Buntanetap Shows Safety, Efficacy in Phase 2a Trial; More Planned
This was according to data from a Phase 2a trial (NCT04524351) that evaluated the investigational therapy against a placebo in 15 people with early Alzheimer’s.
Supported by these findings, buntanetap’s developer, Annovis Bio, is planning three more placebo-controlled studies of the treatment, including a three-month dose-finding trial and two long-term trials (12 and 18 months) in early and moderate Alzheimer’s patients.
Annovis presented the findings in a presentation titled, “Translational Inhibition of Multiple Neurotoxic Proteins Leads to Improved Cognition in Alzheimer’s Disease,” at the Alzheimer’s Association International Conference 2022.
Previously known as ANVS401 or posiphen, buntanetap is being developed for Alzheimer’s and Parkinson’s disease.
It aims to lower levels of proteins that form insoluble, toxic clumps in the nerve cells of people with these neurodegenerative diseases. In Alzheimer’s disease, such proteins include amyloid-beta and tau.
Buntanetap protects against these clumps by inhibiting their translation, the process by which information in DNA is converted to produce a functional protein.
According to Annovis, buntanetap reduced inflammation and protected against nerve cell death in animal models, leading to fully restored function in seven different ones, including Alzheimer’s and Parkinson’s.
The investigational treatment has so far proven safe in more than 200 people, including healthy volunteers and neurodegenerative disease patients.
The Phase 2a study was divided into two parts. In part one, 15 people with Alzheimer’s and 14 with Parkinson’s were randomly assigned to receive oral buntanetap (80 mg) or a placebo once daily for 25 days. Ten Alzheimer’s patients were given buntanetap and five received a placebo. The second part of the trial investigated multiple doses of ANVS401 in 40 early-stage Parkinson’s patients.
Results showed the treatment was safe, meeting the trial’s primary goal. It also reached levels in the bloodstream that were expected based on earlier studies, meeting the trial’s secondary goal.
Levels of amyloid-beta and tau were significantly lowered in Alzheimer’s patients relative to those who received a placebo. The treatment also improved the integrity and function of nerve cell projections and reduced inflammation, Annovis stated.
The Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) and Wechsler Adult Intelligence Scale (WAIS) were used to evaluate the treatment’s effectiveness.
Compared with data from the study’s start, patients treated with buntanetap experienced a 4.4 point improvement in ADAS-Cog11 scores. Compared with the placebo group, treated patients showed a statistically significant 22% improvement. Similarly, treated patients experienced a 23% improvement in the WAIS test compared with the study’s start.
In Parkinson’s patients, buntanetap was similarly effective, leading to a lower accumulation of the toxic alpha-synuclein protein and significant improvements in cognition.
The ongoing DISCOVER study (NCT02925650) is evaluating the effects of multiple daily doses of buntanetap against a placebo in 19 patients with early Alzheimer’s, ages 55-89.
Participants are given oral capsules containing either 60, 120, or 180 mg buntanetap — or a placebo — three times a day for 23–25 days. The study’s primary outcomes include its safety and pharmacokinetics, the movement into, through, and out of the body.
The synthesis rate of a toxic form of amyloid beta in the cerebrospinal fluid — the fluid surrounding the brain and spinal cord — will also be measured. The feasibility of that measurement technique, along with Alzheimer’s biomarkers and cognition, are among the study’s secondary outcomes.
The DISCOVER study is expected to conclude in December.