Hoping to back up the positive data yielded from a Phase II trial, Axonyx Inc. began a Phase III trial in Europe of its Alzheimer's disease drug Phenserine, an acetylcholinesterase and beta-amyloid peptide inhibitor.
"This is pretty exciting," said Matt Kaplan, analyst with Punk, Ziegel & Co. in New York. "It's a new drug that could have an impact on disease progression."
Several existing acetylcholinesterase inhibitors address the symptoms and can improve short-term memory, but do not slow the disease, he added.
The randomized, placebo-controlled, double-blind trial will evaluate the safety and efficacy of two different doses of Phenserine in 375 mild to moderate Alzheimer's disease patients for six months. Improvements will be measured with standard memory and cognition tests.
Also under way is a Phase IIb study designed to evaluate Phenserine's ability to lower the levels of the beta-amyloid precursor protein and beta-amyloid in the plasma and cerebrospinal fluid of mild to moderate AD patients.
In the brain, toxic beta-amyloid is viewed as a key pathological event in the cause and advance of the disease. The company plans to fold the 75 patients from the Phase IIb study into the potentially pivotal Phase III trial.
Of all the available drugs, Aricept (donepezil hydrochloride) probably is the most prescribed, Kaplan said. Aricept buys time and relieves some symptoms, but it has gastrointestinal side effects that Phenserine has been shown not to have.
Developed by New York-based Pfizer Inc. and Eisai America Inc., which is part of Tokyo-based Eisai Co. Ltd., Aricept was approved in the U.S. in 1996. Kaplan said it has "the best side effect profile out there," but about 10 percent of Aricept patients experience nausea and vomiting.
The other marketed Alzheimer's drugs are Reminyl (galantamine HBr) from Janssen Pharmaceuticals NV, of Beerse, Belgium, approved by the FDA in 2001, and Exelon (rivastigmine tartrate), from Novartis Pharmaceuticals Corp., of East Hanover, N.J., approved in 2000.
Reminyl, approved in February 2001, sold about $130 million in the second half of that year and last year sold $250 million, even with a side effect profile worse than Aricept's (though not as bad as Exelon's).
New York-based Axonyx's Phenserine, viewed solely from a "me-too point of view," would likely do better because of its lack of side effects, Kaplan told BioWorld Today.
"If you look at the Phase II data from Phenserine, it has as good or better side effect profile," he said. "[The trial] wasn't head to head, so you can't definitively say it was better or worse, but it looks to be in the ballpark. It looks like [Phenserine] can come in and minimally do something like Reminyl did, probably a little better."
Patients "typically cycle through these drugs, and if your grandmother is failing on Aricept, you're going to try something else," he said - and something with fewer side effects is the naturally better candidate.
"What we're basing our analysis on is the Phase II study, and it looks like [Phenserine] is clearly active and having an impact on memory and cognition," as well as causing less nausea, he said.
"But the wild card is its second mechanism of action," Kaplan said - that being the inhibition of beta-amyloid, which has been shown to "strangle neurons" and, if blocked, could mean a slowing of the disease.
The company has made no public estimate on when the Phase III trial will finish, but Kaplan predicted data would be available late next year or early in 2005, adding that results could arrive sooner or later than that.
"It's all enrollment driven," he said.
Meanwhile, Axonyx will be looking for a partner. The company consists of only four people, with a contract research organization hired to help Gosse Bruinsma, Axonyx's chief operating officer, conduct the Phase III trial. The trial will start after the conclusion of the steering committee and investors' meeting, held today and Saturday in Munich, Germany.
As the product has advanced, risk has lessened and would-be partners are showing more interest in a marketing deal, the company said.
Axonyx officials could not be reached for comment.
Axonyx's stock (NASDAQ:AXYX) closed Thursday at $2.09, down 30 cents.