Posiphen Treatment Provides Clinical Improvement of Alzheimer and Parkinson Disease in Clinical Trials

In phase 1 and 2 studies (NCT04524351), respectively, people with early Alzheimer disease (AD) and early Parkinson disease (PD) who were treated with posiphen (ANVS401; Annovis, Berwyn, PA) had statistically significant clinical improvements. Changes in biomarkers of neurodegeneration and neuroinflammation were also observed. Posiphen is an orally administered translational inhibitor of neurotoxic proteins that form aggregates known to be pathophysiologic hallmarks of neurodegenerative disease.

Among participants with PD (n=54), those treated with posiphen vs placebo, at day 25, had a dose-dependent mean 2.43-point (13.4%) improvement on the Unified Parkinson Disease Rating Scale (UPDRS) compared with baseline (P<.01). Statistically significant improvements on the Wechsler Assessment of Intelligence Scale (WAIS)-coding subtest with posiphen vs placebo were also seen. A phase 3 trial of posiphen for PD is planned that will enroll participants with Hoehn & Yahr (HY) scores of 1 to 3 without PD-related psychosis or suicidal ideation. 

In participants with AD (n=14), those who received 80 mg posiphen vs placebo had a 4.4-point vs 1.1-point (P<.05) improvement on the Alzheimer Disease Assessment Subscale Cognitive subscale (ADAS-cog) over a 25-day treatment period. The improvement observed with posiphen treatment reflects a 30% improvement compared with baseline scores. On the WAIS-coding subtest, those who received posiphen had a 23% improvement, approximately 4 times that seen with placebo.

Maria L. Maccecchini, PhD, founder, president, and chief executive officer of Annovis, said, "We are pleased to have met primary, secondary, and exploratory endpoints in these studies. Our goal is to develop a treatment for neurodegenerative diseases that is safe, effective, and easy for patients to use and benefit from. We are also eager to provide patients in the mild to moderate stages a solution that change the course of their neurodegenerative disease." 

All participants had cerebrospinal fluid (CSF) analysis of multiple biomarkers. In participants with AD, phosphorylated tau and total tau levels were reduced as were amyloid precursor protein, and the ratio of amyloid β 42 to 40 ratio (Aβ42-40) ratio increased. Among participants with PD, α-synuclein levels decreased. Reductions in neuroinflammatory markers and biomarkers for neurodegeneration, neurofilament light and neurogranin, were also seen in both groups. As published in the journal Pharmaceutics, posiphen also decreases levels of another neurotoxic aggregrating protein, huntingtin, known to be causative of the neurodegenerative Huntington disease.  

In these trials, early AD was defined as a Mini Mental State Examination (MMSE) score of 18 to 28 and early PD as HY score 1 to 3.