Phase 2 Trial of Cognitive Treatment NYX-458 Resumes

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by Diana Campelo Delgado |

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Aptinyx‘s Phase 2 clinical trial evaluating its investigational oral compound NYX-458 for the treatment of cognitive impairment and mild dementia associated with Parkinson’s disease is resuming patient screening after a temporary pause due to the COVID-19 pandemic.

Recruitment is underway at multiple locations in the United States. More information and contacts is available here.

“We are pleased to be moving forward in evaluating NYX-458 in patients suffering from cognitive impairment,” Norbert Riedel, PhD, CEO of Aptinyx, said in a press release.

NYX-458 is an oral small molecule compound that regulates the activity of N-methyl-D-aspartate (NMDA) receptors in the brain. These receptors are essential for nerve cell communication, which occur at structures called synapses located at the junction between nerve cells.

Parkinson’s damages dopamine-producing neurons in the brain. One of dopamine’s many functions is to regulate NMDA receptors, and its loss is believed affect their regulation and, subsequently, cognition.

By controlling NMDA receptor activity, NYX-458 may help to ease or reverse cognitive impairment associated with Parkinson’s.

“Modulation of NMDA glutamate receptors to address this underlying disease pathology is a compelling approach to treating the broad spectrum of symptoms associated with cognitive impairment,” said Peter LeWit, MD, professor of neurology at Wayne State University School of Medicine, Detroit, Michigan.

The ongoing Phase 2 trial (NCT04148391) is evaluating the safety and tolerability of oral NYX-458 compared to a placebo. The study seeks to enroll about 100 people ages 50 to 80 who have mild cognitive impairment or mild dementia associated with Parkinson’s disease, or prodromal dementia (before symptoms occur), or manifest dementia with Lewy bodies,.

Patients will be assigned randomly to receive an oral daily dose of 10 mg, 30 mg, or 100 mg of NYX-458, or a placebo, for 12 weeks. Those completing this part of the study then may enter a two-week follow-up period.

In this study, researchers will assess how the therapy affects patients’ memories, attention, executive functions, visuospatial deficits, and quality of life.

This Phase 2 trial was supported by positive preclinical data in a non-human primate model of Parkinson’s disease. In these animals, NYX-458 was seen to significantly increase attention, improve cognitive flexibility, and enhance working memory as quickly as one day after the administration of a single oral dose.

The therapy was investigated previously in a placebo-controlled Phase 1 clinical trial in 62 healthy volunteers who were given NYX-458 in ascending doses ranging from 10 mg to 200 mg. Results reported by Aptinyx showed a good safety profile with no treatment-related adverse side effects reported.

“We believe the mechanism of NYX-458 is uniquely suited to address the cognitive deficits experienced by these patients and we look forward to building on the compelling preclinical data we have garnered with NYX-458 to date,” added Riedel.

Results of the ongoing Phase 2 trial are expected in the second half of 2022.

“I look forward to seeing the data from this study, which offers a first step in understanding the potential for NYX-458 as a novel therapeutic option,” LeWitt said.