In Neurodegenerative diseases
A Novel Approach in Neurodegenerative Diseases

PXT864 is a novel fixed-dose synergistic combination of baclofen and acamprosate formulated as a pill given twice a day. PXT864’s assumed main mechanism of action in neurodegenerative diseases is the restoration of balance between excitatory (glutamate activity) and inhibitory (GABA activity) pathways, disrupted by toxic factors such as Aβ oligomeric peptides in Alzheimer’s disease. 
PXT864 showed positive safety and tolerability results in a Phase 1 clinical trial that enrolled 24 healthy volunteers. 
PXT864’s most advanced indication is Alzheimer’s disease. An additional Phase 1 clinical trial, which enrolled 20 healthy volunteers, showed initial efficacy in a scopolamine dementia-induced model. PXT864 has also generated encouraging results in a Phase 2a clinical trial completed in 2015 in 45 patients with mild Alzheimer’s disease (see more details below). PXT864 clinical development in this indication will be further advanced through partnerships. 

The overlapping genetic, molecular, and cellular characteristics of Alzheimer’s disease and Amyotrophic Lateral Sclerosis (ALS) supported investigating the potential effectiveness of PXT864 in this latter indication. PXT864 has generated encouraging results in several preclinical ALS models (Boussicault et al. J Neurosci Res. 2020). Based on previous Phase 1 safety and tolerability results, PXT864 alone or associated with already approved drugs in ALS is ready to start its clinical development in Phase 2a clinical trial. 

Encouraging Results from an Exploratory Phase 2a clinical trial in Alzheimer’s disease

The PLEODIAL™ trial was an exploratory multicenter single-blind Phase 2a study that evaluated 3 doses of PXT864 in 45 patients with mild Alzheimer’s disease who were naïve to anti-dementia treatment: the first two doses were based on the same ratio of baclofen / acamprosate [dose 1 and 2] and the third dose used another ratio [dose 3].

The main objectives were to assess safety, compliance and preliminary efficacy on cognitive and behavioral impairment. The study was designed over a period of 36 weeks: “PLEODIAL-I” for the first 12 weeks followed by “PLEODIAL-II” for the remaining 24 weeks. During PLEODIAL-I, patients received PXT864 during the first 4 weeks (“challenge”) followed by 4 weeks of placebo (“de-challenge”) and then 4 weeks of PXT864 (“re-challenge”). During PLEODIAL-II, patients were invited to continue on PXT864 with the dose they had received during PLEODIAL-I.

During the last 12 weeks of the study, physicians were authorized to co-administrate donepezil 5 mg with PXT864. In total, patients were treated with PXT864 for 32 out of 36 weeks in the PLEODIAL-I and II studies. This clinical trial was conducted in 7 French memory centers from February 2013 to December 2015.

Data collected suggests that:

  • PXT864 is well tolerated and safe for use in patients with Alzheimer’s disease
  • PXT864 may slow the progression of cognitive disability in patients with mild Alzheimer’s disease
  • PXT864 may be used concomitantly with low-dose donepezil treatment (5 mg daily).

These findings show promising preliminary efficacy of PXT864 and potential use at higher doses to demonstrate a sustained therapeutic effect on Alzheimer’s disease. It could also be combined with already approved drugs in Alzheimer’s disease or with other new chemical entities to create novel new entity. This needs to be further explored in future studies through partnerships.

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