AEGiS-GMHC: FDA Panel Takes Up Viral Load

Important note: Information in this article was accurate in 1996. The state of the art may have changed since the publication date.

FDA Panel Takes Up Viral Load

GMHC Treatment Issues, Vol. 10, No. 3 - March 1996
Theo Smart

Here is yet another FDA action taken as the March Treatment Issues went to press: the agency's Blood Products Advisory Committee on March 21 reviewed an application for approval of Roche Molecular System's "Amplicor HIV Monitor." This assay measures HIV RNA (viral load) in plasma. The committee appeared dumbfounded as it was given only five hours to digest a large body of data presented by the sponsor, the FDA, outside experts, and representatives from companies with competing products.

Roche is seeking approval of the test "in combination with clinical presentation and other laboratory markers such as CD4 cell counts," said Roche's John Sninsky, Ph.D. Amplicor's several anticipated uses include: "as an indicator of disease prognosis; as an aid in monitoring the effects of antiviral therapy on plasma RNA levels; and as a predictive marker for clinical endpoints in HIV infected individuals." To support the indication, data was presented from several studies of nucleoside analogues and protease inhibitors as well as data from observational cohorts such as the MACS study (see Treatment Issues, November, 1994, pages 4-6, 10-11 and January, 1996, pages 13-14).

The data indicated that: 1) high viral loads were predictive of more rapid progression to disease and death; 2) viral load can show whether a drug has antiviral activity within a week of initiating treatment; and 3) short-term rises or drops in viral load were correlated with eventual changes in health status.

But the lack of uniformity across the studies (which used different viral load tests and different methods for storing the blood) made it difficult to the determine absolute values or standards needed for using the Amplicor to manage individual patients. The studies presented to the committee were not designed to decide at what viral load treatment should begin in the average patient, nor how great an increase in viral load should trigger a switch in treatment.

Roche has never sponsored such studies and apparently expected that the answers could be inferred from the large drug trials, which do show general trends. As the advisory panel's outside consultant Douglas Mayers, M.D., observed, the problem for the clinician remains, "what do you use for your yardstick?"

The purpose of the advisory meeting, according to Curtis Scribner, M.D., Deputy Director of the FDA's Office of Blood Research and Review, was only to "ask the scientific experts for their opinions on the data supporting the test's possible indications, and what should be the post-marketing requirements for the sponsor."

In the end, the advisory panel didn't take a formal vote. It is unclear what the FDA will make of the deliberations as several members admitted to being "overwhelmed by the data." Charles Flynn, M.D., of the committee acknowledged that "this test measures what it claims to measure," but felt that the sponsor should provide "better data that gives us algorithms for how to use this test." Chairman Scott Swisher, M.D., summed up his group's sense that the "test does have some prognostic value, and does have some value for showing whether a drug is having an antiviral effect," but "on the other hand, I felt completely uninformed about how I would use this test in my clinical practice."

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