Exploratory Phase 2 Results of Combination Oral Therapy for Alzheimer’s Justify Further Study

Pharnext  is reporting positive Phase 2 results from its investigative pleodrug PXT-864, a new oral combination of existing therapies, for the treatment of Alzheimer’s disease. Results from the exploratory study were presented at the 9^th Clinical Trials on Alzheimer’s Disease (CTAD) meeting, held recently in San Diego.

PLEODIAL-I (NCT02361424) was a Phase 2, 12-week preliminary efficacy study of several doses of PXT-864 (a fixed combination of acamprosate and baclofen at low dose) in 45 treatment-naive patients with mild AD, accessing the drug’s safety and possible effects on cognitive impairment. Patients received the active drug for four weeks, followed by four weeks of placebo, and, finally, another four weeks with PXT-864. Patients then moved to PLEODIAL-II (NCT02361242) for another 24 weeks, and continued on their prior PXT-864 dose. During the last 12 weeks of this study, they were co-treated with donepezil 5 mg.

Results presented showed that treatment with PXT-864 was safe and well-tolerated, with no serious adverse reactions observed. Data also suggested that the drug may slow progression of cognitive disability in mild AD patients, as measured by decline in the AD Assessment Scale Cognitive Subscale test (ADAS-Cog-11). Researchers reported that pooled data from PXT864-treated patients, as compared to historical placebo, appeared to show lesser decline.

PXT-864 use alongside donepezil 5mg daily was also found to be safe, and the co-treatment “pointed toward” cognitive improvements or at least a stabilized ADAS-Cog-11 score at week 36, the presentation reported.

Pharnext is now planning future clinical trials, including an international multicenter adaptive-design Phase 2 study.

“We believe that these findings bring new evidence of PXT864 safety and efficacy in patients suffering from mild stages of Alzheimer’s disease and this clinical trial has the potential to be a key turning point in the effort to finally provide an efficacious treatment for these patients,” Daniel Cohen, MD, PhD, co-founder and chief executive officer of Pharnext, said in a press release. “These data also further validate our PLEOTHERAPY^© research and development approach and we hope to provide novel treatments for many diseases via such synergic drug combinations.”

PXT864, using the company’s Pelotherapy approach, combines two approved drugs — acamprosate (calcium acetylhomotaurinate; brand name, Campral) and baclofen (also, chlorophenibut; brand names include Kemstro). The investigative pleodrug thought to address Alzheimer’s symptoms by synergistically protecting neurons and endothelial structures against amyloid-beta (Aβ) oligomers, which is thought to be the disease’s cause. The company is also planning to advance PXT864 in other neurodegenerative diseases, including Parkinson’s disease and amyotrophic lateral sclerosis (ALS).

“The data presented provide encouraging evidence for PXT864 as an entirely new approach in the treatment of Alzheimer’s disease,” said René Goedkoop, chief medical officer of Pharnext. “Today there are no treatments capable of altering the progressive course of this terrible disease. We look forward to the continuation of PXT864 clinical development and hope that we can bring an efficacious treatment to people suffering from Alzheimer’s disease and to improve their quality of life.”