Medical Device Daily

Large companies can roll with the punches delivered by the FDA. Delivered against small companies, these punches are potential knock-out blows.

After receiving a non-substantially equivalent letter from the FDA last month for its skin cholesterol test, Prevu, PreMD (Toronto) has now filed a request for a second level review of the 510(k) submission.

“It’s been devastating in terms of impact on the company,” Brent Norton, president/CEO told Medical Device Daily, later acknowledging that the decision puts the company in “a tough spot.”

“The market value of the company has fallen through the floor. We’ve taken all the action we can to reduce costs, including laying off one-third of the workforce. We’re a small company, so that’s just six people.”

PreMD was seeking an expanded regulatory claim on its point-of-care skin cholesterol test — a non-invasive assay measuring the amount of cholesterol accumulated in the skin tissues — suggesting that it would cost no more than a blood test for LDL levels. Such an assay also could be used as an indicator of coronary artery disease, cerebrovascular disease or peripheral artery disease in patients with no known symptoms.

Norton said the FDA’s primary reason for rejecting the claim relates to the clinical utility of evaluating skin cholesterol, with carotid wall intima thickness as the clinical endpoint.

PreMD submitted the 510(k) application to the FDA in June 2007, based on a study design previously accepted as appropriate by the FDA.

The FDA then requested additional information regarding statistical clarification on the data submitted (MDD, Sept. 10, 2007) — not an unusual request on the FDA’s part, but companies frequently calling this a rule change in mid-stream.

PreMD provided the information asked for and, Norton said he believes that the company adequately addressed those concerns.

Approval of the broader claim would have made Prevu the first “cost-effective” (in the $10 to $20 range), non-invasive test on the market, according to the company.

In light of the non-equivalent ruling by the agency, PreMD implemented the workforce reduction and other decreases in general and administrative expenses. The remaining key members of PreMD are concentrating their efforts on the FDA review and assessing alternatives.

“We have enough cash to meet short-term goals for the next few months,” Norton said, adding that the company is considering all options to stay afloat — from fund-raising to a possible merger. “There still is significant value to what we have going here, but we’re in a tough spot.”

PreMD says it is continuing to advance development programs for other product candidates in its oncology pipeline.

The company’s other skin cholesterol products include Prevu(x) LT, a test designed for use in the life insurance industry. The company’s cancer tests include ColorectAlert, LungAlert and a breast cancer test.

The company says it is working with AstraZeneca Pharmaceuticals (Phoenix), which licensed the Prevu test for marketing and distribution in the U.S., to fully explore the issues raised by the FDA and address the appropriate steps going forward.

Prevu is already cleared in the U.S., Canada and Europe for those considered at risk for heart disease, including people with symptoms such as high blood pressure, high cholesterol, diabetes or smoking.

Late last year, the company issued a report at the annual meeting of the American Heart Association (Dallas) that Prevu demonstrated the ability to detect risk of cardiovascular disease in asymptomatic subjects.

This study marked the largest clinical trial to date to evaluate levels of skin cholesterol in asymptomatic individuals, the company said. Titled, “Increased Skin Cholesterol Identifies Individuals at Increased Cardiovascular Risk: The Predictor of Advanced Subclinical Atherosclerosis (PASA) Study,” the company said that the study supports the usefulness of non-invasive skin cholesterol measurements for cardiovascular disease risk assessment.

Results of the PASA Study showed that skin cholesterol content, measured by the test, was associated with carotid intima-media thickness (CIMT) and the presence of carotid plaque. This association was observed in subjects across all ranges of cardiovascular risk, particularly in those at low and intermediate risk, based on traditional cardiovascular risk factors.

CIMT and carotid plaque are both well-established markers for risk of future heart attack and stroke, according to the company.

PreMD’s other skin cholesterol products include PREVU(x) LT, a test designed for use in the life insurance industry.