Sequencing foetal DNA extracted from a pregnant woman’s blood to detect chromosomal abnormalities is not a new idea, such tests having been commercially available since at least 2011. But approaching changes to the regulation of diagnostics in the US looks to be prompting an interesting divergence in business strategies from the handful of players involved.
Five companies sell prenatal blood tests in the US, all as unapproved lab-developed tests (LDTs). At some point the FDA is to take over regulation of LDTs and some players believe there are advantages to pre-empting this shift in authority, whereas others, aware that regulatory change happens slowly, are continuing along the LDT route.
The tests available in the US are not currently reviewed by the FDA. Instead, the sites at which the tests are performed are certified by the CMS, and the company can sell its testing services provided the testing is done at that one particular facility. That will all change when the FDA takes over regulation – though official legal changes could be years away (Vantage Point – FDA regulation of lab-developed tests could hurt smaller companies, June 19, 2013).
Roche, which entered the non-invasive prenatal testing (NIPT) space via the acquisition of Ariosa Diagnostics at the end of last year, is betting that it will see the greatest success if it undertakes the relatively long and expensive journey toward regulatory approval now. Sequenom, by contrast, has adopted the stance that unapproved tests have virtues of their own, mainly in terms of the ability to quickly offer additional screens.
With the timing of the new FDA oversight still up in the air, and reimbursement an ongoing negotiation, these opposing strategies could have implications for the emergence of any dominant position in this space in the future.
Race for US approval
Roche has confirmed to EP Vantage that it has definite plans to seek approval for the Harmony test it gained through the Ariosa acquisition. This is consistent with the strategy it employs for all its diagnostics (Roche seeks Harmony with Ariosa buy, December 2, 2014).
Interestingly, though, it might not be the first company to win a green light for a NIPT product: Illumina could get there first. Illumina bought its way into this sector two years ago with the purchase of Verinata Health, and ever since has been embroiled in patent litigation with rival Sequenom. But an agreement reached in December could speed Illumina ahead, Sequenom’s chief scientific officer, Dirk van den Boom, tells EP Vantage.
“Part of the arrangement we have with Illumina is they get access to our FDA-approved clinical studies so they can do their own IVD development,” Mr van den Boom says. “It’s maybe not the right conclusion that Roche will be the first.”
Illumina has said that it is working with the FDA towards the development of an approved test, though this may be somewhat different to its current verifi product.
Sequenom itself is content to offer its test on an LDT basis. This strategy has obvious financial advantages, but Mr van den Boom points out that these tests can also be nimbler, capable of reacting more quickly to patients’ demands.
“These assays change. If you look at the content we provide – from [trisomy] 21 and then adding 13 and 18 and six aneuploidies, the LDT route allows you to react to what the market needs and adjust on a quicker time pace,” he says. Adding additional testing capabilities to an FDA-approved test would require a separate approval process for the new product.
First to Europe
UK company Premaitha Health, meanwhile, has decided not to enter the fray in the US. The group is concentrating on Europe and is the recipient of the first CE mark for a NIPT product. Companies with LDTs can sell their testing services in Europe too, but the samples must be shipped to the US – or, in one case, China – for processing. Premaitha is selling a product, a diagnostic called Iona, rather than a service.
“The thing that differentiates us from all the other companies is that we are devoted to developing an in vitro diagnostic product and selling it to other laboratories so that they can perform the test themselves,” Premaitha’s chief executive, Stephen Little, tells EP Vantage.
Iona can determine the risk of a foetus having trisomies 13, 18 and 21 – Patau, Edwards’ and Down’s syndrome respectively. This is not as wide as some of the other tests in this space, but the UK group can use its CE mark as a selling point. Iona is the only test to have sought approval of European regulators; its receipt of this might persuade doctors and payers that it is the most reliable.
Moves by the likes of Roche and Illumina to receive US regulatory endorsement suggests that these players are interested in obtaining a similar advantage in the US.
One crucial consideration is that the cost of NIPT outstrips the combination of ultrasound and biochemical maternal blood testing used as the standard screen for Down’s and similar conditions today.
“I don’t think the price has to come down to the same price as the combined test before this test is cost-effective,” says Mr Little. He explains that, for every 25 women who screen high risk with the standard combined test, 24 results will be a false signal. To confirm the finding further invasive testing with amniocentesis or chorionic villus sampling, both of which are expensive and carry a risk of miscarriage, are necessary.
“We do expect that in countries where there’s a national provision of health [NIPT] may be offered on a contingent basis at first,” he says. He estimates that around 20% of women would be considered high-risk following standard testing and would then be offered NIPT.
Reimbursement in the US is trickier. Sequenom’s LDT Maternity21+ has a list price of $2,700 and is reimbursed at around $1,100, Mr van den Boom says. Ariosa/Roche’s Harmony LDT has a list price of around $800, and the others generally come in at around $1,500. The pricing difference is partly to do with the sequencing methods the tests employ; both Harmony and Natera’s test, Panorama, use a targeted approach, focusing on DNA from the chromosomes of interest, whereas the other players sequence the full genome.
It is possible that obtaining FDA approval might tempt a company to raise the price of its test – though it is unclear what reaction from payers this might prompt.
With Illumina having bought Verinata and Roche snapping up Ariosa it will be worth watching the smaller private firms such as Premaitha and Natera to see if they go the same way.
“There are a number of large diagnostic companies with an interest in prenatal screening,” Mr Little says, naming Thermo Fisher, PerkinElmer, Siemens, Abbott and Qiagen as large groups that “may be eyeing up the NIPT market”. He says that he would not be surprised to see the takeover trend continuing, though he stresses that the intention for Premaitha itself is not a sale.
It will take time for the NIPT market to grow in Europe, and changes at the FDA could yet shake up the US. But there is no denying that there is money to be made here, and further acquisitions or IP-sharing deals would be far from surprising.
An overview of NIPT technologies
||Trisomies 13, 16, 18, 21 and 22, foetal sex aneuploidies and microdeletions
||Trisomies 13, 18 and 21, sex chromosome triploidy, monosomy X, and microdeletions
||Trisomies 13, 18 and 21, aneuploidies and microdeletions
||Trisomies 13, 18 and 21, sex chromosome triploidy and monosomy X
||Lab-developed test; future FDA submission expected
||Trisomies 13, 18 and 21 and monosomy X
||Lab-developed test; future FDA submission expected
||Trisomies 13, 18 and 21
||CE marked in Europe; not yet available in US
Source: interviews and company websites
This article was updated on February 17th to include responses from Roche, Illumina and Sequenom
To contact the writer of this story email Elizabeth Cairns in London at email@example.com or follow @LizEPVantage on Twitter