Although the US Food and Drug Administration has yet to review a microRNA-based diagnostic, a Rosetta Genomics official said the clearance of Agendia’s MammaPrint may have bushwhacked a regulatory path that could help Rosetta’s microRNA-based test for cancer of unknown primary.
“If you look at Agendia, they got approval for something based on RNA,” Ron Kamienchick, marketing manager at Rosetta, told RNAi News this week. “So [an miRNA diagnostic] is not introducing something that is completely novel or unfamiliar. We have [many] reasons to be optimistic.”
“We are going to learn from [Agendia and] are in the process of putting the [CUP] program very quickly forward,” added Dalia Cohen, executive vice president and head of research and development at Rosetta. “I believe in 2008 we [could have] a product on the market.”
The FDA approved MammaPrint in February. The test uses an expression signature from 70 genes to help physicians decide whether and how breast cancer will recur.
Rosetta’s optimism extends to its pipeline of miRNA diagnostics, which is led by a test for cancer of unknown primary. Yet the company is being cautious about commercializing its CUP diagnostic, which would represent its first marketed product and put it at the forefront of what is expected to be a lucrative market.
Investment firm CE Unterberg, Towbin last week said that a CUP diagnostic could generate as much as $35 million in revenue for Rosetta in 2011 and reach almost $70 million by 2013, assuming a late-2008 launch.
Kamienchick said that Rosetta has not yet had any contact with the FDA about what it will need to clear the test, noting that “we want to make sure all the lab processes and the test are up to speed, and are being developed right, before we start negotiations” with the agency.
“We’re taking one step at a time,” he said.
One of Rosetta’s next steps is to conduct additional tests of the so-called miRdicator miRNA-detection technology in blinded tumor samples provided by outside sources. This week, the company announced that one of those sources would be the Henry Ford Hospital in Detroit, which will provide Rosetta with samples of metastases found in brain tissue.
In a statement, Rosetta CEO Amir Avniel called the deal “a significant step” to enabling the company to begin clinically validating its CUP test. "The samples we will receive from the Henry Ford Hospital will help validate our lead diagnostic program and advance it forward towards launching the first microRNA-based diagnostic test."
Knowing the Unknown
According to the National Cancer Institute, between 2 percent and 4 percent of all metastatic cancers have an unknown primary, meaning that physicians do not know the source of the metastasis. The prognosis for patients with CUP is “poor,” according to the NCI: Median survival is approximately three to four months, and fewer than 25 percent will live one year with the disease and 10 percent will be alive at 5 years.
“For CUP, a patient is coming to an oncologist with metastases and nothing has been shown to indicate [the cancer’s] origin,” Cohen said. “It’s a long and costly — and sometimes impossible — [process] to identify the origin of the metastases. Basically, the oncologist doesn’t know how to treat the patient, [which is] a very frustrating situation.”
With the growing body of evidence suggesting that specific miRNAs play significant roles in a variety of cancers, Rosetta developed a proprietary process through which RNA, including the miRNA fraction, can be extracted for microarray analysis from fresh, frozen, or formalin-fixed, paraffin-embedded tissue samples.
Agendia “got approval for something based on RNA, so [an miRNA diagnostic] is not introducing something that is completely novel or unfamiliar. We have [many] reasons to be optimistic.”
Recently, Rosetta presented data from experiments in which miRNAs from around 500 fresh and paraffin-embedded cancer tissue samples were extracted and analyzed on a microarray platform containing probes for nearly 700 miRNAs.
About 200 of the tumor samples were classified into 15 different cancer types including bladder, breast, cervix, colon, liver, lung, melanocytes, ovary, pancreas, prostate, small intestine, stromal, testis, thyroid, and uterus. Analyzing the expression of 19 miRNAs, either alone or in specific combinations, the company was able to classify the tumor type of each sample with around 85-percent accuracy.
Based on the success of this work, Rosetta will conduct additional testing of its miRdicator technology in blinded tumor samples, including ones provided under its deal with the Henry Ford Hospital.
"Our CUP diagnostic program has been showing rapid progress over the past few months," Cohen said in a statement. "We are continually expanding the test, and believe we have reached a point where we can confidently begin running blind samples of metastases on our [detection] platform to identify their origin."
According to the CE Unterberg, Towbin report, Rosetta is also expected to strike a similar deal with another tumor sample provider as part of the company’s effort to expand the number of miRNAs associated with tumor origin and boost the efficacy of the CUP diagnostic.
Cohen noted that Rosetta is also likely to forge a partnership with a laboratory that will run the CUP diagnostic assays while Rosetta builds the infrastructure required to do so itself.
Getting approval to conduct the assays for clinical applications is a long process, Cohen said. “We are [moving] forward with our CUP project and we don’t want to wait for all the processes needed for an approval internally” before getting the product onto the market.
“Probably in the future, we will build [these capabilities] internally,” she added.