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Myriad's Crescendo Shares New Data Confirming Vectra DA's Ability to Predict RA Joint Damage

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NEW YORK (GenomeWeb) – Crescendo Bioscience, a subsidiary of Myriad Genetics, presented new data this week at the American College of Rheumatology annual meeting showing its Vectra DA test can predict progressive joint damage in rheumatoid arthritis patients better than other clinical markers of disease activity like C-reactive protein (CRP).

Crescendo has presented similar data from a number of different studies, including a large retrospective study of patients in the Swedish Farmacotherapy, or SWEFOT clinical trial, which demonstrated that Vectra DA scores taken when patients began treatment were predictive of later joint damage over the following year as measured by radiographic imaging. A previous study, of the Leiden Early Arthritis Cohort, showed that patients with a high Vectra DA score were at a six-fold higher risk of disease progression than those with a low Vectra DA score.

Eric Sasso, VP of medical and scientific affairs at Crescendo, told GenomeWeb that the new data, presented in an oral session at the ACR meeting today, is the first of its kind from a US-based study, the Brigham and Women's Rheumatoid Arthritis Sequential Study, or BRASS.

Vectra DA is a blood-based test that measures the levels of 12 RA-associated proteins. The test classifies patients using a score between one and 100 intended to help doctors determine whether a patient has high, moderate, or low RA disease activity.

In BRASS, Crescendo studied 143 patients from the registry cohort, calculating their Vectra DA score at the point of entry into the trial, as well as several other measures of RA disease activity, including protein markers like CRP, DAS28-CRP, CDAI, SDAI, and RAPID3.

The study also X-rayed participants' hands and wrists at the initial visit, and then again two years later. The researchers were thus able to measure the relationship between initial Vectra DA score, or the level of any of these alternative markers, and the amount of damage to joints after two years.

According to Crescendo, the results showed that Vectra DA was the best independent predictor of disease progression when compared with the other measured biomarkers, based both on radiographic measurements and on patients' reported outcomes.

"Our main finding was that Vectra DA score is associated with and predictive of risk for future joint damage, which reinforces what has been seen in others studies ... so the strength of this is that it proves that what we were seeing before is real," Sasso said.

He added that it is also a much more comprehensive comparison of Vectra DA and other measures of disease activity.

The company reported at the meeting that among the measured disease activity markers the odds ratio for predicting progression was highest for Vectra DA and lowest for RAPID3. The predictive accuracy for Vectra DA, as measured by the area under the receiver operating curve, was 0.75, while for RAPID3, the AUC was only 0.5.

Some other markers, CRP especially, also correlated strongly with joint damage progression. The AUC for CRP was 0.71, nearly as high as Vectra DA. The two measures also had identical odds ratios, of 2.88. But according to the study researchers, Vectra DA appeared to provide predictive information above and independently of these other measures.

For example, when the team looked at the subset of patients with low CRP at baseline, a substantial number of those with high Vectra DA scores within that subset, about 35 percent, showed radiographic progression after two years, while only about 8 percent of those with low or moderate Vectra DA scores progressed similarly.

Initially, Crescendo focused marketing of Vectra DA as a disease monitoring tool but more recently began presenting data supporting the test more directly as a tool to guide therapy by showing it can predict which patients will suffer more rapidly progressing joint damage and which will not. A more accurate assessment of which early RA patients will show this progression could help doctors direct them to the right types of treatments more quickly and efficiently, while avoiding unnecessary treatment in those unlikely to progress.

In addition to this, the company has also begun to actively collect additional data to demonstrate that Vectra DA can also predict specifically which patients are likely to benefit from different therapeutic strategies after they fail to respond to methotrexate, the initial therapy of choice.

At the 2014 European League Against Rheumatism (EULAR) Annual Congress earlier this year, Karen Hambardzumyan of Sweden's Karolinska Institute presented a follow-up study of the SWEFOT trial, which found that in patients who had inadequate clinical responses to three months of methotrexate, some showed changes in their Vectra DA score, while others did not.

Those whose Vectra DA score dropped the most after three months had a higher likelihood of response to triple (DMARD) therapy — based on achieving low DAS28 or good EULAR response criteria — than those who didn't show molecular changes after three months of methotrexate.

Patients with smaller decreases in their Vectra DA score, meanwhile, were more likely to respond to anti-TNF therapy.

Hambardzumyan shared posters presenting updated analyses of these SWEFOT studies at the ACR meeting this week, as well as other data previously shared at EULAR, which suggested that Vectra DA might offer a way for pharmaceutical companies and researchers to recruit more patients into RA drug trials without harming their chances of success with a particular therapy.

In another novel presentation at ACR, researchers also showed data on how Vectra DA score corresponds to ultrasound measurements of disease progression. Radiography is the mainstay in assessing RA's progressive damage to joints, Sasso said. But Crescendo has also worked to show that the test can predict damage as assessed by other tools, like MRI.

Finally, at ACR Crescendo also shared a poster with data on its first exploration of Vectra DA's utility outside of rheumatoid arthritis.

In this study, researchers from the company analyzed a variety of disease activity measures in 40 patients with axial spondyloarthritis, including CRP and the ankylosing spondylitis disease activity score (ASDAS), in addition to Vectra DA score.

They found that Vectra DA score was indeed associated with the other available measures of clinical disease activity in patients with axial SpA, correlating most strongly with the ASDAS.

According to Sasso, Crescendo is now looking for opportunities to replicate or extend the SWEFOT findings of Vectra's ability to predict which drug strategy should be used in patients who fail to respond to methotrexate. The BRASS registry is probably not the best source, he said, but the company has several ongoing studies where patients are assessed more frequently that could prove valuable in this regard.

"Another area where we have studies being completed or analyzed now is [cohorts] where patients have done extremely well, gone into remission or into low disease activity and their TNF-antagonist is withdrawn or reduced," Sasso added. "We are very interested there in learning if Vectra DA score at the time of discontinuation of therapy can predict who will do best."

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