First Patients Dosed in Annovis Bio’s ANVS401 Trial, Delayed Due to COVID-19

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by Inês Martins PhD |

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ANVS401, Parkinson's and Alzheimer's

The first three patients have been dosed in a Phase 2a clinical trial investigating Annovis Bio‘s lead compound ANVS401 as a treatment for people with early Alzheimer’s and Parkinson’s diseases, the company said.

The trial (NCT04524351) will recruit up to 68 participants at 15 sites scattered across the U.S. Thus far, only the sites in Florida and Utah are open for enrollment; more information can be found here. The remaining sites are in high COVID-19 areas and will open when the disease is less rampant.

“While COVID-19 has previously delayed trials for most biopharma companies, including the start of this trial, having a diverse mix of study sites should afford us the opportunity to maintain recruitment and treatment schedules moving forward,” Maria Maccecchini, PhD, CEO of Annovis Bio, said in a press release.

Diseases like Alzheimer’s and Parkinson’s are characterized by the buildup of toxic protein aggregates, or clumps, that interfere with normal neuronal processes, including nerve cell communication, protein transport, and brain inflammation. This eventually causes the premature death of nerve cells.

In Alzheimer’s, both beta-amyloid and tau accumulate in the brain, while clumps of the alpha-synuclein protein are the hallmark of Parkinson’s. ANVS401 is an oral medication that prevents all three proteins from being made, acting as a potential treatment for both conditions.

In addition to lowering the brain levels of these proteins in humans and animals, ANVS401 — which also is known as Posiphen — was seen to restore memory and learning in Alzheimer’s mouse models and to lessen gut problems in models of Parkinson’s.

An ongoing Phase 2a trial called DISCOVER (NCT02925650) is investigating ANVS401 in people with early Alzheimer’s disease. Up to 24 participants will be enrolled and randomly assigned to receive one of three ANVS401 doses – 60 mg, 120 mg, or 180 mg – or a placebo.

The goal is to determine the safety and tolerability of this 23-25 day treatment, and to determine changes in disease biomarkers, cognitive and mental status, and neuropsychiatric symptoms.

While the Alzheimer trial is ongoing, ANVS401 has never been tested in people with Parkinson’s disease. The newly opened trial recently gained approval from a central institutional review board (IRB) to investigate this treatment in both conditions.

The trial will be conducted in two parts. First, 14 Alzheimer’s and 14 Parkinson’s patients will be enrolled and randomly assigned to receive ANVS401 at an 80 mg dose each day, or a placebo, for four weeks.

In addition to testing for safety and changes in functional impairment and cognition, this part of the trial also will serve to investigate biomarkers of the toxic cascade and neuronal cell death, and whether changes to such biomarkers are needed in part 2.

The second part of the trial will investigate multiple doses of ANVS401 in Parkinson’s patients, much like what’s being done in DISCOVER for those with Alzheimer’s. A total of 40 participants will be randomly assigned to receive ANVS401 at daily doses of 5 mg, 10 mg, 20 mg, or 40 mg.

The goal is to determine an optimal dose — the safest with the strongest efficacy — for this patient population. Initial data from this trial is expected in early 2021, and final data by late summer 2021.

“Beginning treatment in our second Phase 2a study is a major milestone for Annovis,” Maccecchini said. “This brings us one step closer to evaluating whether our approach may translate into a novel treatment option for patients suffering from a range of neurodegenerative diseases.”