The headline for this story has been updated from a previous version to clarify that the company has completed enrollment for the trial.
Allegro Diagnostics announced last week that it has completed enrollment of a trial it hopes will provide additional validation of its BronchoGen lung cancer diagnostic ahead of a launch early next year, as well as provide clinical utility data to support future reimbursement discussions.
BronchoGen is a gene expression classifier that Allegro plans to market as a rule-out test to help physicians decide whether their patients with a history of smoking have lung cancer when bronchoscopy yields inconclusive results.
Mike Webb, Allegro's president and chief executive officer, told PGx Reporter that the test is designed to be an adjunct to bronchoscopy, which is a method of investigating the lungs of patients for suspicious lesions.
The BronchoGen test analyzes samples of the normal epithelial cells lining the lungs and gauges the expression of about 30 genes. Pulmonologists who plan to use the test would take additional samples from patients during bronchoscopy. In the case of indeterminate findings, doctors would submit these additional samples for testing with BronchoGen. The test will most likely stratify patients into three risk groups, similar to Genomic Health's Oncotype DX test for breast cancer risk, according to Webb.
"The idea is that a pulmonologist diagnosing patients will reflex to BronchoGen when they can't get a definitive result from a routine bronchoscopy procedure," Webb said.
He estimated that between 50 percent and 60 percent of bronchoscopies yield indeterminate results. As such, in this uncertain setting, doctors are in need of tools to help them discern whether to recommend patients for more invasive diagnostic procedures, such as needle biopsy, or to take a watch-and-wait strategy, which consists of routine CT scans over a 12-month to 18-month period.
"What we're trying to do is avoid sending the wrong people down the invasive pathway. There are a lot of cost savings to be had there," Duncan Whitney, Allegro's senior vice president of research, development, and technical operations, told PGx Reporter.
Based on economic modeling of the cost savings conferred by avoiding future procedures for low-risk patients, the company expects to have a list price for the test in the range of $3,000.
Webb estimated that there are about 300,000 bronchoscopies performed every year in the US for suspected lung cancer, and about half of them yield indeterminate results. The company's initial target market for BronchoGen would be those 150,000 patients per year who receive inconclusive results.
According to Webb and Whitney, the company's ongoing prospective, multi-center trial, called AEGIS II, will analyze about 1,400 samples to compare the predictive ability of BronchoGen plus bronchoscopy to bronchoscopy alone.
The study follows on a previous trial, AEGIS I, which looked at 700 patient samples. Webb said the company is hoping the two studies will confirm its target negative predictive value for the test of more than 85 percent.
"The goal that we have is to be able to show that BronchoGen in combination with bronchoscopy offers better overall accuracy compared to bronchoscopy alone," Whitney said.
"[For the] standard of care with bronchoscopy, typically what we see is a negative predictive value in the 60 percent range," he said. Allegro is hoping that by adding the BronchoGen score it can improve the negative predictive value of the combination diagnostic method to over 85 percent.
"There are some basic issues with the indeterminate rate [of bronchoscopy]," he explained. "So what we [hope to] indicate to pulmonologists is … if they can get the lesion of interest and everything looks OK, [that's] great. There may be no need for our test."
The gene expression signature at the heart of the BronchoGen test is based on work by two Boston University researchers, Jerome Brody and Avrum Spira, who now serve as advisors to Allegro.
Originally, Whitney said, the BU team described an 80-gene signature. Allegro, in its development work, has narrowed the original gene set down to about 30 genes and has converted the test technology from microarrays to PCR assays.
The company ultimately plans to report BronchoGen results with three risk ranges: low risk, intermediate risk, and high risk.
"In our case, we would define [the risk categories] whereby doing so, not all of the patients then fall into either low or high … [so that] the performance of the test improves significantly for the low risk group, where you want to rule out cancer," Whitney said.
Webb and Whitney further explained in an e-mail to PGx Reporter that patients who fall into the low-risk category with BronchoGen testing will be defined as having a high negative probability of cancer. So, for these patients pulmonologists would have more confidence recommending a watch-and-wait strategy. Meanwhile, patients determined to be at high risk by BronchoGen will be defined as having a high positive probability of cancer, which may provide doctors greater confidence in prescribing follow-on procedures.
According to Whitney, the company is in the midst of conducting its final analytical and clinical validation of the PCR-based test in its CLIA-certified laboratory using patient samples from the AEGIS I study. With AEGIS II, Allegro hopes to add "even greater evidence and an independent set of samples for the validation of the signature."
"With regulating bodies and on the reimbursement side, it's really important to be able to offer secondary trials and studies to demonstrate that the test is reproducible and that there is clinical utility. That's the primary goal of the trial," Whitney added.
Allegro is planning to launch BronchoGen as a lab-developed test through its CLIA lab. Allegro intends to release data from AEGIS I later this year and data from AEGIS II in 2013. According to Webb, the company will be ready to launch the test in the first quarter of next year.
"We are going to be working ... during 2013 to put together a dossier of evidence for reimbursement for Medicare," he added. "We believe that [with] the results from AEGIS II … we'll have a very compelling clinical validation and utility package that we can take to Medicare at the end of the year."
At the same time, Whitney said the company is also working on other tests for improving lung cancer diagnosis.
One active research area, he said, is the development of a lung cancer screening test that uses the same method of gene expression measurement in epithelial cells as the BronchoGen test, but rather than sampling from the lungs, this non-invasive test would sample from the nasal epithelium.
Whitney said the basis for this work also comes out of BU, and has more recently been taken up by Allegro. The company is planning to embark on a discovery program for the test they are calling "NasoGen," using nasal samples collected as part of the AEGIS trials.
Additionally, Whitney said, the company is also looking into applying similar diagnostic principles to develop a test for chronic obstructive pulmonary disease.