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MDx/CDx Focus: New Studies on Veracyte's Afirma, Allegro's BronchoGen; MyRA App Globally Launched


Veracyte Reports that Adding BRAF Mutation Testing Doesn't Improve Upon its Afirma Test

In a study published online last week in the Journal of Clinical Endocrinology & Metabolism, researchers from Veracyte and Centro Diagnostico in Italy investigated whether adding testing for BRAF mutations improves the accuracy of Veracyte's Afirma Gene Expression Classifier in assessing the risk of thyroid cancer in patients with ambiguous nodules.

Researchers led by Veracyte's Richard Kloos tested the BRAF V600E mutational status in DNA from 40 cytologically benign, 208 indeterminate, and 48 malignant thyroid nodules that were previously categorized by the Afirma Gene Expression Classifier as molecularly benign or suspicious. The study investigators correlated results from the molecular tests with blinded histopathological diagnoses.

The Afirma Gene Expression Classifier measures the expression of 142 genes to reclassify intermediate thyroid fine-needle aspiration specimens as either benign or suspicious for cancer. The test also analyzes 25 supplemental genes in order to classify nodules in rare cancer subtypes. BRAF mutations, meanwhile, have been linked to certain thyroid cancers.

In the study, Kloos et al. reported that they identified BRAF mutations in 2 out of 40 benign specimens, 36 out of 48 malignant specimens, and 10 percent of the 208 specimens in the intermediate category. The Afirma Gene Expression Classifier had deemed as "suspicious" all samples that were BRAF mutation-positive.

Among the 208 samples of intermediate risk, BRAF mutations were identified in two of 95 samples subcategorized as atypia of undetermined significance or follicular lesion of undetermined significance, one out of 70 follicular neoplasms or deemed suspicious of follicular neoplasms, and 18 out of 43 flagged for malignancy.

"BRAF mutations are uncommon in nodules with atypia of undetermined significance or follicular lesion of undetermined significance or follicular neoplasm or suspicious for follicular neoplasm cytology. Most cytologically indeterminate nodules that proved to be malignant were also BRAF negative, and all nodules that were false-negative by [the Afirma Gene Expression Classifier] were also BRAF negative," Kloos and colleagues concluded in the paper. "Similarly, all BRAF-positive specimens were also [Gene Expression Classifier] Suspicious. Neither [Gene Expression Classifier] test sensitivity nor specificity was improved by addition of BRAF mutation testing."

Veracyte offers testing with the Afirma Gene Expression Classifier as part of its comprehensive Afirma Thyroid FNA Analysis, which combines specialized cytopathology assessment with gene expression testing. Veracyte claims that its test can provide doctors with definitive insights about whether a nodule is benign or malignant for thyroid cancer when biopsy results yield inconclusive results. The company estimates that each year as many as 450,000 thyroid nodule FNAs are performed but between 15 percent and 30 percent of these tests are inconclusive. Although in these situations most doctors order thyroid surgery for final diagnosis, up to 80 percent of the nodules end up being benign.

Veracyte is marketing the Afirma Gene Expression Classifier in the US with Sanofi subsidiary Genzyme.

Clinical Validation Study for Allegro's BronchoGen Meets Primary Endpoint

After a clinical validation study met its primary endpoint demonstrating that Allegro Diagnostics' BronchoGen improved lung cancer diagnosis when used in conjunction with bronchoscopy, the company is moving ahead with plans to commercialize the laboratory-developed test this year.

BronchoGen analyzes the gene expression of cytologically normal epithelial cells in the respiratory tract of smokers or former smokers in order to detect early signs of lung cancer.

The prospective, multi-center, case control AEGIS I trial sought to evaluate in 730 patients the ability of BronchoGen plus bronchoscopy to detect lung cancer compared to bronchoscopy alone. Patients enrolled in the trial had to be current or former smokers who were undergoing bronchoscopy because they were suspected of having lung cancer.

"The great results that we have seen from the AEGIS I trial enable us to offer the BronchoGen genomic test as part of routine clinical testing for lung cancer, and we are currently developing our commercial program to make the test available later in 2013 under CLIA regulations," Allegro CEO Michael Webb said in a statement. "We are particularly pleased with the excellent performance of BronchoGen in small lesions and early-stage disease."

The trial sought to establish the sensitivity, specificity, and negative predictive value of BronchoGen to identify patients with lung cancer malignancies. Allegro has not yet announced results from this trial, but has noted that AEGIS I replicated findings from preliminary investigations.

Last year, Allegro reported data that showed that its test combined with bronchoscopy results had a sensitivity of 94 percent compared to a sensitivity of only 74 percent for bronchoscopy alone. Additionally, the negative predictive value for BronchoGen plus bronchoscopy was 28 percent greater than for bronchoscopy alone.

"Allegro is pleased to report that these results were replicated in its clinical validation study and will move forward with commercialization plans," the company said in a statement. Allegro is planning to publish data from AEGIS I in a peer-reviewed journal.

Another study, AEGIS II, enrolled more than 1,300 patients as of July 2012. The final results from this trial are slated for release in the third quarter of this year.

Allegro is hoping to make lung cancer diagnosis more accurate with the help of BronchoGen, since around half of the bronchoscopies performed in the country yield inconclusive results, leading to costly, invasive procedures.

Crescendo Announces Global Launch of MyRA App

Crescendo Bioscience, developer of the Vectra DA molecular diagnostic for rheumatoid arthritis, announced the global availability of a free iPhone app called MyRA to help patients track their disease.

The app, launched in the US in November, is now available for download worldwide, and can run on iPhone, iPad, or iPod touch devices. According to Crescendo, nearly 2,500 people downloaded the app in the first week of its global launch in March.

Developed with the input of both patients and doctors, the MyRA app allows patients to track disease-related symptoms and then integrate these measures into a summary report that they can share with their doctors. The MyRA app is designed to complement the use of tools like Vectra DA. Previously a company official told PGx Reporter that through this app and with the agreement of their doctors, patients can also access their Vectra DA results, drugs they are taking, and at which doses.

Vectra DA, which the company launched in the US in 2010, is multi-biomarker blood test that gauges disease activity in rheumatoid arthritis patients. The test assesses the serum concentrations of 12 immune, endothelial, bone, cartilage, and metabolic biomarkers associated with rheumatoid arthritis and uses an algorithm to generate a disease activity score for a patient between one and 100.

Crescendo believes that the MyRA app will enable patients "to more effectively communicate how they’re doing, which helps doctors to better treat and manage their patients’ RA."