ANVS401 Improves Cognition in Alzheimer’s and Parkinson’s, Data Show

Annovis Bio’s oral therapy ANVS401 (also known as Posiphen) led to significant improvements in cognition in patients with Alzheimer’s disease, according to data from the first patient group in a Phase 2a study.

The improvements were also observed in patients with Parkinson’s disease enrolled in the study.

“The results from the first cohort of 14 [Alzheimer’s] and 14 [Parkinson’s] patients, show that the drug is effective in both diseases,” Maria L. Maccecchini, PhD, CEO of Annovis Bio, said in a press release.

The toxic accumulation of protein aggregates, or clumps, are a hallmark of diseases like Alzheimer’s and Parkinson’s. This accumulation can impair several neuronal processes, including nerve cell communication and axonal transport — the system responsible for transporting vital molecules and signals from one nerve cell to another. It can also induce brain inflammation. All these factors can eventually cause the premature death of nerve cells.

In Alzheimer’s, the proteins beta-amyloid and tau accumulate in the brain, while clumps of the alpha-synuclein protein are seen in Parkinson’s patients. ANVS401 is an oral medication that prevents the production of all three proteins. Thus, it is thought to be able to improve axonal transport, prevent the death of nerve cells, and reduce brain inflammation.

An ongoing Phase 2a study (NCT04524351) — which is still recruiting participants across multiple sites in the U.S. — is testing ANVS401 as a treatment for people with early Alzheimer’s and Parkinson’s. The trial is divided in 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 25 days.

Samples of blood and cerebrospinal fluid, the fluid that bathes the central nervous system (brain and spinal cord), were collected from each participant. Analysis for specific biomarkers of nerve cell death and loss of function is currently underway.

Despite not being powered to assess efficacy, the results so far showed that, compared to the start of the trial (baseline), Alzheimer’s patients treated with ANVS401 for 25 days experienced statistically significant improvements in cognition, as measured by the Alzheimer’s Disease Assessment Scale–Cognitive Subscale 11 (ADAS-Cog11) — an established test to assess cognition in Alzheimer’s patients.

The cognitive abilities of ANVS401-treated patients improved significantly by 30% — corresponding to 4.4 points on the ADAS-Cog11 scale — relative to baseline. When compared to patients in the placebo group, the improvement was 22% — corresponding to 3.3 points on the ADAS-Cog11 scale.

The improvements in cognition extended to patients with Parkinson’s disease who received ANVS401, as measured by the Unified Parkinson’s Disease Rating Scale (UPDRS). 

“We set up this study to measure the toxic cascade leading to nerve cell death and loss of function and its reversal in [Alzheimer’s] and [Parkinson’s],” Maccecchini said. “Since the study was powered to investigate changes in biomarker levels, not to demonstrate efficacy, we believe these results are that much more impactful.”

Importantly, axonal transport was normalized after treatment with ANVS401.

“The toxic cascade in neurodegeneration begins with high levels of neurotoxic proteins, which impair axonal transport, increase inflammation and eventually lead to nerve cell death and permanent loss of cognition and function,” Maccecchini said. “Seeing efficacy in both patient populations supports our hypothesis that the impairment of axonal transport, the information highway of the nerve cell, affects nerve cells in the same way in both diseases.”

No adverse events were linked to the treatment in this trial, in agreement with the previously reported safety profile of ANVS401.

The second part of the trial will investigate multiple doses of ANVS401 in Parkinson’s patients. A total of 40 participants were randomly assigned to receive ANVS401 at daily doses of 5, 10, 20, or 40 milligrams. The goal is to determine an optimal dose — the safest dose with the strongest efficacy — for this patient population.

The complete results of the trial are expected by July or August, after which Annovis Bio will request a meeting with the U.S. Food and Drug Administration to discuss the results, as well as additional preclinical data.

The company expects to advance ANVS401 to late-clinical stage by the end of the year, but this is dependent on the results of the ongoing Phase 2 trial.