Data Show that a Decrease in Tethys’ PreDx® Diabetes Risk Score (DRS) is Correlated with Lowered Risk of Diabetes

June 26, 2011

Data Show PreDx DRS May Be a Useful Tool to Identify Individuals Most Likely to Benefit from Intensive Lifestyle Intervention

EMERYVILLE, Calif.--Data presented today from an analysis of samples from the European Diabetes Prevention Study (EDIPS) showed that the PreDx® Diabetes Risk Score (DRS) is lowered by lifestyle intervention, which correlates to a reduction in the risk that patients will develop diabetes over time. The data further showed that patients with the highest DRS, who face the highest risk of diabetes, experienced the greatest benefit from intensive lifestyle intervention. The PreDx DRS is a multi-marker fasting blood test that assesses markers of inflammation, fat cell function, and glucose metabolism, and categorizes individuals as low, moderate, or high risk for diabetes conversion within 5 years. Developed by Tethys, the PreDx DRS has been shown to be more accurate than HbA1c or fasting glucose in predicting incident diabetes. The PreDx DRS test can be used to identify patients at risk for diabetes who are most likely to benefit from intensive lifestyle intervention, to reduce their risk of progressing to diabetes over the long term, and to monitor and potentially improve treatment outcomes.

The study also showed that a subset of individuals with the largest decrease in PreDx DRS at 1 year had the largest decrease in risk over 5 years relative to the control group. This observation provides the opportunity to change the intervention in the near term to increase long-term prevention and is the focus of future studies by the company and its collaborators.

The data were presented by Professor Jaakko Tuomilehto, MD, PhD, University of Helsinki, in a poster titled, “Changes in a Diabetes Risk Score Due to Intensive Lifestyle Intervention in the European Diabetes Prevention Study (EDIPS),” at the 2011 American Diabetes Association 71st Scientific Sessions, being held in San Diego.

Commented Dr. Tuomilehto: “PreDx DRS can be used to:

--identify those who are most likely to develop diabetes;

--monitor the efficacy of therapeutic interventions through follow-up DRS testing; and

--enable physicians to modify the intervention if a change in the DRS indicates the intervention has not been successful.

For instance, a focus on increased supervised compliance with an intervention program could be warranted. Used in this way, DRS can become a novel and valuable component of a diabetes prevention program.”

“These data are one of the first clinical demonstrations that the short-term lowering of PreDx DRS reflects an actual change in the risk of developing diabetes many years later, indicating a meaningful link between a decrease in a patient’s risk score and reduced diabetes risk,” said Mickey S. Urdea, PhD, chairman and chief scientific officer of Tethys. “Additional studies to elucidate the potential to improve outcomes and offer health economic advantages when PreDx DRS is used broadly in medical practice are clearly needed. Such studies could enhance our ability to stratify patients based on their level of risk to focus precious resources, determine their response to intervention and develop better methods to engage patients in behaviors that can delay or prevent progression to diabetes.”

About the Study and Results
In this study, 3303 longitudinal samples from 597 EDIPS participants, 248 of whom converted to type 2 diabetes during the study, were subsequently tested to evaluate changes in their multivariate PreDx DRS in response to intervention.

The PreDx DRS is related to the probability of developing diabetes within the next five years. The score ranges from <1 to 10 with a score of 5 corresponding to an absolute risk of 3.4%. Pre-specified cut points are provided that identify individuals with scores of less than 4.5 as low risk, scores greater than or equal to 8.0 as high risk with the remainder classified as moderate risk. In this analysis diabetes incidence (conversion) was based on WHO 1999 criteria using a single fasting glucose value ≥126 mg/dL) or a single two-hour glucose value ≥200 mg/dL. The full analysis set included every participant meeting the study enrollment criteria, who was not diagnosed with diabetes at baseline using WHO 1999 criteria, and for whom the DRS and outcome values were available. When assessing the benefit of different monitoring tools, a still-at-risk set consisting of participants who remained diabetes-free (prior to the next follow-up assessment) was used.

Key results from the study were:

--Intensive lifestyle intervention reduced the PreDx DRS score by 10% after 1 year of treatment (p=0.0002), indicating that the PreDx DRS is responsive to lifestyle intervention.

--This reduction in DRS is estimated to be a 29% reduction in relative risk (95% CI: 13-42%), which is very similar to the observed reduction in relative risk of 21%.

--The prognostic benefit of measuring DRS at 1 year remained significant even after controlling for change in fasting plasma glucose (FPG), change in HbA1c, and change in 2-hour glucose, indicating that change in DRS was a better predictor of outcome years later.

--When stratified by baseline tertile of FPG, HbA1c, DRS or FINDRISC (Finnish Diabetes Risk Score) participants in the highest tertile of DRS showed a 37.4% reduction in diabetes risk in response to intervention (p=0.004). When stratified based on only FPG (p=0.14) or HbA1c (p=0.87), the benefits of intervention are not significantly different from controls. The benefit is also seen in the upper tertile of FINDRISC (31.7%) and is slightly lower than with PreDx DRS, but is not significantly different. This indicates that DRS could be a useful tool for identifying individuals most likely to benefit from intensive lifestyle intervention.

--Participants categorized as “high risk” using PreDx DRS showed a 33% reduction in incident diabetes in response to lifestyle intervention.

--Study participants with a high (DRS ≥8.0) baseline risk who received lifestyle intervention and were monitored for effectiveness showed improved outcomes (p=0.003). When the participants who responded best to intervention (highest tertile of change in DRS) were differentiated from non-responders, the responders demonstrated an 87% (95% CI: 77-98%) diabetes free survival rate after 4 years (when intensive lifestyle intervention was stopped) compared to 62% (52-74%) for non-responders which is similar to the control value of 53% (45-63). This observation suggests that the PreDx DRS could be an effective monitoring tool, affording the opportunity to review and possibly change an unsuccessful intervention.

--In additional studies examining the cost effectiveness of PreDx DRS, results suggest that the PreDx DRS may be cost-effective relative to the use of PreDx DRS to identify an individual’s future risk of developing type 2 diabetes and consequent preventive intervention. Further validation is needed concerning the cost-effectiveness and acceptability of such monitoring assessed in routine practice.

A copy of the poster presented today is available from Tethys upon request.

About PreDx® Diabetes Risk Score
The PreDx Diabetes Risk Score (DRS) provides enhanced risk stratification through the measurement of multiple biomarkers linked to pathways of diabetes progression. PreDx DRS was developed using a unique approach to quantifying biomarkers suspected of playing roles in diabetes development. Tethys methodology enabled evaluation of many biomarkers utilizing very small amounts of blood from select and well-characterized large study cohorts with known diabetes outcomes. The company then determined the combination of these biomarkers with an algorithm that best identified an individual’s risk of developing type 2 diabetes within five years. PreDx DRS has been validated by the Tethys Clinical Laboratory (TCL) in several large populations. The test uses standard immunoassay and clinical chemistry formats, sample collection and shipment methods. Currently performed exclusively by the CLIA-certified TCL, the test generates a Diabetes Risk Score between 1 and 10 that corresponds to an absolute percentage risk of developing disease within five years. For more information about PreDx DRS, please visit www.predxdiabetes.com.

About Tethys
Tethys is a cardiometabolic diagnostics company that creates and commercializes breakthrough biomarker-based blood tests that predict imminent disease risk and enable targeted intervention to preempt the onset of chronic conditions such as type 2 diabetes. Tethys introduced its first product -- PreDx® Diabetes Risk Score -- to the market in 2008, and initiated sales in 2009. The Tethys PreDx platform includes products in development to determine risk for first-time heart attack, osteoporotic fracture and other cardiometabolic diseases with the goal of improving health outcomes and reducing the devastating economic impact that debilitating, preventable diseases have on individuals and society. The PreDx DRS is performed solely at the Tethys Bioscience Clinical Laboratory in Emeryville, CA. For more information about Tethys and PreDx DRS, please visit www.tethysbio.com.