Zoals te zien is dit een wat ouder artikel dat ik vond op de site van AlzheimerNews Today( AMERIKAANS PLATFORM) Ik ken die site nog niet zo lang en vind het een prima samenvatting van de VIVO's stand van zaken:
News
2 Trials Testing Oral Varoglutamstat Now Enrolling in US, Europe
Patricia Inacio PhD avatar
by Patricia Inacio PhD | November 1, 2021
Vivoryon Therapeutics is looking to enroll patients at different stages of Alzheimer’s disease for two ongoing, Phase 2 trials evaluating the safety and efficacy of its investigational oral treatment varoglutamstat.
The therapy candidate has shown evidence, in earlier trials, of improving cognition, memory, and attention in Alzheimer’s patients, with “encouraging results after only 12 weeks of treatment,” the company said in a press release.
The first trial, a Phase 2b study called VIVIAD (NCT04498650), is currently underway at a dozen clinical sites in Denmark, Germany, and the Netherlands. It is aiming to recruit 250 patients with mild cognitive impairment and mild dementia due to Alzheimer’s. Information on enrollment is available here.
Due to the COVID-19 pandemic and to avoid recruitment delays, additional clinical sites have been added in Germany and the Netherlands. Up to 10 more sites in Spain and Poland will be joining the study over the next weeks, the company said.
A complementary study — the first in the U.S. testing varoglutamstat — is underway at the University of California San Diego (UCSD) School of Medicine, under the coordination of the Alzheimer’s Disease Cooperative Study (ADCS). That Phase 2a/b study is called VIVA-MIND (NCT03919162).
RECOMMENDED READING
Aduhelm approval
June 17, 2021 News by Hawken Miller
Aduhelm Approval Greeted With Joy, Concern in Alzheimer’s Community
Its initial enrollment target is 180 patients, with early stages of Alzheimer’s disease. More information is available on the trial page. Eight additional clinical sites, which have already received regulatory approval, according to the company, are expected to join soon.
“We are following a diligently designed development strategy and making continued progress towards overcoming the challenges of drug development in AD [Alzheimer’s disease], moving varoglutamstat through clinical development as efficiently as possible,” said Ulrich Dauer, PhD, CEO of Vivoryon.
Alzheimer’s disease is characterized by amyloid plaques and tau tangles — clumps of two proteins that accumulate to toxic degrees inside brain neurons — that cause nerve cell death.
Varoglutamstat (PQ912), a small molecule taken as an oral pill, is able to block the activity of an enzyme called glutaminyl cyclase. This enzyme is present at abnormally high levels in the brains of Alzheimer’s patients and is known to play a role in the formation of a particularly toxic form of amyloid-beta, called the N3pE amyloid. Amyloid-beta is the protein that clumps into the toxic plaques that characterize Alzheimer’s.
N3pE amyloid acts as a seeding factor, promoting the aggregation, or clumping, of amyloid-beta; its levels correlate with cognitive decline.
Contrary to other therapeutics that work to reduce the levels of these amyloid-beta plaques, varoglutamstat — which targets N3pE amyloid — may act earlier and prevent their formation, according to Vivoryon.
Also, since glutaminyl cyclase is important for the stability and activity of the pro-inflammatory CCL2 protein, which also promotes tau protein aggregates — another hallmark of Alzheimer’s disease — varoglutamstat holds the potential to lessen neuroinflammation and cognitive decline.
In a first-in-human Phase 1 trial, which involved 205 healthy volunteers, varoglutamstat was found to be well-tolerated. In the subsequent SAPHIR Phase 2a trial (NCT02389413), with 120 patients in the early stages of Alzheimer’s, treatment with varoglutamstat, twice daily for 12 weeks, or about three months, was deemed safe.
Moreover, exploratory efficacy measures in the SAPHIR trial supported the therapy’s potential to lessen disease hallmarks — and to enhance nerve cell communication and improve patients’ cognition, memory, and attention.
Based on these findings, the company then launched the two clinical trials underway in Europe and the U.S.
“Based on its mechanism of action and encouraging data from earlier clinical studies, we believe that varoglutamstat is differentiated from other drugs in development, with potential benefits as an oral agent, potentially reduced side effects, and cost, which would make it accessible to a large number of [Alzheimer’s] patients who are anxiously waiting for new treatment options,” said Howard Feldman, MD, director of the ADCS at UC San Diego, and the U.S. trial’s director.
In the VIVIAD Phase 2b study, in Europe, the first 90 patients will be randomly assigned to receive either varoglutamstat — at doses of 300 or 600 miligrams (mg) — or a placebo, given twice daily for 24 weeks, or about six months.
This will be followed by an interim analysis to evaluate the treatment’s safety and efficacy, and to determine the best dose of varoglutamstat for further trials. The remaining patients will then be treated with the selected dose of varoglutamstat, twice daily, or a placebo for a minimum of 48 weeks (about one year) and up to 96 weeks (close to two years).
The primary goal of the VIVIAD trial is to determine the therapy’s safety and cognitive efficacy assessed by the neuropsychological test battery (NTB) throughout the study period. Additional exploratory goals include cognitive tests, and functional electroencephalograms and MRI scans, as well as the evaluation of disease markers in the cerebrospinal fluid, which surrounds the brain and spinal cord.
The therapy’s long-term safety and tolerability, as well as its efficacy on brain activity, cognition, and activities of daily living, will be assessed as secondary goals.
The first interim results of the trial are expected by June 2022, and the final results by the end of 2023, according to the developer.