plans to provide array CGH for invasive prenatal testing and for pediatric screening and diagnosis. To that end, the company has partnered with Baylor College of Medicine, an expert in array CGH testing, which has been providing it with its array technology and access to its database of more than 50,000 cases, Zhou said.
Also, by combining array CGH and noninvasive prenatal testing, Baylor and Berry are planning to "join efforts in developing the technologies to detect micro-deletions/micro-insertions non-invasively," Zhou said.
According to Arthur Beaudet, chair of molecular and human genetics at Baylor College of Medicine, both partners are interested in such research, and Baylor has "a lot of respect for [Berry's] sequencing expertise in this area," following a visit of the company in China last year. But Baylor is "not actively doing anything with Berry Genomics on the noninvasive front at the moment," he said.
"We certainly want to see noninvasive prenatal diagnosis that can detect everything that invasive prenatal diagnosis can detect," Beaudet told CSN. "No one in the world is to that point at the moment, although I think it's widely expected that various laboratories will achieve that within the coming year or so."
So far, Baylor has been focusing on isolating fetal cells from maternal blood rather than analyzing cell-free DNA from maternal plasma, he added.
Berry Genomics is also putting "a lot of effort" into developing noninvasive prenatal tests for single-gene disorders with high prevalence in China, according to Zhou. For example, the incidence rate for thalassemia is very high in southern China, he said, with up to 17 percent of the population being carriers in some areas.
Developing NGS-based cancer detection assays from circulating tumor DNA in blood is another area the company is interested in. "The technologies developed for prenatal detection will likely be applicable to cancer, with higher sensitivity and specificity," Zhou said, noting that developing these "will take some time" and that clinical trials will be needed before such testing can be offered more generally.