ANVS401 Lessens Protein Buildup, Improves Cognition, Data Show

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by Patricia Inacio, PhD |

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Annovis Bio’s oral therapy ANVS401 lessened the accumulation of toxic forms of amyloid-beta and tau protein — two hallmarks of Alzheimer’s disease — and led to significant improvements in cognition in patients with early Alzheimer’s, data from a Phase 2a study show.

Moreover, ANVS401 levels in the blood were in agreement with previous studies and the therapy was deemed safe, meeting both primary and secondary trial goals.

It has also shown promising results for Parkinson’s disease (PD), improving patients’ motor and cognitive function.

“Meeting primary endpoints and the reversal of the toxic cascade combined with improvements in cognition and function are the foundation for us to ask the FDA for two meetings — one to move into two phase 3 clinical trials for AD and one to move into two phase 3 clinical trials for PD,” Maria Maccecchini, PhD, founder, president and CEO of Annovis, said in a press release.

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The results were shared in a presentation at the 14th Clinical Trials on Alzheimer’s Disease conference (CTAD), Nov. 9–12 in Boston.

The toxic accumulation of protein aggregates, or clumps, are a hallmark of diseases like Alzheimer’s and Parkinson’s. In Alzheimer’s, these clumps are composed of beta-amyloid and tau protein, while in Parkinson’s they’re of alpha-synuclein protein.

These toxic clumps impair nerve cells’ communication and axonal transport — the system responsible for transporting vital molecules and signals from one nerve cell to another — and often cause brain inflammation.

ANVS401, also known as Posiphen, is an oral medication that prevents all three proteins from being made, acting as a potential treatment for both conditions.

The ongoing Phase 2a study, (NCT04524351), is testing ANVS401 as a treatment for people with early Alzheimer’s and Parkinson’s.

The goal is to determine the safety and tolerability of this 25-day treatment and to determine changes in disease biomarkers and cognitive status.

The trial is divided into two parts. The results now reported pertain to part one, in which 14 Alzheimer’s and 14 Parkinson’s patients were randomly assigned to receive 80 milligrams of ANVS401 or a placebo daily for four weeks. The second part of the trial will investigate multiple doses of ANVS401.

Treatment with ANVS401 was well-tolerated and safe, and its pharmacokinetics profile (the movement of a medicine into, through, and out of the body) agrees with earlier human studies, with the trial meeting both primary and secondary goals.

ANVS401 also lessened the accumulation of toxic forms of beta-amyloid and tau protein in Alzheimer’s disease patients compared with a placebo. A reduction was also seen for alpha-synuclein protein accumulation in patients with Parkinson’s.

This was accompanied by a reduction of inflammation markers and improvements in axonal integrity and synapses (gaps between nerve cells that allow them to communicate with each other) in both patient groups.

Exploratory cognitive efficacy measures for Alzheimer’s patients — the Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-Cog11) and Wechsler Adult Intelligence Scale (WAIS) — were met, with ANVS401 treatment leading to significant improvements.

Compared with the start of the trial (baseline), after 25 days the ADAS-Cog11 score was improved by 4.4 points in patients treated with ANVS401 — a 30% statistically significant improvement. When compared with the placebo group, treatment with ANVS401 was better by 3.3 points, representing a 22% improvement.

In the WAIS test, which measures the speed of movement and thought, Alzheimer’s patients given ANVS401 showed a 23% statistically significant improvement compared with the baseline.

In Parkinson’s patients, treatment with ANVS401 also resulted in significant improvements in motor function and in speed of thinking.

According to Annovis, these findings agree with preclinical results from Alzheimer’s mouse models, where treatment with ANVS401 lessened the toxic accumulation of beta-amyloid by 5–20% and led to improvements in cognition and function.

“We believe we have begun to unravel the relationship between biomarker reduction and efficacy, a topic that has been a focus of research for some time. By comparing biomarker levels at fully effective doses of ANVS401 in both mice and humans suffering from AD [Alzheimer’s disease] and PD [Parkinson’s disease], we see that a small reduction in biomarkers and inflammatory markers is sufficient to lead to statistically significant improvements in outcomes,” Maccecchini said.