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Good Start Genetics Data Supports NGS-based Pan-Ethnic Carrier Screening

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NEW YORK (GenomeWeb) – Good Start Genetics presented data last week at the American College of Obstetrics and Gynecologists' annual meeting from two studies it carried out in collaboration with the Texas Fertility Center in Austin evaluating the clinical effectiveness of its pan-ethnic carrier screening test, GoodStart Select.

The abstracts showed that the test could detect carriers who would have been missed by other technology and also made the case for universal screening for spinal muscular atrophy, demonstrating that the carrier frequency for SMA is nearly as high as for cystic fibrosis.

In one abstract, the researchers found that of 39,972 samples evaluated with Good Start's test, 1,948, or nearly 5 percent, of them were found to carry a pathogenic mutation in one of 14 disorders for which the test screened. Of those carriers, between 16 to 22 percent of them would have been missed with traditional screening methods.

In a second abstract, the researchers evaluated the carrier frequency for spinal muscular atrophy in patients undergoing in vitro fertilization and found that approximately one out of 59 individuals across ethnicities carried a pathogenic mutation.

Kaylen Silverberg, medical director of the Texas Fertility Center who led both studies, told GenomeWeb that the goal was to demonstrate the power of pan-ethnic carrier screening with next-gen sequencing.

"If you don't test for all the mutations and you miss what people might call a minor mutation, you run the risk of having a child affected with a serious disorder," Silverberg said.

In addition, he said that the SMA-focused study makes the case for universal carrier screening for the disorder. Currently, although the American College of Medical Genetics and Genomics does recommend universal screening for SMA, ACOG does not.

"The disorder affects one in 59 couples" and is "devastating and common," Silverberg said. "Testing should absolutely be available."

He thinks that it is just a matter of time before professional organizations make changes to the guidelines for carrier screening.

Silverberg said that he began using Good Start's test three to four years ago. Previously, he offered carrier screening with a variety of commercial tests, most of which relied on array-based genotyping or PCR. By contrast, Good Start's test uses molecular inversion probes to target coding regions and well-characterized non-coding regions of the genes, next-gen sequencing, and a novel assembly algorithm. The test was originally launched to target 14 disorders but has since been expanded to 23 disorders. In its clinical validation study, GoodStart Select demonstrated 99.98 percent analytical sensitivity, 99.9999 percent analytical specificity, and positive predictive values of 100 percent and 97 percent for common and novel SNVs, respectively.

Robert Rochelle, vice president of strategic marketing at Good Start Genetics, told GenomeWeb that since the abstracts were submitted, the company has evaluated additional cases. Now it has screened over 71,000 patients and identified 3,000 carriers. Similar to the abstract, between 15 percent and 26 percent of those carriers would have been missed by other technologies, Rochelle said.

Physicians that order GoodStart Select have the option of ordering testing for all 23 disorders, just one of the disorders, or any combination. The firm included disorders recommended in guidelines set by ACOG and ACMG, as well as societies supporting the Ashkenazi Jewish population.

Rochelle said that physicians often order screening based on population-specific recommendations. The most common combination is a three-pronged test screening for cystic fibrosis, fragile X, and SMA, Rochelle said. There are clearer guidelines around those disorders, he said, so many physicians order testing of just those three, while others opt to screen for all 23.

Silverberg said he predominantly orders the whole array of testing and thinks that is the direction the field is heading. Because globalization is making it possible to marry across populations, "the whole idea of ethnic-based testing is really going out the window," he said. A number of genetic disorders "used to be confined to certain ethnicities and that is just not true anymore," he added. For instance, he said, his laboratory is finding carriers of sickle cell anemia, found more often in individuals of African descent, who are of Asian ancestry, and finding individuals carrying pathogenic mutations for disorders that were more prevalent in the Ashkenazi Jewish populations in individuals who were clearly not of that ancestry.

Patients, too, are seeing the value of carrier screening, Silverberg said, and despite working at a fertility center, he said that couples now come in with no fertility problems but just want to be tested for their carrier status. Those individuals currently make up a small fraction of his patients, about 5 percent, but that number is growing, he said.

The guidelines for carrier screening are also evolving as expanded carrier screening — testing for multiple disorders at once — is proving to be more cost effective than screening for one disorder at a time. Although professional organizations have stopped short of endorsing such tests, earlier this year, ACMG, ACOG, the Maternal Society for Maternal-Fetal Medicine, the National Society for Genetic Counselors, and the Perinatal Quality Foundation issued a joint statement on the matter that aimed to address a number of issues around expanded carrier screening tests and to give guidance to obstetric care providers until more formal recommendations and guidelines are in place.

Rochelle said that one goal of Good Start's publications is to demonstrate clinical utility and cost-effectiveness of the test, which he hopes will drive professional organizations to create guidelines around screening and thereby encourage insurance companies to reimburse for the test. Thus far, he said that reimbursement has been a mixed bag. Good Start has a "number of insurance contracts and we're adding to the list every day," although it is still a challenge, he said.

He also noted that Good Start just completed a cost-effectiveness study that it is preparing to publish in a peer-reviewed journal.

Good Start has focused predominantly on the IVF market for its GoodStart Select test, but Rochelle said the firm is looking to expand in three different ways.

First, it is pushing beyond the IVF market with its GoodStart Select test and into the general Ob/Gyn market and international market.

Second, Rochelle said the firm is developing "complementary" products to carrier screening for the IVF market including preimplantation genetic screening and diagnostic tests and also a noninvasive prenatal test.

It made its first move in that direction last year when it struck a deal with Valencia, Spain-based IviGen to offer reproductive genetics products and services. It is now selling Ivigen's PGS and PGD products, as well as an endometrial receptivity array test, which helps determine the best time for implantation. Rochelle said that the company is also developing an NGS-based version of the PGS test, which could be more cost-effective.

The company also licensed technology from Johns Hopkins University called FAST-SeqS for Fast Aneuploidy Screening Test-Sequencing System. Good Start originally licensed the technology for preimplantation genetic screening, but has since expanded on the agreement to include noninvasive prenatal testing.

Rochelle declined to give a time frame for when the company would enter the NIPT market and also declined to comment on whether it would have to license intellectual property from Sequenom and Illumina to offer the test, saying only that the company "would not have done the deal if we didn't think we could apply the technology."

Finally, he said that the company is expanding into the broader clinical NGS market and looking to develop products both in reproductive health and other therapeutic areas. 

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