Anthrax Vaccine Trial Of 1,500 Patients Could Begin In Summer 2000

An anthrax vaccine study involving 1,500 patients could begin as early as this summer.

The trial is expected to study changes in the dosing regimen, changes to the route of administration and gender differences in the safety and efficacy of the vaccine, known as Anthrax Vaccine Adsorbed.

The Centers for Disease Control, National Institutes of Health and Department of Defense are collaborating to study the safety and efficacy of the vaccine with $20 mil. transferred from NIH to CDC under the fiscal year 2000 appropriations bill (¹ (Also see "DoD Investigational Drug Testing Policy Expected By Early Next Year" - Pink Sheet, 29 Nov, 1999.)).

In addition to the human trials, an immunogenicity study will be conducted in animals to "determine the amounts of immunity that are built up and whether we really need an annual booster," Special Assistant to the Secretary of Defense Major General Randy West said during a Feb. 17 DoD press briefing.

Following discussions with FDA to determine what data would be sufficient to support labeling changes, the collaborating agencies are finalizing study protocols.

The study could lead to a reduction in the dosing schedule by eliminating the second of six doses and a change in route of administration from subcutaneous to intramuscular, which is expected to reduce injection site reactions.

Funds have also been set aside for development of a recombinant protective antigen vaccine, which an NIH working group has agreed is the most promising second-generation candidate to replace the current vaccine (² (Also see "Anthrax Vaccine Product May Be Studied By DoD; Facility Being Renovated" - Pink Sheet, 3 May, 1999.)).

General West emphasized that the FDA approved immunization program should continue "until we've got a new and improved vaccine" which he claimed "is a long ways away." DoD is "very confident" in the anthrax program and has no plans to change the program, DoD officials said.

West's remarks responded to a House Government Reform/National Security, Veterans Affairs & International Affairs Subcommittee report released Feb. 17 calling for a temporary suspension of the Anthrax Vaccine Immunization Program, begun in March 1998, under which DoD plans to vaccinate 2.4 mil. personnel on active and reserve duty. The report was prepared by the Government Reform/National Security Subcommittee's Republican staff.

To date, FDA's Vaccine Adverse Event Reporting System has received 620 reports related to AVA, of which 70 were considered caused by the vaccine, according to DoD.

The subcommittee report expresses concern over the efficacy of the vaccine against biological warfare and found the program to be "a well-intentioned but over-broad response to the anthrax threat" which is "vulnerable to supply shortages and price increases" and "logistically too complex to succeed."

The report states that military personnel inoculated with anthrax vaccine adsorbed should be considered study subjects and that the current vaccine use in military personnel be treated as an IND.

"Administration of the anthrax vaccine for mass prophylaxis against biological warfare should be considered an off-label use of the product to treat an indication for which it is not explicitly licensed," the report states.

"Both the new indication and the new schedule should be undertaken only pursuant to FDA regulations governing clinical trials of investigational new drugs."

If AVA were considered an IND under FDA's jurisdiction, "DoD would be required to inform vaccine recipients adequately, obtain informed consent and gather data on vaccine safety consistently," the report explains. It adds that "DoD could request the President waive the informed consent requirement for certain deployed personnel."

The report also called for a "comprehensive clinical evaluation and treatment program for long-term study" including all those who have received the vaccine.

The full Government Reform Committee will mark-up the anthrax report March 2.

Concerns over anthrax protection for the military could extend to the civilian population as CDC builds the National Pharmaceutical Stockpile to counter threats of bioterrorism, including anthrax attacks.

The Department of Veterans Affairs manages existing domestic federal stockpiles for HHS' Office of Emergency Preparedness, and the Marine Corps Chemical Biological Incident Response Force keeps medical supplies.

CDC is building the national pharmaceutical stockpile and has received over $50 mil. during each of the last two years for establishing the stockpile. The fiscal year 2001 budget requests $52 mil. for the stockpile (³ (Also see "Vaccine Tax Credit In Clinton Budget Is Based On Sales To Nonprofit Groups" - Pink Sheet, 14 Feb, 2000.)). CDC has selected VA to manage the national stockpile of pharmaceuticals and vaccines.

A recent General Accounting Office Report found "poor management controls and the lack of required items" to respond to a biological or chemical terrorist attack. GAO noted a 12% discrepancy between the OEP's required list and the actual OEP stockpile.

The report cautions that CDC's "current plan does not include comprehensive internal controls to prevent the types of problems found at the other agencies."

GAO warns that CDC's draft plan for the stockpile program does not include information on how CDC will review and assess the stockpile and the VA, the security measures CDC will have to safeguard the stockpile and the specific personnel responsibilities for organizing and overseeing the stockpile.

The HHS response to the GAO report notes that CDC "has found GAO's insights very helpful" as the agency develops the stockpile and an agreement with the VA. CDC plans to have the VA begin stockpiling items 14 days after the interagency agreement is signed, the report states.

The GAO report will be discussed at a March 8 hearing of the House Government Reform/National Security, Veterans Affairs & International Relations Subcommittee. Witnesses will include GAO Associate Director-Veterans Affairs & Military Health Care Issues Cynthia Bascetta, CDC National Center for Infectious Disease Director James Hughes, MD, and VA Acting Deputy Undersecretary for Health Francis Murphy, MD. Representatives from OEP and DoD are also expected to testify.