Interim Trial Data Hints at Efficacy of ANVS401

ANVS401, an investigational therapy for neurodegenerative diseases being developed by Annovis Bio, improved the speed and coordination of people with Parkinson’s disease in a Phase 2a clinical trial, an interim analysis suggests.

“The results from this interim analysis are very encouraging. 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,” Maria L. Maccecchini, PhD, the CEO of Annovis, said in a press release.

Several neurodegenerative diseases are characterized by the formation of abnormal protein aggregates (clumps) in the brain, with toxic effects on brain tissue. For example, Parkinson’s is characterized by aggregates of a protein called alpha-synuclein.

ANVS401, also known as Posiphen, is intended to halt the production of these toxic protein aggregates by interfering with translation — the process by which proteins are made in cells. Pre-clinical data from Parkinson’s mouse models have indicated that the therapy can ease gut-related symptoms.

The new interim analysis uses data from an ongoing clinical trial (NCT04524351) that is testing the investigational medication in people with early Parkinson’s or Alzheimer’s diseases. Participants are given one of several doses of ANVS401, or a placebo, taken by mouth once daily for 25 days.

The Annovis-sponsored trial is currently recruiting participants at multiple locations in the U.S.; additional information is available here.

This interim analysis includes data from the first 14 Parkinson’s patients who have completed treatment; nine were given ANVS401, and five received placebo.

The trial’s main goal is to determine the safety of the investigational medication, as determined by the occurrence of adverse events (side effects). So far, the interim analysis is consistent with prior safety data; the medication appears safe at a dose of 80 mg once a day in humans.

Only one potentially treatment-related adverse event — mild dizziness — has been reported in the trial. It was reported by only one participant, who was given the placebo.

The new analysis shows that, in one test that measures speed of execution, treatment with ANVS401 significantly improves scores among Parkinson’s patients. The difference was significant both in comparisons to the placebo group, and to the patients’ values at baseline (the start of the study, before treatment).

On another test that measures coordination, treatment with ANVS401 led to an improvement that was not statistically significant.

Annovis did not provide details about the exact tests used to measure speed or coordination.

On the MDS-UPDRS — a Parkinson’s-specific test that measures the severity and progression of disease — individuals given placebo either stayed the same  or got worse. In contrast, MDS-UPDRS scores among participants given ANVS401 either stayed the same or improved.

Additional analyses looking at biological samples (blood and cerebrospinal fluid) taken from the trial participants are ongoing.

“We set up this study to measure the toxic cascade leading to nerve cell death and loss of function and its reversal. The study was powered to investigate a difference of 20 to 25 percent in biomarker levels, not to demonstrate efficacy, making this data that much more significant,” Maccecchini said.

Upon completion of the Phase 2a trial, the company will request a meeting with the U.S. Food and Drug Administration to present clinical and pre-clinical data, which hopefully can advance ANVS401 into late-stage studies by the end of this year.

Annovis was issued a U.S. patent for ANVS401 last year. The company also is running another trial, called DISCOVER (NCT02925650), which is testing ANVS401 in people with early Alzheimer’s disease.