First Patients Dosed in Clinical Trial Investigating ANVS401 as Treatment for Parkinson’s and Alzheimer’s

The first three patients have been dosed in a Phase 2a clinical trial investigating the safety and effectiveness of ANVS401, Annovis Bio’s lead compound designed as a potential treatment for Parkinson’s and Alzheimer’s diseases.

The launch of the Phase 2a trial (NCT04524351) marks the second such study investigating ANVS401, and the first to enroll patients with Parkinson’s disease. Annovis expects to share initial data in early 2021 and final data by late summer 2021.

The trial is currently recruiting and information about eligibility and locations is available here.

“Beginning treatment in our second Phase 2a study is a major milestone for Annovis,” Maria Maccecchini, PhD, CEO of Annovis, said in a press release. “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.”

The progression of both Parkinson’s and Alzheimer’s disease involves the buildup and aggregation of toxic proteins in the brain. In Parkinson’s, the protein that aggregates (clumps together) is called alpha-synuclein; in Alzheimer’s, it is the beta-amyloid and tau proteins.

These protein aggregates can disrupt communication between nerve cells in the brain, disrupting normal function and eventually leading to cell death.

ANVS401, which also is known as Posiphen, is designed to block the production of all three proteins, acting as a potential first treatment for both Parkinson’s and Alzheimer’s. The medication inhibits a process known as translation, the final step of protein production in which a messenger RNA transcript of a gene is “read” and transformed into a protein.

Pre-clinical in vitro (in the lab) studies using human and mouse cells have shown that toxic protein levels decreased following exposure to treatment.

Furthermore, pre-clinical studies using two mouse models found that gastrointestinal symptoms associated with early Parkinson’s eased significantly after treatment with ANVS401.

According to Annovis, ANVS401 reduced the levels of neurotoxic proteins, improved nerve cell communication, lowered inflammation, and restored healthy nerve cells in both Alzheimer’s and Parkinson’s mice.

Annovis patented the ANVS401 treatment in February, and received approval in July to launch the new Phase 2a study from a central institutional review board (IRB).

The study will enroll a total of 68 patients at 15 sites across the U.S., including 28 with either early stage Parkinson’s or Alzheimer’s (14 of each) for the first part of the trial, and another 40 patients with early Parkinson’s disease for the second part.

The first part will evaluate the safety and effectiveness of daily 80 mg ANVS401 capsules over a 28-day treatment course, with some patients receiving the treatment and others receiving a placebo for comparison.

Enrolled patients will be required to make clinical visits at the beginning and end of the treatment period to monitor for adverse reactions to the treatment, evaluate motor symptoms, and collect blood and cerebrospinal fluid (the liquid that surrounds the brain and spinal cord, CSF) for analysis.

The second part of the study will compare different doses of ANVS401 by randomly assigning 10 Parkinson’s patients into four dosage groups — 40 mg, 20 mg, 10 mg, 5 mg — and monitoring safety and effectiveness between them.

With the launch of the new clinical trial, Annovis is taking precautions with regard to the COVID-19 pandemic by spreading testing sites geographically, and opening testing sites only in regions with lower incidence rates of the virus.

“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,” said Maccecchini.

Another ongoing Phase 2 DISCOVER clinical trial (NCT02925650) is evaluating the safety, tolerability, and effectiveness of ANVS401 in 24 patients with early Alzheimer’s disease, and currently is recruiting participants.