Buntanetap Safe With Signals of Efficacy for Alzheimer Disease and Phase 3 Trials Are Being Initiated

In a phase 2 trial (NCT04524351) in people with early Alzheimer disease (AD) or Parkinson disease (PD) treatment with 5 to 80 mg/day oral buntanetap (ANVS401; Annovis, Berwyn, PA) for 25±2 days had no adverse events. These results are consistent with the ascending dose study in which side effects did not occur at doses less than 160 mg/day (nausea and vomiting in 36% of participants).

Participants in this and planned future studies are able to continue taking concomitant treatments for AD. Early AD was defined as having a score of 0.5 to 1 on the Clinical Dementia Rating Scale (CDR) and 18 to 28 on the Mini-Mental State Examination (MMSE).

Those with AD treated with buntanetap had a mean improvement of approximately 30% on the Alzheimer Dementia Assessment Scale-Cognition (ADAS-Cog) scale. A 23% improvement on the Symbol Digit Coding Test (SDCT), a measure of working memory and processing speed, was also observed. Both improvements were several times larger than with placebo, although the cohort of people with AD in this phase 2 safety trial was too small for statistically significant comparisons to be made. Plans for a phase 3 trial on buntanetap for AD are under review by the Food and Drug Administration (FDA), and it is hoped enrollment will begin in the fourth quarter of 2022. 

In those with PD, who comprised a larger cohort of 54 participants, statistically significant improvements on the Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and the SDCT both occurred. A phase 3 trial in people with early PD has begun enrollment and the first participant has received a dose.

Maria Maccecchini, PhD founder and chief executive of Annovis said, "We are pleased with the safety seen in our phase 1 and 2 clinical trials and grateful to all the participants in those trials. It is exciting to see strong signals of treatment effects across multiple neurodegenerative diseases, which speaks to the power of targeting translation of multiple neurotoxic misfolded proteins, potentially providing a multimodal approach with a single daily oral treatment. The interest in our phase 3 trial in PD has been high, with over 150 people applying for screening just a few weeks after the trial was approved, and we hope to have similarly high interest from the AD community when that phase 3 trial begins." 

Buntanetap, previously known as posiphen, is a novel drug with a unique mechanism of action targeting multiple proteins implicated in neurodegenerative diseases, including amyloid β, tau, α-synuclein, and TDP43. When misfolded, all of these proteins aggregate and impair axon transport, resulting in neuronal cell death. Buntanetap binds a conserved loop region of mRNA in these neurotoxic proteins to prevent translation (production) of misfolded proteins.