Axonyx Announces Positive Phase II Results for Phenserine in Alzheimer's Disease.

Health/Medical Writers

NEW YORK--(BW HealthWire)--Oct. 30, 2001

Phase II clinical trial reveals excellent safety profile

as well as improvement in memory and cognition

Axonyx (NASDAQ: AXYX) today announced positive safety and efficacy results from its Phase II Proof of Concept clinical study of Phenserine, its lead acetylcholinesterase inhibitor, for the treatment of Alzheimer's Disease (AD).

The safety results from the 72 patient Phase II clinical trial of Phenserine in mild to moderate AD patients substantiates that the drug is safe and well tolerated. The incidence of adverse events reported during the 12-week treatment period was on average less than that reported for currently marketed products in the same drug class. Specifically, nausea and vomiting associated with Phenserine treatment was infrequent, i.e. at a level of 8.5% or less.

While primarily designed for safety, the results of the clinical trial also revealed positive efficacy data. Statistically significant (p= 0.05) efficacy was achieved in two of the key pre-defined secondary efficacy endpoints: the Maze test of the extended ADAS-cog (a measure of executive function) and the CANTAB-PAL test (a measure of memory). The Intention to Treat analysis of the CANTAB-PAL also showed statistically significant improvement (p< 0.05) of Phenserine treated patients versus placebo treated patients. CANTAB has been shown in more than 150 peer-reviewed publications to be a sensitive and reliable tool for the measurement of drug and disease effects on cognition and psychological function.

There is abundant evidence that executive dysfunction, as measured by worsening of the ADAS-cog Maze test is associated with the onset and progression of AD. The primary efficacy endpoint of this clinical trial, as in most AD clinical trials, was the ADAS-cog test. Based on a predefined statistical analysis of the placebo and treated patients in this clinical study, the ADAS-cog test showed a p=0.147. Based on these encouraging clinical results, Axonyx believes that a Phase III development program is warranted.

"Based on the current analysis, we are very encouraged and confident that Phenserine can become a drug of choice in the worldwide multi-billion dollar Alzheimer's Disease market," said Marvin S. Hausman M.D., Chief Executive Officer of Axonyx. "The results clearly suggest that Phenserine is at least as safe and well tolerated as currently marketed products and, in a clinical trial not designed to reveal clinical efficacy, our drug improved memory and cognition in mild to moderate AD patients."

About the Clinical Trial

Five clinical sites in the United States, experienced in the conduct of AD clinical trials, participated in the Phenserine Phase II clinical trial. Prior to enrollment in the clinical trial, all patients were assessed in order to determine the extent and severity of their Alzheimer's Disease as well as to record any other ongoing medical conditions and/or medications. A total of 72 mild to moderate eligible AD patients were randomized to a double blind, placebo-controlled clinical trial; two thirds (48) of these patients received Phenserine 5 mg twice daily for two weeks, followed by Phenserine 10 mg twice daily for 10 weeks, the remaining one-third (24) of patients received placebo for 12 weeks. All patients then continued in a further four week washout period.

During the course of the clinical trial, physicians and nurses regularly evaluated all patients. Side effects, if any, and changes in the severity of the patients' Alzheimer's Disease, as measured by a variety of memory and cognition tests, were recorded.

Positive Clinical Trial Results

The adverse events reported during the course of the trial were within the profile of the acetylcholinesterase inhibitor drug class. Of particular note was the low incidence of side effects associated with the digestive tract, i.e. nausea (8.5%) and vomiting (2.1%). Dizziness, reported by 8 out of 47 (17.0%) patients taking Phenserine 10mg twice daily, was the side effect reported most often. All other adverse events were reported in less than 8.5% of cases and were considered mild in nature. These adverse events were not reported in the patient group treated with placebo.

The clinical trial was primarily conducted to assess the safety and tolerability of Phenserine. It was not powered, i.e. the trial did not include the number of patients required, to detect clinical improvement in efficacy as measured by the ADAS-cog at a statistically significant level. The ADAS-cog is a recognized memory and cognition test widely used to measure the degree of cognitive change in Alzheimer's Disease clinical trials. The results on the extended ADAS-cog (which includes the Numbers Cancellation test, the Maze Test and the delayed word list recall) suggest, following a per protocol analysis (where n=54), an improvement in memory and cognition as a result of Phenserine treatment (ADAS-cog: 2.556-point improvement from baseline with Phenserine, 0.722-point improvement for placebo). In the ADAS-cog Maze test (total seconds to complete), which measures executive function, patients improved significantly (non-parametric Wilcoxon-Mann/Whitney; p=0.034). There is abundant evidence that executive dysfunction is associated with the onset and progression of AD.

In addition, use was made of the Cambridge Neuropsychological Test Automated Battery (CANTAB). CANTAB has been shown in more than 150 peer-reviewed publications to be a sensitive and reliable tool for the measurement of drug and disease effects on cognition and psychological function. Specifically, the Paired Associates Learning (PAL) test in CANTAB showed a statistically significant improvement on Phenserine in both the per protocol analysis (two-tailed t test; p= 0.045) as well as in the Intention to Treat analysis (two-tailed t test; p< 0.05). The results of other efficacy tests were not statistically significant.

"These clinical data on Phenserine are clearly encouraging. Phenserine shows potential advantages over currently approved cholinesterase inhibitors and the Phase III program will be designed to substantiate these clinical benefits," said Dr. Steven Ferris, Director of The Alzheimer's Disease Center at NYU School of Medicine and a member of Axonyx's Scientific Advisory Board.

"Although we were blinded as to what individual patients were receiving during the trial, physicians and research coordinators alike were impressed as to how few side effects were being reported by patients and caregivers," said Larry Eisner, M.D. one of the Principal Investigators in the clinical trial.

"The combined strength of these results, as well as Phenserine's potential ability to slow disease progression, more than justifies the continued development of Phenserine. We will now work towards finalizing the Phase III clinical trial designs," said Gosse B. Bruinsma MD, Chief Operating Officer of Axonyx Inc. "We will also continue to explore opportunities for corporate partnerships and licensing agreements with the goal of accelerating the development of Phenserine and optimizing potential marketing opportunities," he added.

Axonyx will host a conference call on Tuesday, October 30th at 11:00 a.m. EST. The conference call will be open to all interested parties through a real-time audio web broadcast at the Axonyx corporate web site, http://www.AXONYX.com. Interested parties may also participate in the teleconference by calling 1-800-388-8975 fifteen minutes before the conference begins and ask to be connected to the Axonyx teleconference. International callers please dial 1-973-694-2225.

About Alzheimer's Disease

Alzheimer's Disease affects 12 million people worldwide with the numbers expected to continue to rise. Characteristics of Alzheimer's Disease include dementia and relentless, irreversible brain degeneration leading to memory loss, impaired judgment, difficulty expressing oneself through speech, the inability to work and eventually death. These characteristics of Alzheimer's are caused by a progressive loss of nerve cells in the brain, particularly in areas associated with memory and learning. The cost to society in the USA alone has been estimated to be approximately $100 billion per year.

About Phenserine

Phenserine is Axonyx's lead compound in development for the treatment of Alzheimer's Disease. Phenserine is a potent and selective inhibitor of acetylcholinesterase, an enzyme that breaks down an important neurotransmitter in the brain involved in memory and cognition. Phenserine has been shown in in vitro studies to have the additional ability to inhibit the formation of beta-amyloid precursor protein (Beta-APP) [Proc Nat'l Acad Sci USA. 2001 Jun19:98(13):7605-10]. Beta-APP is thought to be the precursor to beta-amyloid, the toxic protein laid down in plaques around nerve cells causing their death.

About Axonyx

Axonyx Inc. is a United States based biopharmaceutical company engaged in the acquisition and development of proprietary pharmaceutical compounds and new technologies useful in the diagnosis and treatment of Alzheimer's Disease, human memory disorders, and prion-based illnesses such as Mad Cow Disease.

This press release may contain forward-looking statements or predictions. These statements represent our judgment of this date and are subject to risks and uncertainties that could materially affect the Company including those risks and uncertainties described in the documents Axonyx files from time to time with the Securities and Exchange Commission, specifically Axonyx's Annual Report on Form 10-KSB, as amended. The results reported here are preliminary and based on a trial with a small number of patients. Axonyx cannot assure that future clinical trials, if any, with Phenserine will prove successful, that the safety and efficacy profile of Phenserine exhibited in this small Phase II trial will remain the same in much larger Phase III trials, that Axonyx will obtain the necessary financing to complete Phase III Phenserine trials, that the Company's development work on Phenserine will support an NDA filing, that the FDA will grant marketing approval for Phenserine, that the FDA will approve the protocol for a Phase III trial, that the results of the Phase III trials will allow Phenserine to be approved by the FDA, that if Phenserine is approved by the FDA, it will prove competitive in the market, and that Axonyx will obtain licensing or corporate partnership agreements that will enable acceleration of the development of and optimize marketing opportunities for, Phenserine. Axonyx undertakes no obligation to publicly release the results of any revisions to such forward-looking statements that may be made to reflect events or circumstances after the date hereof or to reflect the occurrence of unanticipated events.