No significant efficacy in PIII Alzheimer's trial

A Phase III clinical trial with Phenserine, in development for mild to moderate Alzheimer's disease (AD), showed that although there were encouraging trends with both Phenserine 10mg and 15mg twice daily, overall these did not result in a statistically significant improvement over placebo for the protocol's primary endpoints following 26 weeks of treatment.

While Phenserine-treated patients performed better in the ADAS-cog and CIBIC assessments, the study's primary endpoints, at almost all time points, the outcome was potentially confounded by a better than expected ADAS-cog response in the placebo-treated patients. A preliminary review of the adverse events has revealed no safety or tolerability concerns associated with Phenserine treatment. Axonyx, the US biotech company carrying out the trials, is continuing to further analyse the data and says it will use this information to optimise the trial designs in the currently planned program.

However, Dr Elemer Piros, an analyst at New York-based Rodman & Renshaw Equity Research, suggested that: 'based on a number of positive signs, the drug should be further developed.' He suggested that: 'testing the drug for a longer period of time (>=52 weeks vs. 26 weeks), having patients that are documented "decliners" on existing therapy should theoretically maximise the chance to see significant efficacy.' Piros also suggested that increasing the proportion of patients on placebo and avoiding regions notorious for placebo effects could alleviate high placebo responses (lack of cognitive decline) and amplify the signal. 'There's no need to test the lower dose arm (10mg BID) any further, which in itself would increase the proportion of placebo patients. Finally, increase the power of detecting the signal by increasing the sample size (>>375 patients).'

The Phase III trial recruited 384 mild to moderate Alzheimer's patients from 16 clinical sites in Spain, United Kingdom, Croatia, and Austria. Patients, after being diagnosed as having probable AD, were randomised to receive placebo, Phenserine 10mg twice daily or 15mg twice daily for a period of six months. Throughout the treatment period patients were regularly assessed using standard cognition and memory assessments.

AD and Phenserine

Phenserine is currently undergoing testing in a Phase IIB trial to evaluate its anticipated ability to lower levels of beta-amyloid precursor protein (ß-APP) and beta-amyloid (Aß) in the plasma and cerebrospinal fluid (CSF), which may lead to a slowing of disease progression. The results of the Phase III trial will not impact the interim analysis planned of the available CSF and plasma samples for ß-APP and Aß, and these results are expected before the end of March. Phenserine is a highly selective acetylcholinesterase (AChE) inhibitor that breaks down a neurotransmitter in the brain important in memory and cognition. Unlike other AChE inhibitors, which only suppress the activity of the enzyme, Phenserine has been shown to have two mechanisms of action: (1) the inhibition of the AChE enzyme, and (2) in preclinical studies, the inhibition of the synthesis of Aß, the protein in the brain that is thought to be a cause of brain cell death in Alzheimer's disease.