ANAVEX 3-71 Meets Primary, Secondary End Points in Phase 1 Study

Christopher U. Missling, PhD

A phase 1 study of ANAVEX 3-71 (NCT04442945), an oral small molecule agonist of both SIGMAR1 and CHRM1 (Cholinergic Receptor Muscarinic M1), met its primary safety end point, as well as its secondary end point, Anavex Life Sciences recently announced. The drug is in development for treatment of neurodegenerative diseases and has previously been granted orphan drug designation by the FDA for treatment of frontotemporal dementia (FTD).¹

The double-blind, randomized, placebo-controlled trial evaluated the safety, efficacy, and pharmacokinetics (PK) of oral escalating doses of ANAVEX 3-71 in evaluating in healthy patients. Investigators concluded that the treatment, previously known as AF710B, was well tolerated in all cohorts receiving single doses, ranging from 5-200 mg daily. No serious adverse events or significant lab abnormalities were reported. The treatment showed linear PK, which was also dose proportional up to 160 mg and was unaffected by gender. Food was not found to have an effect the bioavailability of the treatment. 

“We are pleased with the phase 1 trial results for ANAVEX 3-71 and are eager to advance ANAVEX 3-71 into phase 2,” Christopher U. Missling, PhD, president and CEO, Anavex, said in a statement.¹ “These encouraging results provide a proof of concept of our SIGMAR1 product platform and helps validate Anavex’s approach to CNS target selection and drug discovery and increases Anavex’s confidence in the potential of our precision medicine technology to address serious neurodegenerative diseases.”

Meeting its secondary end point, the study also characterized the effect of ANAVEX 3-71 on electrocardiogram parameters, which were not clinically significant in any subject. Across all dose groups, participant QT interval corrected for heart rate by Fredericia’s cube root formula measures were normal, with no differences observed between treatment and placebo groups. 

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The study included a total of 42 men and women between the age of 18-35 years who were given up to 4 single escalating doses of ANAVEX 3-71 or placebo, administered orally over a 30-day period. Participants were divided into 3 cohorts, the first receiving 5-50 mg oral doses of ANAVEX 3-71, the second receiving 55-200 mg, and the third receiving placebo. Participants were required to be non-smokers, have a body mass index of 19-28 kg/m2, have a body weight of 60-120 kg, and be in generally good health at the time of screening. Women were required to be of non-childbearing potential or using contraception. 

Based on the positive topline results from phase 1, Anavex plans to evaluate the treatment in a biomarker-driven clinical development dementia program for the treatment of FTD, as well as schizophrenias and Alzheimer disease. The study will be a quasi-basket trial and is anticipated to being in 2022 and will evaluate longitudinal effects of the treatment. 

“In addition to biomarkers…we would like to look at the neurofilament light change, NFL,” Edward Hammond, MD, MPH, PhD, chief medical officer, Avanex Life Sciences, said during a webcast conference call discussing the topline results.² “We will also look at plasma and serum concentrations of glutamate and other related amino acids. We are looking at TDP43, GRP78 concentrations as well, so it is quite a comprehensive biomarker strategy that will be able to demonstrate the effect of 3-71 on these pathologies, in order to give confidence going into further development.”

REFERENCES
1. Anavex Life Sciences reports positive results from phase 1 clinical trial. Avanex Life Sciences. January 10, 2022. Accessed January 11, 2022. https://www.anavex.com/post/anavex-life-sciences-reports-positive-results-from-phase-1-clinical-trial-of-anavex-3-71
2. Anavex 3-71 Phase 1 Top Line Data Conference Call. Anavex website. January 10, 2022. Accessed January 11, 2022. https://www.anavex.com/anavex3-71phase1toplinedataconferencecall