By Starr, Cynthia
Drug Topics , Vol. 135, No. 16
Late last month, the Food & Drug Administration and Warner-Lambert Co. were occupying opposite ends of a wobbly seesaw. The fate of a compound that has been expected to become the first available drug for the treatment of Alzheimer's disease depends on the riders' ability to strike a balance.
An agent called tacrine or Cognex (also known as tetrahydroaminoacridine or THA) provides the fulcrum upon which the two sides are teetering. The drug candidate is designed to boost levels of acetylcholine, a neurotransmitter known to be deficient in Alzheimer's patients.
This past March, members of the FDA's Peripheral and Central Nervous System Drugs Advisory Committee voted that the company's efficacy data did not yet warrant approval of the drug. At a second meeting in July, the committee held firm to that original stance. However, the eight-member voting panel was then asked to consider whether W-L should have a Treatment IND.
Try again: "The majority of the group, as I recall, said they thought the company should do another efficacy trial--a controlled efficacy trial at a higher dose of 120 mg," FDA spokeswoman Faye Peterson told Drug Topics. Patients had previously been treated with 40- and 80-mg doses per day of tacrine.
As for the Treatment IND, Peterson said, the panel was "a little split." Because the drug demonstrated a potential for liver damage when given at higher doses in earlier trials, the company would have to closely monitor patients if W-L were given permission for a Treatment IND, she added.
Most of the experts, Peterson went on, agreed that if the company could fully enroll an efficacy trial and get it under way, it could also receive a limited Treatment IND. The safety data culled from patients receiving the drug outside of the controlled study could be used in the application for marketing approval.
"We hadn't sought to do another (efficacy) trial," noted Peter Wolf, W-L manager of media relations. Instead, he said, the drugmaker was hoping that making tacrine available to a large number of patients through a Treatment IND would allow researchers to gather more information confirming its safety.
Reversible effect: The clinicians who have studied the drug believe the elevations that occur in liver enzymes are manageable and reversible, Wolf said. "We're not saying you don't need to be concerned. …