Phenserine Phase III Studies Proceed After Alzheimer’s Drug Fails Pivotal Trial
This article was originally published in Pharmaceutical Approvals Monthly
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Axonyx' investigational Alzheimer's agent phenserine failed to show significance for either co-primary endpoint in a Phase III trial, the firm said Feb. 7. Although phenserine showed some benefit in standard Alzheimer's cognitive (ADAS-cog) and memory (CIBIC) assessments after 26 weeks, "the outcome was potentially confounded by a better than expected ADAS-cog response in placebo-treated patients," Axonyx said. Study data were not released, but Axonyx reported there were no safety or tolerability issues. The company previously projected NDA submission for mild to moderate AD in the 2006/2007 timeframe. Axonyx plans to continue phenserine's development, with two other pivotal studies underway. The identical placebo-controlled Phase III trials, initiated in June and September 2004, will enroll a larger patient population (450 AD patients with mild to moderate disease, compared to 384 in the failed trial). Axonyx is also conducting trials to further characterize phenserine's mechanism of action. A Phase IIb study is evaluating phenserine's ability to lower beta-amyloid precursor protein and beta-amyloid in plasma and cerebrospinal fluid (CSF). The failed Phase III study "will not impact the interim analysis planned of the available CSF and plasma samples for beta-APP and beta-amyloid, and these results are expected before the end of March," the company said. Data from the failed study will be used "to optimize the trial designs in the currently planned program," Axonyx said. Phenserine has been touted as potentially the first novel disease-modifying AD agent that will be filed at FDA. Like other AD therapies, phenserine is an acetylcholinesterase inhibitor, but "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 beta-amyloid," Axonyx said. New York-based Axonyx' stock fell 62.5% - from $3.02 to $1.81 - following the firm's Feb. 7 announcement. |