The Dundee-based company applied for permission in February 2009 for one of its diabetes testing kits to be used by non-doctors to test patients.
The US Food and Drug Administration (FDA) has now denied permission, although the test will continue to be used by medical personnel.
Axis-Shield's management team had consistently said that the outcome of the application was always uncertain.
No other applications for the use of similar tests have ever been granted by the FDA
The FDA has requested further data, which the company said it would submit as soon as it becomes available.
The company's Afinion ACR diabetes test went on sale in America in February 2008 for use by doctors.
The test is used to assess a patient's urine to measure their kidney functions and any heart and lung complications, which can happen with patients who have poorly-controlled diabetes.
Chief executive Ian Gilham said he was "disappointed with the current outcome" but highlighted that the market for ACR testing in diabetes is "relatively small" compared with the growing market for another test for the disease that the company already sells.
Shares closed down 1.3 per cent or -3.5p at 260p.