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Orig3n's Purchase of Interleukin's CLIA Lab May Appease CMS, But Some Question Plans for Test Assets

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NEW YORK (GenomeWeb) – Orig3n's purchase of Interleukin Genetics' laboratory for an undisclosed sum last week gives it access to a CLIA-certified laboratory that will allow it to overcome regulatory restrictions it has recently faced from the Centers for Medicare & Medicaid Services.

Orig3n conducts research on regenerative medicine and aims to give consumers direct access to their genetic information. The company has held promotions for its consumer genetic tests at sports events around Boston. However, the company had to nix its plans to offer free DNA testing at a Baltimore Ravens football game in September after the promotion attracted the attention of CMS and the Maryland Department of Health. 

Maryland residents can't purchase direct-to-consumer (DTC) testing that provides health information unless it has been approved or cleared by the US Food and Drug Administration. Meanwhile, CMS makes sure that labs testing human biological samples and reporting results back to people for health-related purposes or for the treatment, diagnosis, and prevention of disease are following federal standards outlined in the Clinical Laboratory Improvement Amendments (CLIA).

Orig3n confirmed media reports that it had received a letter from CMS because it wasn't performing its DTC testing in a CLIA-certified lab. Specifically, CMS flagged 18 genes that it was analyzing and reporting to consumers that had to be performed in a CLIA-certified facility.

The CMS letter "was the first time that any clear guidance was given regarding specific genes and requirements for CLIA/non-CLIA," Orig3n CEO Robin Smith said in an email to GenomeWeb. The company immediately complied with CMS' recommendations, though Smith said that for the past 12 months, "Orig3n had been on a path to fully certify its lab and was nearing the completion of those efforts when we received the notification."

COO Kate Blanchard said that the company now plans to move all genetic testing to the CLIA-certified lab it acquired from Interleukin. In a statement announcing the acquisition, which closed Nov. 22, Orig3n noted that Interleukin's genotyping lab has the capacity to analyze more than 1 million samples each year. 

Discussions between Interleukin and Orig3n had been going on well before CMS sent its letter, according to Smith.

"We purchased Interleukin Genetics because it has core technology to help us expand and grow rapidly as we work to meet our organization’s goals," Blanchard said in an email. She added it was too early to comment on commercialization plans for the 18 genes that were the focus of CMS' letter. 

'Natural Alignment'

In addition to the CLIA lab, the acquisition also gives Orig3n access to Interleukin's genetic tests, particularly a test for gauging gum disease risk that a number of experts have criticized for lacking clinical validity. They worry that current gaps in the regulation of lab tests will allow Orig3n to resuscitate these tests. Orig3n hasn't yet decided whether it will commercialize Interleukin's tests but is evaluating the company's products.

Orig3n is "looking at the entire Interleukin portfolio and implementing the tests if and when we decide it is appropriate," Blanchard said.

Although Orig3n told GenomeWeb that it hasn't made any commercialization decisions with regard to Interleukin's tests, in a statement announcing the acquisition, Smith said, "Once we met with Interleukin Genetics, we saw a natural alignment between the two organizations regarding our shared commitment to a future of personalized health. With our trajectory of accelerated growth, we couldn't imagine a better fit for acquisition."

Waltham, Massachusetts-based Interleukin announced in July that it would lay off 63 percent of its workforce and pursue strategic alternatives, such as a sale of the firm and its assets. The company said at the time that it was $5.6 million in debt, including $4.9 million in accounts payable and contract severance obligations. 

Specially, Interleukin had said it would halt its Ilustra Inflammation Management Program, which featured a genetic test to identify people at high risk for "elevated systemic inflammation." The company claimed this test could enable early identification of those at high risk for chronic diseases associated with inflammation, such as gum disease, heart disease, and diabetes. Interleukin also sold genetic tests for nutritional needs, weight management, heart health, and bone health.

The pipelines of both companies point to a common interest in the use of genetics to guide healthier lifestyles. For example, Orig3n currently sells a genetic test for evaluating how one's body responds to certain foods and nutrients, and another that claims to help people understand how their DNA affects their "fitness potential," each priced at $149.

Interleukin, meanwhile, offered a genetics-based weight management program that it claimed could help determine if someone was likely to benefit from a low-fat or low-carbohydrate diet, and whether they'd "most efficiently lose weight" with "normal or more vigorous exercise." A nutritional needs genetic test claimed to identify DNA variations involved in vitamin B metabolism and management of oxidative stress.

Interleukin marketed these tests, as well as tests for bone health and heart health (which it sold before the Orig3n deal) under its Inherent Health line of products. The US Food and Drug Administration sent Interleukin an "untitled letter" two years ago asking why some of these tests were being sold without the agency's approval, particularly since the Inherent Health line of tests were being offered directly to consumers. The FDA exercises enforcement discretion over lab-developed tests (LDTs) performed at a single lab, leaving lab oversight to CMS under CLIA. However, this policy does not extend to health-related DTC genetic tests. 

After discussions with the FDA, Interleukin said it was allowed to continue selling its bone and heart health tests as physician-ordered LDTs, as long as it stopped marketing them DTC. The company's PerioPredict test —which the company later rebranded as Ilustra — fell under FDA's enforcement discretion policies for LDTs. 

PerioPredict also received conditional approval from the New York State Department of Health, which the FDA recently accredited as a third-party reviewer of certain IVDs, including next-generation sequencing tumor profiling tests. This allows companies with NYSDOH approval for these specific types of IVDs to use the submission to the state regulator to apply for FDA 510(k) clearance. 

“I am extremely concerned that the FDA would delegate regulation to the NYSDOH given the lack of transparency there," said Scott Diehl, a genetics researcher at Rutgers School of Dental Medicine and a longtime critic of Interleukin.

Diehl co-authored a reanalysis of a key clinical validity study underlying PerioPredict, which found that the test couldn't predict which patients were at greater risk for gum disease, and forwarded this reanalysis to the leadership at NYSDOH requesting they rescind conditional approval of the test. NYSDOH leadership maintained their stance on the test, replying that "there continue to be articles published that support the association," without revealing which specific studies were used to make that determination. 

With regard to its weight-management test, Interleukin had previously said it was continuing discussions with the FDA to determine "appropriate next steps, if any." Blanchard didn't answer questions about how the regulatory discussions were ultimately settled on that front, but only reiterated that it's too early to tell if Interleukin's test will fit Orig3n's platform.

Significant concerns

Orig3n declined to answer questions about how it planned to manage the Ilustra program, which has raised significant concerns in the dental community. These concerns stemmed from the reanalysis by Diehl and colleagues of PerioPredict's clinical validity data, an editorial accompanying that reanalysis from the highly cited scientist John Ioannidis, and published commentary from experts in dental research questioning the methodology of studies Interleukin used to support claims that Ilustra could detect elevated systemic inflammation. 

In response to questions from GenomeWeb about these concerns, Orig3n noted, "that was simply before Orig3n's time with the company and they do not have a part in it."

Despite the criticism, Interleukin had maintained that its tests were based on sound science, and further claimed that a risk-based model including PerioPredict and well-known risk factors such as smoking and diabetes status could be used to decide which patients get one, two, or more cleanings per year, and save insurers $4.8 billion. 

The data swayed Interleukin investor Delta Dental and stockholder Amway. Several Delta Dental organizations had included Interleukin's test as part of risk assessments to determine the number of covered cleanings employees can receive per year, and Amway agreed last year to offer the test to its 5,000 employees as part of a wellness program.  

Amway is a large employer in the Grand Rapids region, and local dentist Chris Smiley has seen several Amway employees who received Interleukin's gum disease risk test, got a negative genetic test result, but had heavy inflammation, bone loss, and other obvious clinical evidence of periodontal disease. "But, by gosh, they had this genetic test and it came back negative, so [they'd question] why they are receiving additional care when they genetically tested not to be at risk," Smiley said, reflecting that these types of incidents strained the doctor/patient relationship.

Smiley said other dentist colleagues in the area had patients with no clinical signs of gum disease, who showed up with positive test results indicating they were at risk and would benefit from additional cleanings. "It's very difficult to ethically perform more cleanings based only on the results of the genetic testing but no clinical signs," Smiley said.

While Orig3n has not yet disclosed its plans for the Ilustra program, the fact that it “would even consider possibly taking the Ilustra test back out to market in the face of such grave scientific invalidity is deeply disturbing," Diehl said.

Smiley and other Michigan dentists were also troubled when patients came in with results from Interleukin's nutritional needs genetic test, which the company sold through Amway. To Smiley, the whole setup seemed to be a vehicle for peddling Amway's nutritional supplements line. "They'd take the tests and show up in the practitioner's office with a long list of nutritional supplements they're supposedly susceptible to," he recalled. "We'd be challenged to draw any meaning from the test results."

Diehl harbors similar doubts about the scientific basis for Interleukin's weight-management test. A search for clinical evidence on this test yielded a 2010 Wall Street Journal article discussing a study involving 133 overweight women, which showed that those genetically predisposed to benefit from a low-carbohydrate diet or a low-fat diet lost more weight compared to women on these same diets but without these genetic predispositions. 

The WSJ article noted that these results were presented at an American Heart Association medical conference but needed further confirmation in larger evaluations. GenomeWeb reached out to Kenneth Kornman, Interleukin's founder, to find out about the published studies underlying this test. "I have not been employed at Interleukin nor a member of the Board for more than three months," Kornman replied over email. "I am not familiar with the transaction with Orig3n or the status of any of Interleukin’s test portfolio."

Christopher Gardner, director of nutrition studies at Stanford Prevention Research Center and a co-author on the 133-patient study, said this week that the original study was not published because the journal wanted the findings replicated first. He did conduct a large study involving 600 patients in attempting to replicate the earlier findings. 

In this trial, Gardner's team used an 850,000 SNP genotyping array that will enable evaluation of the same genetic markers as in Interleukin's test and allow exploration of other SNPs that might predispose people to benefit from a low-fat versus low-carb diet. Although the study is completed, Gardner said he couldn't discuss the results because they're in the process of being published.

"Years later, and millions of dollars in diet tests sold by Interleukin in the meantime, we're still waiting for the larger study," Diehl said.

According to filings with the US Securities and Exchange Commission, Interleukin sold its Inherent Health brand of tests, which included the weight management test, through an online marketing arrangement with Amway. Test sales through this arrangement accounted for 45 percent of $1.44 million in 2015 revenues and 24 percent of $2.51 million in 2016 revenues. 

Interleukin also reported in SEC filings that in 2012 and 2013 an affiliate of Alticor, Amway's parent company, placed purchase orders for weight-management test kits totaling $3.3 million. The company also inked licensing deals with Alticor affiliates to sell this test in Europe, Russia, and South Africa, which brought in $191,000 in 2015 and $199,000 in 2016.

While Orig3n may decide not to integrate Interleukin's tests into its platform, the acquisition concerns Diehl and Smiley precisely because the two companies seem to be aligned in their assets and goals. While the acquisition may provide financial relief to Interleukin's investors, like Amway, Smiley questioned how this will impact consumers and patients.

Amway heir Richard Devos Jr. is chairman of Spectrum Health System's board, a healthcare organization that serves West Michigan, and which recently launched Spectrum Health Ventures to manage a $100 million fund on its behalf. In June, Orig3n raised additional funds and named SHV as one of its investors.

Smiley questioned why SHV would invest in a firm like Orig3n, focused on the consumer genetics market, especially since genetics experts have also questioned the value of its tests, such as the one on fitness potential. "I'm not sure how Orig3n's mission and the genetic tests they offer fits into healthcare being delivered in our community," he said. "It seems to be an investment that was made on the accounting side of the ledger."